Zhao Z

References (70)

Title : Rivastigmine Nasal Spray for the Treatment of Alzheimer's Disease: Olfactory Deposition and Brain Delivery - Guo_2024_Int.J.Pharm__123809
Author(s) : Guo H , Wang G , Zhai Z , Huang J , Huang Z , Zhou Y , Xia X , Yao Z , Huang Y , Zhao Z , Wu C , Zhang X
Ref : Int J Pharm , :123809 , 2024
Abstract : Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F(2) (containing 1% (w/v) viscosity modifier Avicel(a) RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F(2) exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.
ESTHER : Guo_2024_Int.J.Pharm__123809
PubMedSearch : Guo_2024_Int.J.Pharm__123809
PubMedID: 38224760

Title : The cholinergic pathway transmits signals of neuropeptide F to regulate feeding of Ostrinia furnacalis larvae - Jiang_2023_Pest.Manag.Sci__
Author(s) : Jiang X , Shi J , Yang H , Zhao Z
Ref : Pest Manag Sci , : , 2023
Abstract : BACKGROUND: Feeding is the basis of animal survival and reproduction. In insects, the neuropeptide F (NPF), a homologous polypeptide of NPY in vertebrates, plays an important role in regulation of feeding behavior. However, relatively little has been known about the molecular mechanism of feeding. RESULTS: In this study, we show that the cholinergic pathway is very important in signaling transmission of NPF feeding regulation in Ostrinia furnacalis larvae, in which the choline acetyltransferase (ChAT), the vesicular acetylcholine transporter (vAChT) in presynaptic membrane and the nicotinic acetylcholine receptor (nAChR) in postsynaptic membrane are positively regulated by NPF, while the ace1 and ace2 encoding the acetylcholinesterase (AChE) are negatively regulated by NPF, leading to a balance of acetylcholine (ACh) - the excitatory transmitter. More, the cholinergic pathway further transmits signaling to the downstream pathways of the phosphoInositide-3 kinase (PI3K) and the cAMP responsive element binding protein (CREB), respectively. CONCLUSION: The cholinergic transmission, positively regulated by NPF, is involved in feeding of O. furnacalis larvae via downstream PI3K and the CREB pathways, respectively. The deexcitation of cell cholinergic pathway or inhibition of PI3K and CREB lead to decreases of larval feeding amount.
ESTHER : Jiang_2023_Pest.Manag.Sci__
PubMedSearch : Jiang_2023_Pest.Manag.Sci__
PubMedID: 37183359

Title : A Dual Fluorescence Assay Enables High-Throughput Screening for Poly(ethylene terephthalate) Hydrolases - Liu_2023_ChemSusChem_16_e202202019
Author(s) : Liu K , Xu Z , Zhao Z , Chen Y , Chai Y , Ma L , Li S
Ref : ChemSusChem , 16 :e202202019 , 2023
Abstract : The drastically increasing consumption of petroleum-derived plastics hasserious environmental impacts and raises public concerns. Poly(ethylene terephthalate) (PET) is amongst the most extensively produced synthetic polymers. Enzymatic hydrolysis of PET recently emerged as an enticing path for plastic degradation and recycling. In-lab directed evolution has revealed the great potential of PET hydrolases (PETases). However, the time-consuming and laborious PETase assays hinder the identification of effective variants in large mutant libraries. Herein, we devise and validate a dual fluorescence-based high-throughput screening (HTS) assay for a representative IsPETase. The two-round HTS of a pilot library consisting of 2850 IsPETase variants yields six mutant IsPETases with 1.3-4.9 folds improved activities. Compared to the currently used structure- or computational redesign-based PETase engineering, this HTS approach provides a new strategy for discovery of new beneficial mutation patterns of PETases.
ESTHER : Liu_2023_ChemSusChem_16_e202202019
PubMedSearch : Liu_2023_ChemSusChem_16_e202202019
PubMedID: 36511949

Title : Variation in the HSL Gene and Its Association with Carcass and Meat Quality Traits in Yak - Wang_2023_Animals.(Basel)_13_
Author(s) : Wang X , Qi Y , Zhu C , Zhou R , Ruo Z , Zhao Z , Liu X , Li S , Zhao F , Wang J , Hu J , Shi B
Ref : Animals (Basel) , 13 : , 2023
Abstract : Hormone-sensitive lipase (HSL) is involved in the breakdown of triacylglycerols in adipose tissue, which influences muscle tenderness and juiciness by affecting the intramuscular fat content (IMF). This study analyzed the association between different genotypes and haplotypes of the yak HSL gene and carcass and meat quality traits. We used hybridization pool sequencing to detect exon 2, exon 8, and intron 3 variants of the yak HSL gene and genotyped 525 Gannan yaks via KASP to analyze the effects of the HSL gene variants on the carcass and meat quality traits in yaks. According to the results, the HSL gene is highly expressed in yak adipose tissue. Three single nucleotide polymorphisms (SNPs) were identified, with 2 of them located in the coding region and one in the intron region. Variants in the 2 coding regions resulted in amino acid changes. The population had 3 genotypes of GG, AG, and AA, and individuals with the AA genotype had lower WBSF values (p < 0.05). The H3H3 haplotype combinations could improve meat tenderness by reducing the WBSF values and the cooking loss rate (CLR) (p < 0.05). H1H1 haplotype combinations were associated with the increased drip loss rate (DLR) (p < 0.05). The presence of the H1 haplotype was associated the increased CLR in yaks, while that of the H2 haplotype was associated with the decreased DLR in yaks (p < 0.05). These results demonstrated that the HSL gene may influence the meat quality traits in yaks by affecting the IMF content in muscle tissues. Consequently, the HSL gene can possibly be used as a biomarker for improving the meat quality traits in yaks in the future.
ESTHER : Wang_2023_Animals.(Basel)_13_
PubMedSearch : Wang_2023_Animals.(Basel)_13_
PubMedID: 38067071

Title : On the Binding Mode and Molecular Mechanism of Enzymatic Polyethylene Terephthalate Degradations - Falkenstein_2023_ACS.Catal_13_6919
Author(s) : Falkenstein P , Zhao Z , Di Pede-Mattatelli A , Kunze G , Sommer M , Sonnendecker C , Zimmermann W , Colizzi F , Matysik J , Song C
Ref : ACS Catal , 13 :6919 , 2023
Abstract : Enzymatic degradation of polyethylene terephthlate (PET) by polyester hydrolases is currently subject to intensive research, as it is considered as a potential eco-friendly recycling method for plastic waste. However, the substrate-binding mode and the molecular mechanism of enzymatic PET hydrolysis are still under intense investigation, and controversial hypotheses have been presented. To help unravel the inherent mechanism of biocatalytic PET degradation at the atomic level, we performed solid-state NMR measurements of a cutinase from Thermobifida fusca (TfCut2) embedded in trehalose glasses together with chemically synthesized, amorphous 13C(O)-labeled oligomeric PET. The resulting ternary enzyme-PET-trehalose glassy system enabled advanced solid-state NMR methods for real-time tracking of the enzymatic PET degradation and the investigation of PET chain dynamics. Combined with enhanced-sampling molecular dynamics simulations, specific enzymesubstrate interactions during the degradation process could also be monitored. Our results demonstrate that the PET chain is first cleaved by TfCut2 in blocks of at least one repeat unit and further to terephthalic acid and ethylene glycol. Moreover, the second step (formation of final hydrolysis products) appears to be rate-limiting in such reactions. The observed dynamic changes and interfacial protein contacts of 13C-labeled PET carbonyl groups suggest that only one PET repeat unit is bound to the enzyme during the degradation process while the rest of the PET chain is only loosely confined to the active site. These results, not accessible by using conventional solution enzyme samples and small nonhydrolyzable substrates, provide a better understanding of the biocatalytic PET degradation mechanism of polyester hydrolases.
ESTHER : Falkenstein_2023_ACS.Catal_13_6919
PubMedSearch : Falkenstein_2023_ACS.Catal_13_6919
Gene_locus related to this paper: thefu-q6a0i4

Title : Discovery of a new highly pathogenic toxin involved in insect sepsis - Zhang_2023_Microbiol.Spectr__e0142223
Author(s) : Zhang Y , Li H , Wang F , Liu C , Reddy GVP , Li Z , Sun Y , Zhao Z
Ref : Microbiol Spectr , :e0142223 , 2023
Abstract : Insect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode Steinernema feltiae and the entomopathogenic bacteria Xenorhabdus bovienii, which operate symbiotically, against the wax moth Galleria mellonella. Maximum mortality was observed at 25 degreesC while the optimal infestation efficiency was 20 nematodes per host. After infestation, G. mellonella displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The X. bovienii, released by S. feltiae, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host G. mellonella was usually killed within 24 h due to disseminated septicemia. Additionally, X. bovienii infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall, X. bovienii induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides. IMPORTANCE As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found Steinernema feltiae and Xenorhabdus bovienii were highly virulent against the insects. After infective juvenile injection, Galleria mellonella quickly turned black and softened with increasing esterase activity. Simultaneously, X. bovienii attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of X. bovienii, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.
ESTHER : Zhang_2023_Microbiol.Spectr__e0142223
PubMedSearch : Zhang_2023_Microbiol.Spectr__e0142223
PubMedID: 37787562

Title : Structure and function of the metagenomic plastic-degrading polyester hydrolase PHL7 bound to its product - Richter_2023_Nat.Commun_14_1905
Author(s) : Richter PK , Blazquez-Sanchez P , Zhao Z , Engelberger F , Wiebeler C , Kunze G , Frank R , Krinke D , Frezzotti E , Lihanova Y , Falkenstein P , Matysik J , Zimmermann W , Strater N , Sonnendecker C
Ref : Nat Commun , 14 :1905 , 2023
Abstract : The recently discovered metagenomic-derived polyester hydrolase PHL7 is able to efficiently degrade amorphous polyethylene terephthalate (PET) in post-consumer plastic waste. We present the cocrystal structure of this hydrolase with its hydrolysis product terephthalic acid and elucidate the influence of 17 single mutations on the PET-hydrolytic activity and thermal stability of PHL7. The substrate-binding mode of terephthalic acid is similar to that of the thermophilic polyester hydrolase LCC and deviates from the mesophilic IsPETase. The subsite I modifications L93F and Q95Y, derived from LCC, increased the thermal stability, while exchange of H185S, derived from IsPETase, reduced the stability of PHL7. The subsite II residue H130 is suggested to represent an adaptation for high thermal stability, whereas L210 emerged as the main contributor to the observed high PET-hydrolytic activity. Variant L210T showed significantly higher activity, achieving a degradation rate of 20 microm h(-1) with amorphous PET films.
ESTHER : Richter_2023_Nat.Commun_14_1905
PubMedSearch : Richter_2023_Nat.Commun_14_1905
PubMedID: 37019924
Gene_locus related to this paper: 9firm-PHL7

Title : Whole-genome analysis of Comamonas sp. USTBZA1 for biodegrading diethyl phthalate - Zhao_2023_3.Biotech_13_329
Author(s) : Zhao Z , Liu Y , Liu C , Xu Q , Song M , Yan H
Ref : 3 Biotech , 13 :329 , 2023
Abstract : Extensive use of phthalic acid esters (PAEs) as plasticizer causes diffusion into the environment, which posed a great threat to mankind. It was reported that Comamonas sp. was a potentially robust aromatic biodegrader. Although the biodegradation of several PAEs by Comamonas sp. was studies, the comprehensive genomic analysis of Comamonas sp. was few reported. In the present study, one promising bacterial strain for biodegrading diethyl phthalate (DEP) was successfully isolated from activated sludge and characterized as Comamonas sp. USTBZA1 based on the 16S rRNA sequence analysis. The results showed that pH 7.5, 30 degreesC and inoculum volume ratio of 6% were optimal for biodegradation. Initial DEP of 50 mg/L could be completely biodegrade by strain USTBZA1 within 24 h which conformed to the Gompertz model. Based on the Q-TOF LC/MS analysis, monoethyl phthalate (MEP) and phthalic acid (PA) were identified as the metabolic products of DEP biodegradation by USTBZA1. Furthermore, the whole genome of Comamonas sp. USTBZA1 was analyzed to clarify the molecular mechanism for PAEs biodegradation by USTBZA1. There were 3 and 41 genes encoding esterase/arylesterase and hydrolase, respectively, and two genes regions (pht34512 and pht4253) were responsible for the conversion of PA to protocatechuate (PCA), and two genes regions (ligCBAIKJ) were involved in PCA metabolism in USTBZA1. These results substantiated that Comamonas sp. USTBZA1 has potential application in the DEP bioremediation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03736-3.
ESTHER : Zhao_2023_3.Biotech_13_329
PubMedSearch : Zhao_2023_3.Biotech_13_329
PubMedID: 37670801

Title : Parkinson's disease and comorbid myasthenia gravis: a case report and literature review - Zhang_2023_Front.Neurol_14_1303434
Author(s) : Zhang Q , Xu E , Li HF , Chan P , Zhao Z , Ma J
Ref : Front Neurol , 14 :1303434 , 2023
Abstract : BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Myasthenia gravis (MG) is a rare autoimmune disease caused by antibodies against the neuromuscular junction. PD and comorbid MG are rarely seen. CASE PRESENTATION: Here we report on a patient who was diagnosed with PD and MG. A 74-year-old man had a 4-year history of bradykinesia and was diagnosed with PD. He subsequently developed incomplete palpebral ptosis, apparent dropped head, and shuffling of gait. The results of neostigmine tests were positive. Repetitive nerve stimulation (RNS) showed significant decremental responses at 3 and 5 Hz in the orbicularis oculi. The patient's anti-acetylcholine receptor (anti-AchR) antibody serum level was also elevated. Meanwhile, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine positron emission tomography-computed tomography ((18)F-AV133 PET-CT) scan revealed a significant decrease in uptake in the bilateral putamen. After addition of cholinesterase inhibitors, his symptoms of palpebral ptosis and head drop improved greatly and he showed a good response to levodopa. CONCLUSION: Although PD with MG is rare, we still need to notice the possibility that a PD patient may have comorbid MG. The underlying mechanism of PD and comorbid MG remains unknown, but an imbalance between the neurotransmitters dopamine and acetylcholine and the immune system are likely to play significant roles in the pathogenesis. In this article, we present our case and a literature review on the co-occurrence of PD and MG, reviewing their clinical features, and discuss the underlying pathogenic mechanism of this comorbidity.
ESTHER : Zhang_2023_Front.Neurol_14_1303434
PubMedSearch : Zhang_2023_Front.Neurol_14_1303434
PubMedID: 38259657

Title : Green-Efficient Enzymatic Synthesis and Characterization of Liposoluble 6'\/6-O-Lauryl Phenolic Glycosides with Enhanced Intestinal Permeability - Xu_2023_J.Agric.Food.Chem__
Author(s) : Xu Z , Liu S , Lai H , You L , Zhao Z
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Arbutin, salidroside, polydatin, and phlorizin are typically natural bioactive phenolic glycosides. To improve the liposolubility and bioavailability, highly liposoluble derivatives including 6'-O-lauryl arbutin, 6'-O-lauryl salidroside, 6''-O-lauryl polydatin, and 6''-O-lauryl phlorizin were efficiently synthesized by enzymatic acylation in a green solvent 2-MeTHF. Their reaction conversions reached 84.4, 99.5, 99.8, and 89.1%, respectively, when catalyzed by Lipozyme 435 at 20 mg/mL at 50 degreesC. As expected, the derivatives had high log P (1.66-2.37) and retained good antioxidant activity, making them potential alternatives to butylated hydroxytoluene (BHT) and tert-butyl-hydroquinone (TBHQ) in lipid systems. Then, the intestinal permeability characteristics and metabolism of phenolic glycosides and their derivatives were investigated based on Caco-2 monolayers. The permeability of polydatin and phlorizin was mainly through active transport, but that of arbutin and salidroside involved both passive diffusion and active uptake. The acylated derivatives suffered from severe CES-mediated hydrolysis but exhibited a larger transported amount than phenolic glycosides.
ESTHER : Xu_2023_J.Agric.Food.Chem__
PubMedSearch : Xu_2023_J.Agric.Food.Chem__
PubMedID: 37167604

Title : Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters - Li_2023_Foods_12_1977
Author(s) : Li D , Guo J , Ma H , Pei L , Liu X , Wang H , Chen R , Zhao Z , Gao H
Ref : Foods , 12 :1977 , 2023
Abstract : Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor.
ESTHER : Li_2023_Foods_12_1977
PubMedSearch : Li_2023_Foods_12_1977
PubMedID: 37238795

Title : Microbiome dynamics during anaerobic digestion of food waste and the genetic potential for poly (lactic acid) co-digestion - Zhu_2023_Chem.Eng.J__145194
Author(s) : Zhu X , Zhu S , Zhao Z , Kang X , Ju F
Ref : Chemical Engineering Journal , :145194 , 2023
Abstract : Anaerobic digestion of food waste (FW) and potential co-digestion with biodegradable packaging material (i.e., bioplastics) have been promising resource recovery strategies. Unveiling the microbiome dynamics involved in the digestion process and exploring the genetic potential for poly (lactic acid) hydrolysis therein provide the fundamental basis for further process control and optimization. The current study has shown that the FW-digesting microbiome changed in both composition and activity-dormancy status while consuming available substrates. The microbiome assembly was mainly driven by homogeneous selection (36.7% on average) and drift (59.5% on average), and the homogeneous selection effect scaled with the availability of substrates. Based on the ratio between the relative activity and abundance, the microbiome was clustered into four groups. The Group (1) microbes, including Bacterioidetes_vadinHA17 and Syntrophomonadaceae, accumulated high relative abundance during the early stage of the digestion process but entered dormancy after the preferred substrate was consumed. Other members, i.e., the Group 4 Syntrophobacteraceae and Pseudomonadaceae, showed low abundance but disproportional activity during the later stage of the digestion process. The genome-centric metagenomics revealed that inherent AD microbes, especially the Group (1) microbes, harbored robust hydrolase genes, facilitating the PLA degradation. In fact, PLA addition to FW digestor led to significant methane production enhancement (14%) but negligible changes in microbiome composition. The outcome of this study provided the theoretical basis for developing microbiome management and engineering strategies that prospect efficient FW and PLA co-digestion processes.
ESTHER : Zhu_2023_Chem.Eng.J__145194
PubMedSearch : Zhu_2023_Chem.Eng.J__145194

Title : Hydrolysis-Resistant Ester-Based Linkers for Development of Activity-Based NIR Bioluminescence Probes - Yadav_2023_J.Am.Chem.Soc__
Author(s) : Yadav AK , Zhao Z , Weng Y , Gardner SH , Brady CJ , Pichardo Peguero OD , Chan J
Ref : Journal of the American Chemical Society , : , 2023
Abstract : Activity-based sensing (ABS) probes equipped with a NIR bioluminescence readout are promising chemical tools to study cancer biomarkers owing to their high sensitivity and deep tissue compatibility. Despite the demand, there is a dearth of such probes because NIR substrates (e.g., BL660 (a NIR luciferin analog)) are not equipped with an appropriate attachment site for ABS trigger installation. For instance, our attempts to mask the carboxylic acid moiety with standard self-immolative benzyl linkers resulted in significant background signals owing to undesirable ester hydrolysis. In this study, we overcame this longstanding challenge by rationally designing a new hydrolysis-resistant ester-based linker featuring an isopropyl shielding arm. Compared to the parent, the new design is 140.5-fold and 67.8-fold more resistant toward spontaneous and esterase-mediated hydrolysis, respectively. Likewise, we observed minimal cleavage of the ester moiety when incubated with a panel of enzymes possessing ester-hydrolyzing activity. These impressive in vitro results were corroborated through a series of key experiments in live cells. Further, we showcased the utility of this technology by developing the first NIR bioluminescent probe for nitroreductase (NTR) activity and applied it to visualize elevated NTR expression in oxygen deficient lung cancer cells and in a murine model of non-small cell lung cancer. The ability to monitor the activity of this key biomarker in a deep tissue context is critical because it is associated with tumor hypoxia, which in turn is linked to drug resistance and aggressive cancer phenotypes.
ESTHER : Yadav_2023_J.Am.Chem.Soc__
PubMedSearch : Yadav_2023_J.Am.Chem.Soc__
PubMedID: 36603103

Title : Synergism of Feeding and Digestion Regulated by the Neuropeptide F System in Ostrinia furnacalis Larvae - Zhao_2023_Cells_12_
Author(s) : Zhao J , Song Y , Jiang X , He L , Wei L , Zhao Z
Ref : Cells , 12 : , 2023
Abstract : Feeding is crucial for the growth and survival of animals, including humans, but relatively little is known about how it is regulated. Here, we show that larval feeding in Ostrinia furnacalis is regulated by neuropeptide F (NPF, the homologous peptide of mammalian NPY) via the insulin signalling pathway in the midgut. Furthermore, the genes pi3k and mtor in the insulin pathway positively regulate alpha-amylase and lipase of the midgut by recruiting the transcription factors c-Myc and PPARgamma for binding to the promotors of these two enzymes. Importantly, we find that the feeding behaviour and the digestive system of midgut in O. furnacalis larvae are closely related and interactive in that knocking down alpha-amylase or lipase induces a reduction in larval feeding, while food-deprived larvae lead to fewer expressions of alpha-amylase and lipase. Importantly, it is the gut NPF that regulates the alpha-amylase and lipase, while variations of alpha-amylase and lipase may feed back to the brain NPF. This current study reveals a molecular feedback mechanism between feeding behaviour and the digestive system that is regulated by the conserved NPF via insulin signalling systems in the midgut of O. furnacalis larvae.
ESTHER : Zhao_2023_Cells_12_
PubMedSearch : Zhao_2023_Cells_12_
PubMedID: 36611986

Title : The Patatin-Like Phospholipase Domain Containing Protein 7 Regulates Macrophage Classical Activation through SIRT1\/NF-B and p38 MAPK Pathways - Zhao_2022_Int.J.Mol.Sci_23_
Author(s) : Zhao Z , Heier C , Pang H , Wang Y , Huang F , Chang P
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Lysophosphatidylcholine (LPC) is a bioactive lipid that modulates macrophage polarization during immune responses, inflammation, and tissue remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) is a lysophospholipase with a preference for LPC. However, the role of PNPLA7 in macrophage polarization as an LPC hydrolase has not been explored. In the current study, we found that PNPLA7 is highly expressed in naive macrophages and downregulated upon lipopolysaccharide (LPS)-induced polarization towards the classically activated (M1) phenotype. Consistently, overexpression of PNPLA7 suppressed the expression of proinflammatory M1 marker genes, including interleukin 1beta (IL-1beta), IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TNF-alpha), whereas knockdown of PNPLA7 augmented the inflammatory gene expression in LPS-challenged macrophages. PNPLA7 overexpression and knockdown increased and decreased Sirtuin1 (SIRT1) mRNA and protein levels, respectively, and affected the acetylation of the nuclear factor-kappa B (NF-kappaB) p65 subunit, a key transcription factor in M1 polarization. In addition, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK) were suppressed and enhanced by PNPLA7 overexpression and knockdown, respectively. Taken together, these findings suggest that PNPLA7 suppresses M1 polarization of LPS-challenged macrophages by modulating SIRT1/NF-kappaB- and p38 MAPK-dependent pathways.
ESTHER : Zhao_2022_Int.J.Mol.Sci_23_
PubMedSearch : Zhao_2022_Int.J.Mol.Sci_23_
PubMedID: 36499308

Title : Low Carbon Footprint Recycling of Post-Consumer PET Plastic with a Metagenomic Polyester Hydrolase - Sonnendecker_2022_ChemSusChem_15_e202101062
Author(s) : Sonnendecker C , Oeser J , Richter PK , Hille P , Zhao Z , Fischer C , Lippold H , Blazquez-Sanchez P , Engelberger F , Ramirez-Sarmiento CA , Oeser T , Lihanova Y , Frank R , Jahnke HG , Billig S , Abel B , Strater N , Matysik J , Zimmermann W
Ref : ChemSusChem , 15 :e202101062 , 2022
Abstract : Our planet is flooded with plastics and the need for sustainable recycling strategies of polymers has become increasingly urgent. Enzyme-based hydrolysis of post-consumer plastic is an emerging strategy for closed-loop recycling of polyethylene terephthalate (PET). The polyester hydrolase PHL7 isolated from a compost metagenome completely hydrolyzed amorphous PET films, releasing 91 mg of terephthalic acid per hour and mg of enzyme. Degradation rates of the PET film of 6.8 microm h -1 were monitored by vertical scanning interferometry. Structural analysis indicated the importance of leucine at position 210 for the extraordinarily high PET-hydrolyzing activity of PHL7. Within 24 h, 0.6 mg enzyme g PET -1 completely degraded post-consumer thermoform PET packaging in an aqueous buffer at 70 degreesC without any energy-intensive pretreatments. Terephthalic acid recovered from the enzymatic hydrolysate was used to synthesize virgin PET, demonstrating the potential of polyester hydrolases as catalysts in sustainable PET recycling processes with a low carbon footprint.
ESTHER : Sonnendecker_2022_ChemSusChem_15_e202101062
PubMedSearch : Sonnendecker_2022_ChemSusChem_15_e202101062
PubMedID: 34129279
Gene_locus related to this paper: 9firm-PHL7

Title : Structural Basis for the Regiospecificity of a Lipase from Streptomyces sp. W007 - Zhao_2022_Int.J.Mol.Sci_23_5822
Author(s) : Zhao Z , Chen S , Xu L , Cai J , Wang J , Wang Y
Ref : Int J Mol Sci , 23 :5822 , 2022
Abstract : The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a alpha-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases.
ESTHER : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedSearch : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedID: 35628632
Gene_locus related to this paper: 9actn-h0b8d4

Title : Adipose tissue-specific ablation of Ces1d causes metabolic dysregulation in mice - Li_2022_Life.Sci.Alliance_5_
Author(s) : Li G , Li X , Yang L , Wang S , Dai Y , Fekry B , Veillon L , Tan L , Berdeaux R , Eckel-Mahan K , Lorenzi PL , Zhao Z , Lehner R , Sun K
Ref : Life Sciences Alliance , 5 : , 2022
Abstract : Carboxylesterase 1d (Ces1d) is a crucial enzyme with a wide range of activities in multiple tissues. It has been reported to localize predominantly in ER. Here, we found that Ces1d levels are significantly increased in obese patients with type 2 diabetes. Intriguingly, a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce a unique set of fatty acids. We further revealed that adipose tissue-specific Ces1d knock-out (FKO) mice gained more body weight with increased fat mass during a high fat-diet challenge. The FKO mice exhibited impaired glucose and lipid metabolism and developed exacerbated liver steatosis. Mechanistically, deficiency of Ces1d induced abnormally large lipid droplet deposition in the adipocytes, causing ectopic accumulation of triglycerides in other peripheral tissues. Furthermore, loss of Ces1d diminished the circulating free fatty acids serving as signaling molecules to trigger the epigenetic regulations of energy metabolism via lipid-sensing transcriptional factors, such as HNF4alpha. The metabolic disorders induced an unhealthy microenvironment in the metabolically active tissues, ultimately leading to systemic insulin resistance.
ESTHER : Li_2022_Life.Sci.Alliance_5_
PubMedSearch : Li_2022_Life.Sci.Alliance_5_
PubMedID: 35459739
Gene_locus related to this paper: mouse-Ces1d

Title : Strigolactone is involved in nitric oxide-enhanced the salt resistance in tomato seedlings - Liu_2022_J.Plant.Res__
Author(s) : Liu H , Li C , Yan M , Zhao Z , Huang P , Wei L , Wu X , Wang C , Liao W
Ref : J Plant Res , : , 2022
Abstract : Both strigolactones (SLs) and nitric oxide (NO) are regulatory signals with diverse roles during stress responses. At present, the interaction and mechanism of SLs and NO in tomato salt tolerance remain unclear. In the current study, tomato 'Micro-Tom' was used to study the roles and interactions of SLs and NO in salinity stress tolerance. The results show that 15 microM SLs synthetic analogs GR24 and 10 microM NO donor S-nitrosoglutathione (GSNO) promoted seedling growth under salt stress. TIS108 (an inhibitor of strigolactone synthesis) suppressed the positive roles of NO in tomato growth under salt stress, indicating that endogenous SLs might be involved in NO-induced salt response in tomato seedlings. Meanwhile, under salt stress, GSNO or GR24 treatment induced the increase of endogenous SLs content in tomato seedlings. Moreover, GR24 or GSNO treatment effectively increased the content of chlorophyll, carotenoids and ascorbic acid (ASA), and enhanced the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), glutathione reductase (GR) and cleavage dioxygenase (CCD) enzyme. Additionally, GSNO or GR24 treatment also up-regulated the expression of SLs synthesis genes (SlCCD7, SlCCD8, SlD27 and SlMAX1) and its signal transduction genes (SlD14 and SlMAX2) in tomato seedlings under salt stress. While, a strigolactone synthesis inhibitor TIS108 blocked the increase of endogenous SLs, chlorophyll, carotenoids and ASA content, and antioxidant enzyme, GR, CCD enzyme activity and SLs-related gene expression levels induced by GSNO. Thus, SLs may play an important role in NO-enhanced salinity tolerance in tomato seedlings by increasing photosynthetic pigment content, enhancing antioxidant capacity and improving endogenous SLs synthesis.
ESTHER : Liu_2022_J.Plant.Res__
PubMedSearch : Liu_2022_J.Plant.Res__
PubMedID: 35106650

Title : Human umbilical cord mesenchymal stem cells-derived exosomes for treating traumatic pancreatitis in rats - Han_2022_Stem.Cell.Res.Ther_13_221
Author(s) : Han L , Zhao Z , Chen X , Yang K , Tan Z , Huang Z , Zhou L , Dai R
Ref : Stem Cell Res Ther , 13 :221 , 2022
Abstract : BACKGROUND: The therapeutic and protective effects of human umbilical cord mesenchymal stem cells-exosomes (hucMSC-Exs) on traumatic pancreatitis (TP) remain unknown. Here, we established a rat model of TP and evaluated and compared the therapeutic effects of hUC-MSCs and hucMSC-Exs. METHODS: HucMSC-Exs were obtained by ultracentrifugation and identified using transmission electron microscopy and western blot analysis. TP rats were treated by tail vein injection of hUC-MSCs and hucMSC-Exs. Their homing in rats was observed by performing fluorescence microscopy. The degree of pancreatic tissue damage was assessed by HE staining, the expression levels of amylase, lipase, and inflammatory cytokines were detected by ELISA, apoptosis was detected by TUNEL assay, and the expression levels of various apoptosis-related proteins were detected by western-blot. The expression levels of apoptosis-related molecular markers were detected by RT-qPCR. RESULTS: The colonization of exosomes was observed in pancreatic tissue. Compared to TP group, the histopathological score of pancreas was significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). Compared to TP group, the activity of serum amylase and lipase was significantly decreased (P < 0.05). The expression levels of IL-6 and TNF-alpha were significantly decreased, while those of IL-10 and TGF-beta were significantly increased (P < 0.05). The apoptosis index of the TP group was significantly increased (P < 0.05), whereas that of the TP + hUC-MSCs and TP + hucMSC-Exs groups was significantly decreased (P < 0.05). Compared to TP group, the expression levels of Bax, Bcl-2, and Caspase-3 were significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). CONCLUSION: HucMSC-Exs can colonize injured pancreatic tissue, inhibit the apoptosis of acinar cells, and control the systemic inflammatory response to facilitate the repair of pancreatic tissue.
ESTHER : Han_2022_Stem.Cell.Res.Ther_13_221
PubMedSearch : Han_2022_Stem.Cell.Res.Ther_13_221
PubMedID: 35619158

Title : Activity-based Photoacoustic Probes Reveal Elevated Intestinal MGL and FAAH Activity in a Murine Model of Obesity - Lucero_2022_Angew.Chem.Int.Ed.Engl__
Author(s) : Lucero MY , Gardner SH , Yadav AK , Borri A , Zhao Z , Chan J
Ref : Angew Chem Int Ed Engl , : , 2022
Abstract : Obesity is a chronic health condition characterized by the accumulation of excessive body fat which can lead to and exacerbate cardiovascular disease, type-II diabetes, high blood pressure, and cancer through systemic inflammation. Unfortunately, visualizing key mediators of the inflammatory response such as monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) in a selective manner is a profound challenge owing to an overlapping substrate scope that involves arachidonic acid (AA). Specifically, these enzymes work in concert to generate AA, which in the context of obesity, has been implicated to control appetite and energy metabolism. In this study, we developed the first selective activity-based sensing probes to detect MGL (PA-HD-MGL) and FAAH (PA-HD-FAAH) activity via photoacoustic imaging. Activation of PA-HD-MGL and PA-HD-FAAH by their target enzymes is 1.88-fold and 1.50-fold higher, respectively. Due to their exceptional selectivity profiles and deep-tissue photoacoustic imaging capabilities, these probes were employed to measure MGL and FAAH activity in a murine model of obesity. Contrary to reports suggesting levels of MGL should be attenuated, our results revealed a marked increase of both targets in the gastrointestinal tract. These key finding sets the stage to uncover the role of the endocannabinoid pathway in obesity-mediated inflammation.
ESTHER : Lucero_2022_Angew.Chem.Int.Ed.Engl__
PubMedSearch : Lucero_2022_Angew.Chem.Int.Ed.Engl__
PubMedID: 36083191

Title : MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR - Wang_2022_Front.Vet.Sci_9_948873
Author(s) : Wang J , Hao Z , Hu L , Qiao L , Luo Y , Hu J , Liu X , Li S , Zhao F , Shen J , Li M , Zhao Z
Ref : Front Vet Sci , 9 :948873 , 2022
Abstract : In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep.
ESTHER : Wang_2022_Front.Vet.Sci_9_948873
PubMedSearch : Wang_2022_Front.Vet.Sci_9_948873
PubMedID: 35990270

Title : Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA - Liu_2022_Plant.Cell_34_3301
Author(s) : Liu T , Zhang X , Zhang H , Cheng Z , Liu J , Zhou C , Luo S , Luo W , Li S , Xing X , Chang Y , Shi C , Ren Y , Zhu S , Lei C , Guo X , Wang J , Zhao Z , Wang H , Zhai H , Lin Q , Wan J
Ref : Plant Cell , 34 :3301 , 2022
Abstract : Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
ESTHER : Liu_2022_Plant.Cell_34_3301
PubMedSearch : Liu_2022_Plant.Cell_34_3301
PubMedID: 35670739

Title : Monoacylglycerol lipase from marine Geobacillus sp. showing lysophospholipase activity and its application in efficient soybean oil degumming - Liu_2022_Food.Chem_406_134506
Author(s) : Liu X , Wang W , Zhao Z , Xu L , Yang B , Lan D , Wang Y
Ref : Food Chem , 406 :134506 , 2022
Abstract : Enzymatic degumming is an essential refining process to improve oil quality. In this study, a monoacylglycerol lipase GMGL was derived from marine Geobacillus sp., and was found that not only took monoacylglycerol (MAG) as substrate, but also had activity toward lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and glycerolphosphatidylcholine (GPC). Binding free energy showed LPC and LPE could bind with enzyme stably as MAG. It presented great potential in the field of enzymatic degumming. The phosphorus content in crude soybean oil decreased from 680.50 to 2.01 mg/kg and the yield of oil reached to 98.80 % after treating with phospholipase A1 (Lecitase Ultra) combined with lipase GMGL. An ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was developed to identify 21 differential phospholipids between crude soybean oil and enzymatic treatment. This work might shed some light on understanding the catalytic mechanism of monoacylglycerol lipase and provide an effective strategy for enzymatic degumming.
ESTHER : Liu_2022_Food.Chem_406_134506
PubMedSearch : Liu_2022_Food.Chem_406_134506
PubMedID: 36463594

Title : Single-Nucleotide Polymorphisms Promote Dysregulation Activation by Essential Gene Mediated Bio-Molecular Interaction in Breast Cancer - Wang_2021_Front.Oncol_11_791943
Author(s) : Wang X , Zhao Z , Han X , Zhang Y , Li F , Li H
Ref : Front Oncol , 11 :791943 , 2021
Abstract : BACKGROUND: Breast cancer (BRCA) is a malignant tumor with a high mortality rate and poor prognosis in patients. However, understanding the molecular mechanism of breast cancer is still a challenge. MATERIALS AND METHODS: In this study, we constructed co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene-expression profiles and clinical data were integrated to detect breast cancer survival modules and the leading genes related to prognostic risk. Finally, we introduced machine learning algorithms to build a predictive model aiming to discover potential key biomarkers. RESULTS: A total of 42 prognostic modules for breast cancer were identified. The nomogram analysis showed that 42 modules had good risk assessment performance. Compared to clinical characteristics, the risk values carried by genes in these modules could be used to classify the high-risk and low-risk groups of patients. Further, we found that 16 genes with significant differential expressions and obvious bridging effects might be considered biological markers related to breast cancer. Single-nucleotide polymorphisms on the CYP24A1 transcript induced RNA structural heterogeneity, which affects the molecular regulation of BRCA. In addition, we found for the first time that ABHD11-AS1 was significantly highly expressed in breast cancer. CONCLUSION: We integrated clinical prognosis information, RNA sequencing data, and drug targets to construct a breast cancer-related risk module. Through bridging effect measurement and machine learning modeling, we evaluated the risk values of the genes in the modules and identified potential biomarkers for breast cancer. The protocol provides new insight into deciphering the molecular mechanism and theoretical basis of BRCA.
ESTHER : Wang_2021_Front.Oncol_11_791943
PubMedSearch : Wang_2021_Front.Oncol_11_791943
PubMedID: 34926308
Gene_locus related to this paper: human-ABHD11

Title : Case Study Using Recommended Reference Genes Actin and 18S for Reverse-Transcription Quantitative Real-Time PCR Analysis in Myzus persicae - Rahman_2021_PLoS.One_16_e0258201
Author(s) : Rahman S , Zhao Z , Umair Sial M , Zhang Y , Jiang H
Ref : PLoS ONE , 16 :e0258201 , 2021
Abstract : Myzus persicae is a globally important pest with the ability to adjust to a wide range of environmental situations, and many molecular technologies have been developed and applied to understand the biology and/or control this pest insect directly. Reverse-transcription quantitative real-time PCR (RT-qPCR) is a primary molecular technology that is used to quantify gene expression. Choosing a stable reference gene is significantly important for precisely clarifying the expression level of the target gene. Actin and 18S have been recommended as stable compounds for real-time RT-qPCR in M. persicae under the tested biotic and abiotic conditions. In this study, we checked the stability of Actin and 18S by analyzing the relative expression levels of the cytochrome 450 monooxygenase family member genes CYP6CY3 and CYP6-1, carboxylesterase gene E4 and vacuolar protein sorting gene VPS11 via RT-qPCR under various conditions. The expression levels of these four target genes were normalized using both Actin and 18S individually and the combination of these two genes. Our results confirmed that Actin and 18S can be used as reference genes to normalize the expression of target genes under insecticide treatment and starvation in M. persicae. However, at the developmental stages of M. persicae, the expression of the four tested target genes was normalized stably by Actin but not 18S, with the latter presenting a problematic change with the developmental stages. Thus, the stability of reference genes in response to diverse biotic and abiotic factors should be evaluated before each RT-qPCR experiment.
ESTHER : Rahman_2021_PLoS.One_16_e0258201
PubMedSearch : Rahman_2021_PLoS.One_16_e0258201
PubMedID: 34669698

Title : Chemoproteomics-Enabled De Novo Discovery of Photoswitchable Carboxylesterase Inhibitors for Optically Controlled Drug Metabolism - Dwyer_2021_Angew.Chem.Int.Ed.Engl_60_3071
Author(s) : Dwyer BG , Wang C , Abegg D , Racioppo B , Qiu N , Zhao Z , Pechalrieu D , Shuster A , Hoch DG , Adibekian A
Ref : Angew Chem Int Ed Engl , 60 :3071 , 2021
Abstract : Herein, we report arylazopyrazole ureas and sulfones as a novel class of photoswitchable serine hydrolase inhibitors and present a chemoproteomic platform for rapid discovery of optically controlled serine hydrolase targets in complex proteomes. Specifically, we identify highly potent and selective photoswitchable inhibitors of the drug-metabolizing enzymes carboxylesterases 1 and 2 and demonstrate their pharmacological application by optically controlling the metabolism of the immunosuppressant drug mycophenolate mofetil. Collectively, this proof-of-concept study provides a first example of photopharmacological tools to optically control drug metabolism by modulating the activity of a metabolizing enzyme. Our arylazopyrazole ureas and sulfones offer synthetically accessible scaffolds that can be expanded to identify specific photoswitchable inhibitors for other serine hydrolases, including lipases, peptidases, and proteases. Our chemoproteomic platform can be applied to other photoswitches and scaffolds to achieve optical control over diverse protein classes.
ESTHER : Dwyer_2021_Angew.Chem.Int.Ed.Engl_60_3071
PubMedSearch : Dwyer_2021_Angew.Chem.Int.Ed.Engl_60_3071
PubMedID: 33035395

Title : Glycerol is Released from a New Path in MGL Lipase Catalytic Process - Lan_2021_J.Chem.Inf.Model__
Author(s) : Lan D , Li S , Tang W , Zhao Z , Luo M , Yuan S , Xu J , Wang Y
Ref : J Chem Inf Model , : , 2021
Abstract : Traditionally, it is believed that the substrate and products of a monoacylglycerol lipase (MGL) share the same path to enter and exit the catalytic site. Glycerol (a product of MGL), however, was recently hypothesized to be released through a different path. In order to improve the catalytic efficacy and thermo-stability of MGL, it is important to articulate the pathways of a MGL products releasing. In this study, with structure biological approaches, biochemical experiments, and in silico methods, we prove that glycerol is released from a different path in the catalytic site indeed. The fatty acid (another product of MGL) does share the same binding path with the substrate. This discovery paves a new road to design MGL inhibitors or optimize MGL catalytic efficacy.
ESTHER : Lan_2021_J.Chem.Inf.Model__
PubMedSearch : Lan_2021_J.Chem.Inf.Model__
PubMedID: 34873908

Title : Characterization and genomic analysis of an efficient dibutyl phthalate degrading bacterium Microbacterium sp. USTB-Y - Zhao_2021_World.J.Microbiol.Biotechnol_37_212
Author(s) : Zhao Z , Liu C , Xu Q , Ahmad S , Zhang H , Pang Y , Aikemu A , Liu Y , Yan H
Ref : World J Microbiol Biotechnol , 37 :212 , 2021
Abstract : A promising bacterial strain for biodegrading dibutyl phthalate (DBP) was successfully isolated from activated sludge and characterized as a potential novel Microbacterium sp. USTB-Y based on 16S rRNA sequence analysis and whole genome average nucleotide identity (ANI). Initial DBP of 50 mg/L could be completely biodegraded by USTB-Y both in mineral salt medium and in DBP artificially contaminated soil within 12 h at the optimal culture conditions of pH 7.5 and 30 degC, which indicates that USTB-Y has a strong ability in DBP biodegradation. Phthalic acid (PA) was identified as the end-product of DBP biodegraded by USTB-Y using GC/MS. The draft genome of USTB-Y was sequenced by Illumina NovaSeq and 29 and 188 genes encoding for putative esterase/carboxylesterase and hydrolase/alpha/beta hydrolase were annotated based on NR (non redundant protein sequence database) analysis, respectively. Gene3781 and gene3780 from strain USTB-Y showed 100% identity with dpeH and mpeH from Microbacterium sp. PAE-1. But no phthalate catabolic gene (pht) cluster was found in the genome of strain USTB-Y. The results in the present study are valuable for obtaining a more holistic understanding on diverse genetic mechanisms of PAEs biodegrading Microbacterium sp. strains.
ESTHER : Zhao_2021_World.J.Microbiol.Biotechnol_37_212
PubMedSearch : Zhao_2021_World.J.Microbiol.Biotechnol_37_212
PubMedID: 34738191
Gene_locus related to this paper: 9mico-DpeH , 9mico-MpeH

Title : Carboxylesterases from bacterial enrichment culture degrade strobilurin fungicides - Wang_2021_Sci.Total.Environ__152751
Author(s) : Wang W , Zhao Z , Yan H , Zhang H , Li QX , Liu X
Ref : Sci Total Environ , :152751 , 2021
Abstract : Strobilurin fungicides are a class of persistent fungicides frequently detected in the environment. Microbes can effectively degrade strobilurins, but the mechanisms are complex and diverse. Compared with isolated strains, bacterial consortia are more robust in terms of the degradation of multiple pollutants. The enrichment culture XS19 is a group of bacterial strains enriched from soil and degrades six strobilurins at 50 mg/L within 8 d, including azoxystrobin, picoxystrobin, trifloxystrobin, kresoxim-methyl, pyraclostrobin and enestroburin. LC-Q-TOF-MS analysis confirmed that XS19 can demethylate these strobilurins via hydrolysis of the methyl ester group. Analysis of the bacterial communities suggested that Pseudomonas (69.8%), Sphingobacterium (21.2%), Delftia (6.3%), and Achromobacter (1.6%) spp. were highly associated with the removal of strobilurins in the system. Metagenomics-based comprehensive analysis of XS19 suggested that carboxylesterases in Pseudomonas and Sphingobacterium play a central role in the catabolism of strobilurins. Moreover, the carboxylesterase inhibitor bis-p-nitrophenyl phosphate inhibited the degradation activity of strobilurins in XS19. This work proved that XS19 or carboxylesterases can effectively hydrolyze strobilurins, providing a reliable bioremediation paradigm.
ESTHER : Wang_2021_Sci.Total.Environ__152751
PubMedSearch : Wang_2021_Sci.Total.Environ__152751
PubMedID: 34979227

Title : COX-2\/sEH Dual Inhibitor PTUPB Alleviates CCl (4) -Induced Liver Fibrosis and Portal Hypertension - Zhao_2021_Front.Med.(Lausanne)_8_761517
Author(s) : Zhao Z , Zhang C , Lin J , Zheng L , Li H , Qi X , Huo H , Lou X , Hammock BD , Hwang SH , Bao Y , Luo M
Ref : Front Med (Lausanne) , 8 :761517 , 2021
Abstract : Background: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl) -benzenesulfonamide (PTUPB), a dual cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) inhibitor, was found to alleviate renal, pulmonary fibrosis and liver injury. However, few is known about the effect of PTUPB on liver cirrhosis. In this study, we aimed to explore the role of PTUPB in liver cirrhosis and portal hypertension (PHT). Method: Rat liver cirrhosis model was established via subcutaneous injection of carbon tetrachloride (CCl(4)) for 16 weeks. The experimental group received oral administration of PTUPB (10 mg/kg) for 4 weeks. We subsequently analyzed portal pressure (PP), liver fibrosis, inflammation, angiogenesis, and intra- or extrahepatic vascular remodeling. Additionally, network pharmacology was used to investigate the possible mechanisms of PTUPB in live fibrosis. Results: CCl(4) exposure induced liver fibrosis, inflammation, angiogenesis, vascular remodeling and PHT, and PTUPB alleviated these changes. PTUPB decreased PP from 17.50 +/- 4.65 to 6.37 +/- 1.40 mmHg, reduced collagen deposition and profibrotic factor. PTUPB alleviated the inflammation and bile duct proliferation, as indicated by decrease in serum interleukin-6 (IL-6), liver cytokeratin 19 (CK-19), transaminase, and macrophage infiltration. PTUPB also restored vessel wall thickness of superior mesenteric arteries (SMA) and inhibited intra- or extrahepatic angiogenesis and vascular remodeling via vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), etc. Moreover, PTUPB induced sinusoidal vasodilation by upregulating endothelial nitric oxide synthase (eNOS) and GTP-cyclohydrolase 1 (GCH1). In enrichment analysis, PTUPB engaged in multiple biological functions related to cirrhosis, including blood pressure, tissue remodeling, immunological inflammation, macrophage activation, and fibroblast proliferation. Additionally, PTUPB suppressed hepatic expression of sEH, COX-2, and transforming growth factor-beta (TGF-beta). Conclusion: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl)- benzenesulfonamide ameliorated liver fibrosis and PHT by inhibiting fibrotic deposition, inflammation, angiogenesis, sinusoidal, and SMA remodeling. The molecular mechanism may be mediated via the downregulation of the sEH/COX-2/TGF-beta.
ESTHER : Zhao_2021_Front.Med.(Lausanne)_8_761517
PubMedSearch : Zhao_2021_Front.Med.(Lausanne)_8_761517
PubMedID: 35004731

Title : Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats - Sun_2020_J.Int.Med.Res_48_300060520936177
Author(s) : Sun Y , Zhao Z , Li Q , Wang C , Ge X , Wang X , Wang G , Qin Y
Ref : J Internal Medicine Res , 48 :300060520936177 , 2020
Abstract : OBJECTIVES: To investigate whether dl-3-n-butylphthalide (NBP) affects cholinergic system function and ameliorates cognitive decline in a rat model of vascular dementia (VaD). METHODS: The VaD rat model was established by bilateral common carotid artery ligation (two-vessel occlusion, 2VO). Rats were divided into five groups: control, sham, 2VO, 2VO+NBP (80 mg/kg; intragastric), and 2VO+donepezil (1 mg/kg; intragastric). Treatments were administered once daily for 2 weeks from day 21 post-surgery. Spatial learning and memory were evaluated by Morris water maze performance. Hippocampal choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) expressions were detected using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction methods. RESULTS: The daily escape latency was significantly longer in 2VO rats than in the sham or control groups, while the time spent in the target quadrant was significantly shorter. The daily escape latency of the 2VO+NBP group was significantly shorter compared with the 2VO group. Following NBP treatment, ChAT, AChE, VAChT, and BDNF expressions were significantly upregulated in the hippocampus. CONCLUSIONS: Central cholinergic dysfunction may be involved in VaD pathogenesis. NBP treatment significantly improved spatial learning and memory in VaD rats, and may enhance cholinergic system function via BDNF-mediated neuroprotection.
ESTHER : Sun_2020_J.Int.Med.Res_48_300060520936177
PubMedSearch : Sun_2020_J.Int.Med.Res_48_300060520936177
PubMedID: 32644834

Title : miR-2382-5p Regulates Lipid Metabolism by Targeting NDRG2 in Mammary Epithelial Cells of Dairy Cattle - Xia_2020_DNA.Cell.Biol__
Author(s) : Xia L , Zhao Z , Yang R , Jiang P , Liu Y , Yu H , Bai Z , Mi J , Yu X , Fang X
Ref : DNA & Cell Biology , : , 2020
Abstract : microRNA is a class of single-stranded RNA molecules of about 22-24 nucleotides in length, which regulate a variety of biological processes, including lipid metabolism and triglyceride synthesis at transcriptional and translational levels by degrading target mRNAs or interfering with the protein production. In this study, the effect of miR-2382-5p on triglyceride levels was examined in bovine mammary epithelial cells (BMECs), and the results showed that miR-2382-5p could decrease the content of triglyceride. Furthermore, miR-2382-5p regulated the expression of lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma co-activator 1beta (PPARGC1B), hormone-sensitive lipase (HSL), and peroxisome proliferator-activated receptor gamma (PPARgamma), which are known to increase triglyceride decomposition in lipid metabolism. Luciferase reporter assay and quantitative real-time PCR (qPCR) validated that miR-2382-5p downregulated the mRNA expression of target gene N-myc downstream-regulated gene 2 (NDRG2) by specifically recognizing and binding to its 3'-untranslated region (UTR). Meanwhile, overexpression of NDRG2 led to increased triglyceride and cholesterol production in BMECs. In summary, this study suggested that miR-2382-5p regulated lipid metabolism by targeting NDRG2, which might be a potential target for molecular manipulation of milk fat composition to produce healthy milk. This study also provided basic data for further understanding lipid metabolism in dairy cattle.
ESTHER : Xia_2020_DNA.Cell.Biol__
PubMedSearch : Xia_2020_DNA.Cell.Biol__
PubMedID: 33124928

Title : Structure and characterization of Aspergillus fumigatus lipase B with a unique, oversized regulatory subdomain - Huang_2019_FEBS.J_286_2366
Author(s) : Huang W , Lan D , Popowicz GM , Zak KM , Zhao Z , Yuan H , Yang B , Wang Y
Ref : Febs J , 286 :2366 , 2019
Abstract : Fungal lipases are efficient and environment-friendly biocatalysts for many industrially relevant processes. One of the most widely applied lipases in the manufacturing industry is Candida antarctica lipase B (CALB). Here, we report the biochemical and structural characterization of a novel CALB-like lipase from an important human pathogen-Aspergillus fumigatus (AFLB), which has high sn-1,3-specificity toward triolein. AFLB crystal structure displays a CALB-like catalytic domain and hosts a unique tightly closed 'lid' domain that contains a disulfide bridge, as well as an extra N-terminal subdomain composed of residues 1-128 (including the helix alpha1-alpha5 located above the active site). To gain insight into the function of this novel lid and N-terminal subdomain, we constructed and characterized a series of mutants in these two domains. Deleting the protruding bulk lid's residues, replacing the bulk and tight lid with a small and loose lid from CALB, or breaking the disulfide bridge increased the affinity of CALB for glyceride substrates and improved its catalytic activity, along with the loss of enzyme fold stability and thermostability. N-terminal truncation mutants revealed that the N-terminal peptide (residues 1-59) is a strong inhibitor of AFLB binding to lipid films. This peptide thus limits AFLB's penetration power and specific activity, revealing a unique enzyme activity regulatory mechanism. Our findings on the functional and structural properties of AFLB provide a better understanding of the functions of the CALB-like lipases and pave the way for its future protein engineering. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 6IDY.
ESTHER : Huang_2019_FEBS.J_286_2366
PubMedSearch : Huang_2019_FEBS.J_286_2366
PubMedID: 30908847
Gene_locus related to this paper: aspfu-q4wg73

Title : Insight into the Modification of Phosphatidylcholine with n-3 Polyunsaturated Fatty Acids-Rich Ethyl Esters by Immobilized MAS1 Lipase - Wang_2019_Molecules_24_
Author(s) : Wang X , Qin X , Li X , Zhao Z , Yang B , Wang Y
Ref : Molecules , 24 : , 2019
Abstract : This study reported the modification of phosphatidylcholine (PC) with n-3 polyunsaturated fatty acids (PUFA)-rich ethyl esters (EE) by immobilized MAS1 lipase-catalyzed transesterification in the solvent-free system. Effects of n-3 PUFA-rich EE/PC mass ratio, enzyme loading, reaction temperature, and water dosage on the incorporation of n-3 PUFA into PC were investigated, respectively. The results indicate that the maximum incorporation of n-3 PUFA into PC reached 33.5% (24 h) under the following conditions: n-3 PUFA-rich EE/PC mass ratio of 6:1, enzyme loading of 20%, reaction temperature of 55 degrees C, and water dosage of 1.0%. After 72 h of reaction, the incorporation of n-3 PUFA into PC was 43.55% and the composition of the reaction mixture was analyzed by (31)P nuclear magnetic resonance (NMR). The results show that the reaction product consisted of 32.68% PC, 28.76% 1-diacyl-sn-glycero-3-lysophosphatidylcholine (sn-1 LPC), 4.90% 2-diacyl-sn-glycero-3-lysophosphatidylcholine (sn-2 LPC), and 33.60% sn-glycero-3-phosphatidylcholine (GPC). This study offers insight into the phospholipase activity of immobilized MAS1 lipase and suggests the extended applications of immobilized MAS1 lipase in the modification of phospholipids for industrial purpose.
ESTHER : Wang_2019_Molecules_24_
PubMedSearch : Wang_2019_Molecules_24_
PubMedID: 31569526
Gene_locus related to this paper: 9actn-h0b8d4

Title : Plasma cholinesterase is associated with Chinese adolescent overweight or obesity and metabolic syndrome prediction - Han_2019_Diabetes.Metab.Syndr.Obes_12_685
Author(s) : Han Y , Ma Y , Liu Y , Zhao Z , Zhen S , Yang X , Xu Z , Wen D
Ref : Diabetes Metab Syndr Obes , 12 :685 , 2019
Abstract : Purpose: To determine the plasma concentrations of butyrylcholinesterase (BChE), also known as pseudocholinesterase, in different weight categories of adolescents, and to explore the possible association between plasma BChE and overweight (OW), obesity, and metabolic syndrome (MetS) in Chinese adolescents. Patients and methods: This cross-sectional study included 1,236 Chinese adolescents (194 obese [OB], 188 OW, 732 normal weight [NW], and 122 underweight [UW]). The biochemical variables and anthropometric variables of the study participants were evaluated. Plasma BChE level was measured by DGKC method. Results: OB was associated with a higher prevalence of upper strata plasma BChE levels when compared with the BChE levels in UW, NW, and OW group. A logistic regression analysis showed that plasma BChE was positively associated with the OB group when compared with the NW group. Boys in the OW group, but not the OB group, had a significantly higher prevalence of upper stratum of BChE levels. Plasma triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and ApoB levels were positively associated with the upper stratum of BChE levels when compared with lower stratum. MetS and most of its components were more prevalent among subjects with upper stratum rather than lower stratum BChE levels. Receiver operating characteristic curves for plasma BChE in subjects with MetS indicated that the AUC was 0.80 (95%CI:0.70-0.90,P<0.001) and 0.89 (95%CI:0.82-0.95,P<0.001) in girls and boys, respectively. After adjusting for age, the multivariate-adjusted odds ratio for MetS in the upper stratum of BChE levels was 8.73 (95%CI: 3.49-21.84) in the boys cohorts and also in the girls cohorts (OR=1.71, 95%CI: 1.35-21.70). Conclusion: This study confirmed an association between BChE levels and weight status in Chinese adolescents, and demonstrated that the upper strata of plasma BChE levels were associated with being OW, and even more highly associated with obesity. Plasma BChE levels were positively associated with MetS and its components and could be useful for identifying adolescents with MetS.
ESTHER : Han_2019_Diabetes.Metab.Syndr.Obes_12_685
PubMedSearch : Han_2019_Diabetes.Metab.Syndr.Obes_12_685
PubMedID: 31190929

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

Title : Reassembly of native components with donepezil to execute dual-missions in Alzheimer's disease therapy - Zhang_2019_J.Control.Release_296_14
Author(s) : Zhang H , Zhao Y , Yu M , Zhao Z , Liu P , Cheng H , Ji Y , Jin Y , Sun B , Zhou J , Ding Y
Ref : J Control Release , 296 :14 , 2019
Abstract : Alzheimer's disease (AD) is a multifaceted and progressive neurodegenerative disease characterized by accumulation of amyloid-beta (Abeta) and deficits of acetylcholine. Accordingly, the intra-/extra-cerebral level of high density lipoprotein (HDL) is crucial on the pathogenesis of AD; and most of all, various HDL-protein subtypes play a double-edged role in AD pathology, of which apolipoprotein A-I (apoA-I) gives protective outcomes. Inspired from "HDL bionics", we proposed biologically reassembled nanodrugs, donepezil-loaded apolipoprotein A-I-reconstituted HDL (rHDL/Do) that concurrently executed dual-missions of Abeta-targeting clearance and acetylcholinesterase (AChE) inhibition in AD therapy. Once prepared, rHDL/Do nanodrug achieved high drug encapsulation efficiency of 90.47%, and mimicked the configurations and properties of natural lipoproteins aiming to significantly enhance BBB penetration and modulate Abeta-induced neuronal damage both in vitro and in vivo. Surface plasmon resonance (SPR) analysis confirmed that rHDL/Do facilitated microglial-mediated Abeta intake and degradation, demonstrating low KD value with Abeta affinity (2.45x10(-8) of Abeta monomer and 2.78x10(-8) of Abeta oligomer). In AD animal models, daily treatment of rHDL/Do efficiently inhibited AChE activity, ameliorated neurologic variation, promoted Abeta clearance, and rescued memory loss at a safe level. The collective findings indicated that the biological nanodrug was provided with the capacities of BBB penetration, Abeta capture and degradation via microglial cells, and cholinergic dysfunction amelioration after controlled donepezil release. In summary, rHDL/Do nanodrugs could offer a promising strategy to synergize both symptom control and disease modification in AD therapy.
ESTHER : Zhang_2019_J.Control.Release_296_14
PubMedSearch : Zhang_2019_J.Control.Release_296_14
PubMedID: 30639387

Title : A Thermostable Monoacylglycerol Lipase from Marine Geobacillus sp. 12AMOR1: Biochemical Characterization and Mutagenesis Study - Tang_2019_Int.J.Mol.Sci_20_
Author(s) : Tang W , Lan D , Zhao Z , Li S , Li X , Wang Y
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Lipases with unique substrate specificity are highly desired in biotechnological applications. In this study, a putative marine Geobacillus sp. monoacylglycerol lipase (GMGL) encoded gene was identified by a genomic mining strategy. The gene was expressed in Escherichia coli as a His-tag fusion protein and purified by affinity chromatography with a yield of 264 mg per liter fermentation broth. The recombinant GMGL shows the highest hydrolysis activity at 60 degrees C and pH 8.0, and the half-life was 60 min at 70 degrees C. The GMGL is active on monoacylglycerol (MAG) substrate but not diacylglycerol (DAG) or triacylglycerol (TAG), and produces MAG as the single product in the esterification reaction. Modeling structure analysis showed that the catalytic triad is formed by Ser97, Asp196 and His226, and the flexible cap region is constituted by residues from Ala120 to Thr160. A mutagenesis study on Leu142, Ile145 and Ile170 located in the substrate binding tunnel revealed that these residues were related with its substrate specificity. The kcat/Km value toward the pNP-C6 substrate in mutants Leu142Ala, Ile145Ala and Ile170Phe increased to 2.3-, 1.4- and 2.2-fold as compared to that of the wild type, respectively.
ESTHER : Tang_2019_Int.J.Mol.Sci_20_
PubMedSearch : Tang_2019_Int.J.Mol.Sci_20_
PubMedID: 30759774
Gene_locus related to this paper: 9baci-a0a0g3xxb4

Title : Biodegradation of mycotoxin fumonisin B1 by a novel bacterial consortium SAAS79 - Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
Author(s) : Zhao Z , Zhang Y , Gong A , Liu N , Chen S , Zhao X , Li X , Chen L , Zhou C , Wang J
Ref : Applied Microbiology & Biotechnology , 103 :7129 , 2019
Abstract : Fumonisin B1 (FB1) contamination in cereals and cereal products remains an important aspect of food safety because of its wide distribution and the potential health hazard. However, only a few microorganisms have been reported to effectively degrade FB1. In this present study, a bacterial consortium SAAS79 with highly FB1-degrading activity was isolated from the spent mushroom compost. The combination of antibiotic-driven selection and 16S rDNA sequencing identified the Pseudomonas genus as the key FB1-degrading member. The microbial consortium could degrade more than 90% of 10 microg/mL FB1 after incubation for 24 h at pH of 5-7 and temperature of 28-35 degreesC. The enzymes from the intracellular space were proved to be responsible for FB1 degradation, which eliminated about 90% of 10 microg/mL FB1 in 3 h. Besides, liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) analysis identified two degradation products of FB1, and their toxicity on the monkey kidney cells (MARC-145) was significantly lower (p < 0.05) compared with the parent FB1. Overall, the consortium SAAS79 and its crude enzymes may be a potential choice for the decontamination of FB1 in the feed and food industry. Also, the bacterial consortium provides a new source of genes for the development of enzymatic detoxification agent.
ESTHER : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedSearch : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedID: 31230101

Title : Bioaccumulation and toxicity of methoxychlor on Chinese mitten crab (Eriocheir sinensis) - Cheng_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_221_89
Author(s) : Cheng L , Song W , Rao Q , Zhou J , Zhao Z
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , 221 :89 , 2019
Abstract : Chinese mitten crab, a featured macrobenthos, has been one of the most important economical aquatic species in China. This study assessed the accumulation of an organochlorine pesticide methoxychlor (MXC) in Chinese mitten crab during exposure to 1mg/L of MXC. The results showed the residual concentration of MXC in the ovary and hepatopancreas reached 55.07+/-2.64ng/g and 34.51+/-2.35ng/g, respectively. After exposure, tubular vacuolization of epithelial tissues, condensed egg cells and obvious intervals between egg cell wall and stroma were observed in the hepatopancreas and ovary, respectively. Significant changes of three key metabolic enzymes in hepatopancreas were observed upon exposure to MXC. Compared to the control, acetylcholinesterase level was significantly higher at day 7 (0.15+/-0.01 vs. 0.06+/-0.00U/mgprot); glutathione S-transferase level was elevated at both day 4 (12.01+/-0.48 vs. 3.20+/-0.44U/mgprot) and day 7 (12.84+/-1.01 vs. 8.22+/-0.81U/mgprot); superoxide dismutase was sharply increased at day 4 (21.20+/-0.24 vs. 3.66+/-0.60U/mgprot) but decreased at day 7 (3.74+/-0.12 vs. 9.44+/-0.85U/mgprot). Overall, dissolved MXC accumulated in lipid-rich tissues could cause damages on epithelial cells and egg cells and change metabolic activities of enzymes involved in antioxidative stress and detoxification processes.
ESTHER : Cheng_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_221_89
PubMedSearch : Cheng_2019_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_221_89
PubMedID: 30954688

Title : Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways - Li_2019_Biol.Res_52_10
Author(s) : Li W , Yu X , Zhu C , Wang Z , Zhao Z , Li Y , Zhang Y
Ref : Biol Res , 52 :10 , 2019
Abstract : BACKGROUND: Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. METHODS: 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, alpha-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. RESULTS: Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. CONCLUSIONS: Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment.
ESTHER : Li_2019_Biol.Res_52_10
PubMedSearch : Li_2019_Biol.Res_52_10
PubMedID: 30871618
Gene_locus related to this paper: human-NOTUM

Title : Ophiosphaerellins A-I, Polyketide-Derived Compounds from the Endolichenic Fungus Ophiosphaerella korrae - Li_2018_ACS.Omega_3_176
Author(s) : Li Y , Zhu R , Zhang J , Xie F , Wang X , Xu K , Qiao Y , Zhao Z , Lou H
Ref : ACS Omega , 3 :176 , 2018
Abstract : Ophiosphaerellins A-I (1-9), the first example of bicyclo[4.1.0]heptenones, as well as their biosynthetic relatives ophiosphaerekorrins A-B (10-11) were isolated from the endolichenic fungus Ophiosphaerella korrae. Biosynthetically, they were derived from the polyketide pathway, and their absolute configurations were determined on the basis of the combination analysis of spectral data, circular dichroism calculations, and single-crystal X-ray diffraction measurement. Preliminary test with thin-layer chromatography bioautography found that this type of compounds showed moderate acetylcholinesterase (AChE) inhibitory effects.
ESTHER : Li_2018_ACS.Omega_3_176
PubMedSearch : Li_2018_ACS.Omega_3_176
PubMedID: 30023771

Title : Multifunctional Roles of Plant Cuticle During Plant-Pathogen Interactions - Ziv_2018_Front.Plant.Sci_9_1088
Author(s) : Ziv C , Zhao Z , Gao YG , Xia Y
Ref : Front Plant Sci , 9 :1088 , 2018
Abstract : In land plants the cuticle is the outermost layer interacting with the environment. This lipophilic layer comprises the polyester cutin embedded in cuticular wax; and it forms a physical barrier to protect plants from desiccation as well as from diverse biotic and abiotic stresses. However, the cuticle is not merely a passive, mechanical shield. The increasing research on plant leaves has addressed the active roles of the plant cuticle in both local and systemic resistance against a variety of plant pathogens. Moreover, the fruit cuticle also serves as an important determinant of fruit defense and quality. It shares features with those of vegetative organs, but also exhibits specific characteristics, the functions of which gain increasing attention in recent years. This review describes multiple roles of plant cuticle during plant-pathogen interactions and its responses to both leaf and fruit pathogens. These include the dynamic changes of plant cuticle during pathogen infection; the crosstalk of cuticle with plant cell wall and diverse hormone signaling pathways for plant disease resistance; and the major biochemical, molecular, and cellular mechanisms that underlie the roles of cuticle during plant-pathogen interactions. Although research developments in the field have greatly advanced our understanding of the roles of plant cuticle in plant defense, there still remain large gaps in our knowledge. Therefore, the challenges thus presented, and future directions of research also are discussed in this review.
ESTHER : Ziv_2018_Front.Plant.Sci_9_1088
PubMedSearch : Ziv_2018_Front.Plant.Sci_9_1088
PubMedID: 30090108

Title : A novel strategy to improve the thermostability of Penicillium camembertii mono- and di-acylglycerol lipase - Liu_2018_Biochem.Biophys.Res.Commun_500_639
Author(s) : Liu Y , Yuan D , Zhao Z , Lan D , Yang B , Wang Y
Ref : Biochemical & Biophysical Research Communications , 500 :639 , 2018
Abstract : Penicillium camembertii (PCL), a mono- and di-acylglycerol lipase (DGL), has the vital potential in the oil chemistry for food industry. However, known DGLs are mesophilic enzymes which restricts its application in the industry. To improve thermostability of PCL, we used amino acid substitution by comparison of amino acids compositions of PCL and protein sequences from typical thermophilic bacteria. Then, some conservative residues around active center were avoided to mutate according to homologous alignment analyses. Furthermore, the list was narrowed down to 28 candidate mutational sites of PCL by analyzing the hydrophobic interaction of amino acids in the structure. And among them only the mutant PCL-D25R had formed an additional salt bridge between R25-D32 and increased more hydrogen bonds interaction. Therefore, mutant PCL-D25R were constructed and expressed. Thermal inactivation assay showed that the half-life of mutant PCL-D25R at 45 degrees C increased 4-fold compared to that of PCL-WT. Melting temperature of mutant PCL-D25R increased to 49.5 degrees C from 46.5 degrees C by fluorescence-based thermal stability assay. This study provides a valuable strategy for engineering DGL thermostability.
ESTHER : Liu_2018_Biochem.Biophys.Res.Commun_500_639
PubMedSearch : Liu_2018_Biochem.Biophys.Res.Commun_500_639
PubMedID: 29679572
Gene_locus related to this paper: penca-mdgli

Title : Crystal structure of a lipase from Streptomyces sp. strain W007 - implications for thermostability and regiospecificity - Zhao_2017_FEBS.J_284_3506
Author(s) : Zhao Z , Hou S , Lan D , Wang X , Liu J , Khan FI , Wang Y
Ref : Febs J , 284 :3506 , 2017
Abstract : MAS1 from marine Streptomyces sp. strain W007 belongs to the bacterial lipase I.7 subfamily and is characterized as a thermostable and nonregiospecific lipase. To shed light on the catalytic mechanism of MAS1, we determined its crystal structure with closed conformation in two crystal forms at 2.3 A resolution. MAS1 adopts the canonical alpha/beta hydrolase core fold with its catalytic triad being formed by S109, D200 and H232. Structural analysis and biochemical assays revealed that disulfide bonds and salt bridges play a vital role in the thermostability of MAS1. In addition, we discovered that the replacement of H108 with a tryptophan converts MAS1 from a nonregiospecific to an sn-1,3-specific lipase, suggesting the functional importance of the second position from the conserved pentapeptide motif in defining the regiospecificity of MAS1. Our present study provides insights into the molecular basis for the thermostability and regiospecificity of MAS1, and it may aid in the rational design of thermostable or regiospecific lipases for potential industrial applications. DATABASE: Structural data are available in the Protein Data Bank database under the accession numbers 5H6B and 5H6G.
ESTHER : Zhao_2017_FEBS.J_284_3506
PubMedSearch : Zhao_2017_FEBS.J_284_3506
PubMedID: 28857479
Gene_locus related to this paper: 9actn-h0b8d4

Title : Recombinant Lipase from Gibberella zeae Exhibits Broad Substrate Specificity: A Comparative Study on Emulsified and Monomolecular Substrate - Wang_2017_Int.J.Mol.Sci_18_
Author(s) : Wang F , Zhang H , Zhao Z , Wei R , Yang B , Wang Y
Ref : Int J Mol Sci , 18 : , 2017
Abstract : Using the classical emulsified system and the monomolecular film technique, the substrate specificity of recombinant Gibberella zeae lipase (rGZEL) that originates from Gibberella zeae was characterized in detail. Under the emulsified reaction system, both phospholipase and glycolipid hydrolytic activities were observed, except for the predominant lipase activity. The optimum conditions for different activity exhibition were also determined. Compared with its lipase activity, a little higher ratio of glycolipid hydrolytic activity (0.06) than phospholipase activity (0.02) was found. rGZEL preferred medium chain-length triglycerides, while lower activity was found for the longer-chain triglyceride. Using the monomolecular film technique, we found that the preference order of rGZEL to different phospholipids was 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS) > 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (PG) > 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) > l-alpha-phosphatidylinositol (PI) > cardiolipin (CL) > 3-sn-phosphatidic acid sodium salt (PA) > l-alpha-phosphatidylethanolamine (PE), while no hydrolytic activity was detected for sphingomyelin (SM). Moreover, rGZEL showed higher galactolipase activity on 1,2-distearoyimonoglactosylglyceride (MGDG). A kinetic study on the stereo- and regioselectivity of rGZEL was also performed by using three pairs of pseudodiglyceride enantiomers (DDGs). rGZEL presented higher preference for distal DDG enantiomers than adjacent ester groups, however, no hydrolytic activity to the sn-2 position of diglyceride analogs was found. Furthermore, rGZEL preferred the R configuration of DDG enantiomers. Molecular docking results were in concordance with in vitro tests.
ESTHER : Wang_2017_Int.J.Mol.Sci_18_
PubMedSearch : Wang_2017_Int.J.Mol.Sci_18_
PubMedID: 28718792
Gene_locus related to this paper: gibze-q6wer3

Title : The Lid Domain in Lipases: Structural and Functional Determinant of Enzymatic Properties - Khan_2017_Front.Bioeng.Biotechnol_5_16
Author(s) : Khan FI , Lan D , Durrani R , Huan W , Zhao Z , Wang Y
Ref : Front Bioeng Biotechnol , 5 :16 , 2017
Abstract : Lipases are important industrial enzymes. Most of the lipases operate at lipid-water interfaces enabled by a mobile lid domain located over the active site. Lid protects the active site and hence responsible for catalytic activity. In pure aqueous media, the lid is predominantly closed, whereas in the presence of a hydrophobic layer, it is partially opened. Hence, the lid controls the enzyme activity. In the present review, we have classified lipases into different groups based on the structure of lid domains. It has been observed that thermostable lipases contain larger lid domains with two or more helices, whereas mesophilic lipases tend to have smaller lids in the form of a loop or a helix. Recent developments in lipase engineering addressing the lid regions are critically reviewed here. After on, the dramatic changes in substrate selectivity, activity, and thermostability have been reported. Furthermore, improved computational models can now rationalize these observations by relating it to the mobility of the lid domain. In this contribution, we summarized and critically evaluated the most recent developments in experimental and computational research on lipase lids.
ESTHER : Khan_2017_Front.Bioeng.Biotechnol_5_16
PubMedSearch : Khan_2017_Front.Bioeng.Biotechnol_5_16
PubMedID: 28337436

Title : A comparative study on kinetics and substrate specificities of Phospholipase A1 with Thermomyces lanuginosus lipase - Xin_2017_J.Colloid.Interface.Sci_488_149
Author(s) : Xin R , Khan FI , Zhao Z , Zhang Z , Yang B , Wang Y
Ref : J Colloid Interface Sci , 488 :149 , 2017
Abstract : The mechanism of lipase binding to the lipid-water interface is crucial for substrate specificity and kinetic properties. In this study, the chain-length specificity, regiospecificity and substrate specificity of Phospholipase A1 (PLA1) and its parent enzyme Thermomyces lanuginosus lipase (TLL) have been investigated using a classical emulsion system. The results show that both PLA1 and TLL are 1,3-regioselective lipases. Additionally, the hydrolytic activity of PLA1 is comparatively lower on short-chain triacylglyceride (TAG) and higher on phosphatidylcholine (PC) than the hydrolytic activity of TLL. Further, the results obtained with monolayer film techniques demonstrate that the C-terminal region regulates the binding of PLA1 to PC. A hypothesis is presented according to which the alpha9 helix of C-terminal region in PLA1 not only controls the opening of lid but also serves as a membrane anchor that assists in binding to PC. These findings bring new insight into rational design of novel lipases with intriguing functionalities.
ESTHER : Xin_2017_J.Colloid.Interface.Sci_488_149
PubMedSearch : Xin_2017_J.Colloid.Interface.Sci_488_149
PubMedID: 27821336

Title : Identification of the bovine HSL gene expression profiles and its association with fatty acid composition and fat deposition traits - Fang_2017_Meat.Sci_131_107
Author(s) : Fang X , Zhao Z , Jiang P , Yu H , Xiao H , Yang R
Ref : Meat Sci , 131 :107 , 2017
Abstract : Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of hydrolysing a variety of esters and is considered to be a candidate gene affecting fat deposition traits. Gene expression profiles of HSL were analysed in various adipose tissues of cattle, and the effect of HSL on lipid metabolism genes was analysed by a PCR array. Novel polymorphisms were identified within the HSL regulatory domain by sequencing, and the relationship between HSL variants and fat deposition traits was analysed. HSL mRNA was highly expressed in the subcutaneous and visceral fat of cattle. CPT1B/CPT1C and other lipocatabolic genes were upregulated, and lipogenesis-related genes (FASN, LPL and ACOT12) were downregulated by HSL overexpression in BFFs. Five novel variants in the HSL functional domain were significantly associated with fat deposition traits, including FCR, LBT, MFW and fatty acid composition. HSL plays a pivotal role in the regulation of lipolysis and fatty acid biosynthesis in beef cattle.
ESTHER : Fang_2017_Meat.Sci_131_107
PubMedSearch : Fang_2017_Meat.Sci_131_107
PubMedID: 28501436

Title : Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial - Xiao_2017_Age.Ageing__1
Author(s) : Xiao S , Wang T , Ma X , Qin Y , Li X , Zhao Z , Liu X , Wang X , Xie H , Jiang Q , Sun L , Luo B , Shang L , Chen W , Bai Y , Tang M , He M , Wu L , Ma Q , Hou D , He J
Ref : Age Ageing , :1 , 2017
Abstract : Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.
ESTHER : Xiao_2017_Age.Ageing__1
PubMedSearch : Xiao_2017_Age.Ageing__1
PubMedID: 28419192

Title : Inhibition behavior of fructus psoraleae's ingredients towards human carboxylesterase 1 (hCES1) - Sun_2016_Xenobiotica_46_503
Author(s) : Sun DX , Ge GB , Dong PP , Cao YF , Fu ZW , Ran RX , Wu X , Zhang YY , Hua HM , Zhao Z , Fang ZZ
Ref : Xenobiotica , 46 :503 , 2016
Abstract : 1. Fructus psoraleae (FP) is the dried ripe seeds of Psoralea corylifolia L. (Fabaceae) widely used in Asia, and has been reported to exert important biochemical and pharmacological activities. The adverse effects of FP remain unclear. The present study aims to determine the inhibition of human carboxylesterase 1 (CES1) by FP's major ingredients, including neobavaisoflavone, corylifolinin, coryfolin, psoralidin, corylin and bavachinin. 2. The probe substrate of CES1 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) was derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT), and human liver microsomes (HLMs)-catalyzed BMBT metabolism was used to phenotype the activity of CES1. In silico docking method was employed to explain the inhibition mechanism. 3. All the tested compounds exerted strong inhibition towards the activity of CES1 in a concentration-dependent behavior. Furthermore, the inhibition kinetics was determined for the inhibition of neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin towards CES1. Both Dixon and Lineweaver-Burk plots showed that neobavaisoflavone, corylifolinin, coryfolin and corylin noncompetitively inhibited the activity of CES1, and bavachinin competitively inhibited the activity of CES1. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 9.4, 1.9, 0.7 and 0.5 muM for neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin, respectively. In conclusion, the inhibition behavior of CES1 by the FP's constituents was given in this article, indicating the possible adverse effects of FP through the disrupting CES1-catalyzed metabolism of endogenous substances and xenobiotics.
ESTHER : Sun_2016_Xenobiotica_46_503
PubMedSearch : Sun_2016_Xenobiotica_46_503
PubMedID: 26560012

Title : Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma - Zhang_2016_Int.Urol.Nephrol_48_1993
Author(s) : Zhang B , Shen C , Jin J , Song Y , Zhao Z , Zhang X , Wang G , Fan Y , Mi Y , Hu S , Cui Y , Zhou L , He Z , Yu W , Han W
Ref : International Urology & Nephrology , 48 :1993 , 2016
Abstract : PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown.
METHODS: A total of 180 patients who underwent radical nephroureterectomy (RNU) for UTUC were included in this retrospective analysis. The associations of pretreatment serum PChE levels with clinicopathological characteristics and clinical outcomes were assessed.
RESULTS: The median (IQR) pretreatment serum PChE level was 6385 (5449-7260) IU/L, and an optimal cutoff value of 5336 IU/L was set according to ROC analysis. Decreased pretreatment serum PChE levels were significantly correlated with older patient age, higher preoperative chronic kidney disease (CKD) stage and pT stage (all P < 0.05). On multivariate analysis, adjusting for preoperative variables, decreased pretreatment serum PChE levels independently predicted higher pT stage (P = 0.011). Moreover, Kaplan-Meier curves suggested that patients with PChE levels <5336 IU/L were predicted to have a shorter overall survival (OS) and cancer-specific survival (CSS) than those with PChE levels >/=5336 IU/L (both P < 0.001). On multivariate analysis, decreased pretreatment serum PChE levels were significantly associated with shorter OS (HR 0.553; 95 %CI 0.322-0.951; P = 0.032) and CSS (HR 0.484; 95 %CI 0.269-0.870; P = 0.015).
CONCLUSIONS: Decreased pretreatment serum PChE level is an independent predictor for higher pT stage, shorter OS and CSS in patients with UTUC. Pretreatment serum PChE levels may act as a simple and effective parameter to predict prognosis for UTUC patients after RNU.
ESTHER : Zhang_2016_Int.Urol.Nephrol_48_1993
PubMedSearch : Zhang_2016_Int.Urol.Nephrol_48_1993
PubMedID: 27554671

Title : A novel esterase from a marine mud metagenomic library for biocatalytic synthesis of short-chain flavor esters - Gao_2016_Microb.Cell.Fact_15_41
Author(s) : Gao W , Wu K , Chen L , Fan H , Zhao Z , Gao B , Wang H , Wei D
Ref : Microb Cell Fact , 15 :41 , 2016
Abstract : BACKGROUND: Marine mud is an abundant and largely unexplored source of enzymes with unique properties that may be useful for industrial and biotechnological purposes. However, since most microbes cannot be cultured in the laboratory, a cultivation-independent metagenomic approach would be advantageous for the identification of novel enzymes. Therefore, with the objective of screening novel lipolytic enzymes, a metagenomic library was constructed using the total genomic DNA extracted from marine mud.
RESULTS: Based on functional heterologous expression, 34 clones that showed lipolytic activity were isolated. The five clones with the largest halos were identified, and the corresponding genes were successfully overexpressed in Escherichia coli. Molecular analysis revealed that these encoded proteins showed 48-79 % similarity with other proteins in the GenBank database. Multiple sequence alignment and phylogenetic tree analysis classified these five protein sequences as new members of known families of bacterial lipolytic enzymes. Among them, EST4, which has 316 amino acids with a predicted molecular weight of 33.8 kDa, was further studied in detail due to its strong hydrolytic activity. Characterization of EST4 indicated that it is an alkaline esterase that exhibits highest hydrolytic activity towards p-nitrophenyl butyrate (specific activity: 1389 U mg(-1)) at 45 degrees C and pH 8.0. The half-life of EST4 is 55 and 46 h at 40 and 45 degrees C, respectively, indicating a relatively high thermostability. EST4 also showed remarkable stability in organic solvents, retaining 90 % of its initial activity when incubated for 12 h in the presence of hydrophobic alkanes. Furthermore, EST4 was used as an efficient whole-cell biocatalyst for the synthesis of short-chain flavor esters, showing high conversion rate and good tolerance for high substrate concentrations (up to 3.0 M). These results demonstrate a promising potential for industrial scaling-up to produce short-chain flavor esters at high substrate concentrations in non-aqueous media.
CONCLUSIONS: This manuscript reports unprecedented alcohol tolerance and conversion of an esterase biocatalyst identified from a marine mud metagenomic library. The high organic solvent tolerance and thermostability of EST4 suggest that it has great potential as a biocatalyst.
ESTHER : Gao_2016_Microb.Cell.Fact_15_41
PubMedSearch : Gao_2016_Microb.Cell.Fact_15_41
PubMedID: 26892801

Title : Conifer flavonoid compounds inhibit detoxification enzymes and synergize insecticides - Wang_2016_Pestic.Biochem.Physiol_127_1
Author(s) : Wang Z , Zhao Z , Cheng X , Liu S , Wei Q , Scott IM
Ref : Pestic Biochem Physiol , 127 :1 , 2016
Abstract : Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase inhibitors from phytochemicals could provide potential new insecticide synergists. Conifer tree species contain flavonoids, such as taxifolin, that inhibit in vitro GST activity. The objectives were to test the relative effectiveness of taxifolin as an enzyme inhibitor and as an insecticide synergist in combination with the organophosphorous insecticide, Guthion (50% azinphos-methyl), and the botanical insecticide, pyrethrum, using an insecticide-resistant Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say) strain. Both taxifolin and its isomer, quercetin, increased the mortality of 1(st) instar CPB larvae after 48h when combined with Guthion, but not pyrethrum. Taxifolin had greater in vitro esterase inhibition compared with the commonly used esterase inhibitor, S, S, S-tributyl phosphorotrithioate (DEF). An in vivo esterase and GST inhibition effect after ingestion of taxifolin was measured, however DEF caused a greater suppression of esterase activity. This study demonstrated that flavonoid compounds have both in vitro and in vivo esterase inhibition, which is likely responsible for the insecticide synergism observed in insecticide-resistant CPB.
ESTHER : Wang_2016_Pestic.Biochem.Physiol_127_1
PubMedSearch : Wang_2016_Pestic.Biochem.Physiol_127_1
PubMedID: 26821651

Title : Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes - Li_2016_J.Med.Chem_59_6772
Author(s) : Li S , Xu H , Cui S , Wu F , Zhang Y , Su M , Gong Y , Qiu S , Jiao Q , Qin C , Shan J , Zhang M , Wang J , Yin Q , Xu M , Liu X , Wang R , Zhu L , Li J , Xu Y , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 59 :6772 , 2016
Abstract : Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.
ESTHER : Li_2016_J.Med.Chem_59_6772
PubMedSearch : Li_2016_J.Med.Chem_59_6772
PubMedID: 27396490
Gene_locus related to this paper: human-DPP4

Title : Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes - Wu_2016_ACS.Med.Chem.Lett_7_498
Author(s) : Wu WL , Hao J , Domalski M , Burnett DA , Pissarnitski D , Zhao Z , Stamford A , Scapin G , Gao YD , Soriano A , Kelly TM , Yao Z , Powles MA , Chen S , Mei H , Hwa J
Ref : ACS Med Chem Lett , 7 :498 , 2016
Abstract : In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c.
ESTHER : Wu_2016_ACS.Med.Chem.Lett_7_498
PubMedSearch : Wu_2016_ACS.Med.Chem.Lett_7_498
PubMedID: 27190600
Gene_locus related to this paper: human-DPP4

Title : The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress - Jiang_2016_Cell.Rep_16_1502
Author(s) : Jiang F , Wang X , Wang B , Chen L , Zhao Z , Waterfield NR , Yang G , Jin Q
Ref : Cell Rep , 16 :1502 , 2016
Abstract : Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells.sHere, we report a detailed investigation of a P.saeruginosa H2-T6SS-dependent phospholipase effector, TplE, which acts as a trans-kingdom toxin. Delivery of TplE to the periplasmic space of rival bacteria leads to growth inhibition. Importantly, TplE, also contains a eukaryotic PGAP1-like domain, which targets the host ER apparatus, ultimately leading to disruption of the ER. TplE activity leads to the activation of the unfolded protein response (UPR) through the IRE1alpha-XBP1 pathway, enhancing autophagic flux. These findings indicate that this T6SS-delivered phospholipase effector is active against both prokaryotic and eukaryotic cellular targets, highlighting the T6SS as a versatile weapon in the Pseudomonas arsenal.
ESTHER : Jiang_2016_Cell.Rep_16_1502
PubMedSearch : Jiang_2016_Cell.Rep_16_1502
PubMedID: 27477276
Gene_locus related to this paper: pseae-PA1510

Title : Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis - Zhao_2016_Eur.J.Clin.Pharmacol_72_1195
Author(s) : Zhao Z , Li X , Sun S , Mei S , Ma N , Miao Z , Zhao M , Peng S
Ref : European Journal of Clinical Pharmacology , 72 :1195 , 2016
Abstract : PURPOSE: Recurrent ischemic events in Chinese patients with symptomatic extracranial or intracranial stenosis caused by aspirin or clopidogrel resistance are well known. We aimed to identify the contribution of genetic variants to the events. METHODS: Patients with symptomatic extracranial or intracranial stenosis receiving dual antiplatelet treatment for at least 5 days were enrolled in this study. The primary endpoint was a composite of ischemic events, including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality. Twenty-four single nucleotide polymorphisms (SNPs) were assessed and genotyped. The clinical characteristics of enrolled patients were collected from medical records. The influence of genetic polymorphisms on the recurrent ischemic events of the patients was examined. RESULTS: A total of 377 patients were included. During a 12-month follow-up, the composite primary endpoint was observed in 64 patients. The CYP2C19*3 (rs4986893) may increase the occurrence of the primary composite endpoint (OR = 2.56, 95 % CI = 1.29-5.10, P = 0.007), and the mutation of CES1 rs8192950 was associated with the decreased recurrence of ischemic events (OR = 0.53, 95 % CI = 0.30-0.94, P = 0.029). The other SNPs that were tested did not have statistically significant associations with the composite endpoint. CONCLUSIONS: For Chinese patients with symptomatic extracranial or intracranial stenosis treated with clopidogrel, CYP2C19*3 mutation was associated with an increased risk of ischemic events, and the mutation of rs8192950 in CES1 is associated with a decreased risk of recurrent ischemic events. Testing these two SNPs could be of value in the identification of patients at risk for recurrent ischemic events.
ESTHER : Zhao_2016_Eur.J.Clin.Pharmacol_72_1195
PubMedSearch : Zhao_2016_Eur.J.Clin.Pharmacol_72_1195
PubMedID: 27450232
Gene_locus related to this paper: human-CES1

Title : Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors - Pissarnitski_2016_Bioorg.Med.Chem_24_5534
Author(s) : Pissarnitski DA , Zhao Z , Cole D , Wu WL , Domalski M , Clader JW , Scapin G , Voigt J , Soriano A , Kelly T , Powles MA , Yao Z , Burnett DA
Ref : Bioorganic & Medicinal Chemistry , 24 :5534 , 2016
Abstract : Molecular modeling of unbound tricyclic guanine scaffolds indicated that they can serve as effective bioisosteric replacements of xanthines. This notion was further confirmed by a combination of X-ray crystallography and SAR studies, indicating that tricyclic guanine DPP4 inhibitors mimic the binding mode of xanthine inhibitors, exemplified by linagliptin. Realization of the bioisosteric relationship between these scaffolds potentially will lead to a wider application of cyclic guanines as xanthine replacements in drug discovery programs for a variety of biological targets. Newly designed DPP4 inhibitors achieved sub-nanomolar potency range and demonstrated oral activity in vivo in mouse glucose tolerance test.
ESTHER : Pissarnitski_2016_Bioorg.Med.Chem_24_5534
PubMedSearch : Pissarnitski_2016_Bioorg.Med.Chem_24_5534
PubMedID: 27670099
Gene_locus related to this paper: human-DPP4

Title : Complete Genome Sequence of Cronobacter sakazakii Strain CMCC 45402 - Zhao_2014_Genome.Announc_2_e01139
Author(s) : Zhao Z , Wang L , Wang B , Liang H , Ye Q , Zeng M
Ref : Genome Announc , 2 :e01139 , 2014
Abstract : Cronobacter sakazakii is considered to be an important pathogen involved in life-threatening neonatal infections. Here, we report the annotated complete genome sequence of C. sakazakii strain CMCC 45402, obtained from a milk sample in China. The major findings from the genomic analysis provide a better understanding of the isolates from China.
ESTHER : Zhao_2014_Genome.Announc_2_e01139
PubMedSearch : Zhao_2014_Genome.Announc_2_e01139
PubMedID: 24435860
Gene_locus related to this paper: cros8-a7mle4 , cros8-a7mft0 , 9entr-k7zz64

Title : Neuroligin-associated microRNA-932 targets actin and regulates memory in the honeybee - Cristino_2014_Nat.Commun_5_5529
Author(s) : Cristino AS , Barchuk AR , Freitas FC , Narayanan RK , Biergans SD , Zhao Z , Simoes ZL , Reinhard J , Claudianos C
Ref : Nat Commun , 5 :5529 , 2014
Abstract : Increasing evidence suggests small non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) control levels of mRNA expression during experience-related remodelling of the brain. Here we use an associative olfactory learning paradigm in the honeybee Apis mellifera to examine gene expression changes in the brain during memory formation. Brain transcriptome analysis reveals a general downregulation of protein-coding genes, including asparagine synthetase and actin, and upregulation of ncRNAs. miRNA-mRNA network predictions together with PCR validation suggest miRNAs including miR-210 and miR-932 target the downregulated protein-coding genes. Feeding cholesterol-conjugated antisense RNA to bees results in the inhibition of miR-210 and of miR-932. Loss of miR-932 impairs long-term memory formation, but not memory acquisition. Functional analyses show that miR-932 interacts with Act5C, providing evidence for direct regulation of actin expression by an miRNA. An activity-dependent increase in miR-932 expression may therefore control actin-related plasticity mechanisms and affect memory formation in the brain.
ESTHER : Cristino_2014_Nat.Commun_5_5529
PubMedSearch : Cristino_2014_Nat.Commun_5_5529
PubMedID: 25409902

Title : Sequencing, annotation, and characterization of the influenza ferret infectome - Leon_2013_J.Virol_87_1957
Author(s) : Leon AJ , Banner D , Xu L , Ran L , Peng Z , Yi K , Chen C , Xu F , Huang J , Zhao Z , Lin Z , Huang SH , Fang Y , Kelvin AA , Ross TM , Farooqui A , Kelvin DJ
Ref : J Virol , 87 :1957 , 2013
Abstract : Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naive animals was subjected to next-generation sequencing, followed by de novo data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas.
ESTHER : Leon_2013_J.Virol_87_1957
PubMedSearch : Leon_2013_J.Virol_87_1957
PubMedID: 23236062
Gene_locus related to this paper: muspf-m1ejm3 , muspf-m3xwe4 , muspf-m3y1u3 , muspf-m3y1w0 , muspf-m3yex5 , muspf-m3ywm4 , muspf-m3yzl3 , muspf-g9kcw3 , muspf-m1efe2 , muspf-g9kdq4 , muspf-m3z0x2 , muspf-g9khi6 , muspf-m3yaj5 , muspf-g9k8i1 , muspf-m3xnu7 , muspf-m3yi69 , muspf-m3ywu1 , muspf-m3yy03 , muspf-g9l4j3 , muspf-m1ejz6

Title : Chromogenic platform based on recombinant Drosophila melanogaster acetylcholinesterase for visible unidirectional assay of organophosphate and carbamate insecticide residues - Han_2012_Anal.Chim.Acta_720_126
Author(s) : Han Z , Chi C , Bai B , Liu G , Rao Q , Peng S , Liu H , Zhao Z , Zhang D , Wu A
Ref : Anal Chim Acta , 720 :126 , 2012
Abstract : In this study we propose a chromogenic platform for rapid analysis of organophosphate (OP) and carbamate (CM) insecticide residues, based on recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and indoxyl acetate as substrate. The visible chromogenic strip had the advantages identical to those of commonly used lateral flow assays (LFAs) with utmost simplicity in sample loading and result observation. After optimization, depending on the color intensity (CI) values, the well-established assay has the capabilities of both qualitative measurement via naked eyes and quantitative analysis by colorimetric reader with the desirable IC(50) values against the tested six insecticides (0.06 mug mL(-1) of carbofuran, 0.28 mug mL(-1) of methomyl, 0.03 mug mL(-1) of dichlorvos, 31.6 mug mL(-1) of methamidophos, 2.0 mug mL(-1) of monocrotophos, 6.3 mug mL(-1) of omethoate). Acceptable matrix effects and satisfactory detection performance were confirmed by in-parallel LC-MS/MS analysis in different vegetable varieties at various spiked levels of 10(-3) to 10(1) mug g(-1). Overall, the testified suitability and applicability of this novel platform meet the requirements for practical use in food safety management and environmental monitoring, especially in the developing world.
ESTHER : Han_2012_Anal.Chim.Acta_720_126
PubMedSearch : Han_2012_Anal.Chim.Acta_720_126
PubMedID: 22365130

Title : A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort - Yu_2011_Behav.Brain.Funct_7_13
Author(s) : Yu J , He X , Yao D , Li Z , Li H , Zhao Z
Ref : Behav Brain Funct , 7 :13 , 2011
Abstract : BACKGROUND: Synaptic genes, NLGN3 and NLGN4X, two homologous members of the neuroligin family, have been supposed as predisposition loci for autism spectrum disorders (ASDs), and defects of these two genes have been identified in a small fraction of individuals with ASDs. But no such rare variant in these two genes has as yet been adequately replicated in Chinese population and no common variant has been further investigated to be associated with ASDs. METHODS: 7 known ASDs-related rare variants in NLGN3 and NLGN4X genes were screened for replication of the initial findings and 12 intronic tagging single nucleotide polymorphisms (SNPs) were genotyped for case-control association analysis in a total of 229 ASDs cases and 184 control individuals in a Chinese Han cohort, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS: We found that a common intronic variant, SNP rs4844285 in NLGN3 gene, and a specific 3-marker haplotype XA-XG-XT (rs11795613-rs4844285-rs4844286) containing this individual SNP were associated with ASDs and showed a male bias, even after correction for multiple testing (SNP allele: P = 0.048, haplotype:P = 0.032). Simultaneously, none of these 7 known rare mutation of NLGN3 and NLGN4X genes was identified, neither in our patients with ASDs nor controls, giving further evidence that these known rare variants might be not enriched in Chinese Han cohort. CONCLUSION: The present study provides initial evidence that a common variant in NLGN3 gene may play a role in the etiology of ASDs among affected males in Chinese Han population, and further supports the hypothesis that defect of synapse might involvement in the pathophysiology of ASDs.
ESTHER : Yu_2011_Behav.Brain.Funct_7_13
PubMedSearch : Yu_2011_Behav.Brain.Funct_7_13
PubMedID: 21569590

Title : Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1 - Kim_2010_Neurosci.Lett_479_292
Author(s) : Kim SJ , Zhang Z , Saha A , Sarkar C , Zhao Z , Xu Y , Mukherjee AB
Ref : Neuroscience Letters , 479 :292 , 2010
Abstract : Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking Ppt1, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL.
ESTHER : Kim_2010_Neurosci.Lett_479_292
PubMedSearch : Kim_2010_Neurosci.Lett_479_292
PubMedID: 20561933
Gene_locus related to this paper: mouse-ppt

Title : Efficient regioselective synthesis of 3'-O-crotonylfloxuridine catalysed by Pseudomonas cepacia lipase - Zhao_2009_Biotechnol.Appl.Biochem_52_45
Author(s) : Zhao Z , Zong M , Li N
Ref : Biotechnol Appl Biochem , 52 :45 , 2009
Abstract : Pseudomonas cepacia lipase-catalysed preferential acylation of the secondary hydroxy group of FUdR (floxuridine) with vinyl crotonate was carried out in spite of the presence of the primary hydroxy group, and 3'-O-crotonylfloxuridine was prepared successfully for the first time. The isomerization of the double bond of crotonate, which occurs in conventional organic synthesis, could be effectively avoided during the enzymatic acylation. The effects of some key factors such as reaction medium, initial a(w) (water activity), molar ratio of vinyl crotonate to FUdR, FUdR concentration and reaction temperature on the reaction were examined. Under the optimized reaction conditions, the initial reaction rate, substrate conversion and 3'-regioselectivity of the reaction were as high as 24 mM/h, 98% and 85% respectively.
ESTHER : Zhao_2009_Biotechnol.Appl.Biochem_52_45
PubMedSearch : Zhao_2009_Biotechnol.Appl.Biochem_52_45
PubMedID: 18373494

Title : Effect of tanshinone on the levels of nitric oxide synthase and acetylcholinesterase in the brain of Alzheimer's disease rat model - Yin_2008_Clin.Invest.Med_31_E248
Author(s) : Yin Y , Huang L , Liu Y , Huang S , Zhuang J , Chen X , Zhang L , Wu H , Shao F , Zhao Z
Ref : Clinical Investigation Med , 31 :E248 , 2008
Abstract : PURPOSE: To determine the influence of tanshinone on the levels of nitric oxide synthase (NOS) and acetylcholinesterase (AChE) in the brain of an Alzheimer's Disease (AD) rat model and on its potential therapeutic mechanism. METHODS: 100 Male Sprague Dawley rats were divided into three groups: control group, model group and tanshinone treatment group. 10 microg A beta 1-42 was injected bilaterally into the dorsal lateral region of the dentate gyrus in the hippocampus of rats in the model and tanshinone treatment groups to prepare the AD models. 24h after modeling, tanshinone, 50mg/kg, was administered by gastric perfusion to rats in the tanshinone treatment group. Later, immunohistochemical assay and Western blot analysis were used to detect expression of neuronal NOS (nNOS) and inducible NOS (iNOS) in the rat hippocampus. Activity of AChE in each subregion (CA1 approximately CA4) of rats' hippocampus was determined by a histochemical technique. RESULTS: Expression of nNOS in the model group was down-regulated whereas iNOS was up-regulated. After A beta 1-42 injection, the number of AChE positive fibers in each subregion (CA1 approximately CA4) of the hippocampus was decreased compared with controls. With tanshinone administration, the changes were improved to varying degrees. CONCLUSION: Tanshinone modulates AChE and NOS proteins concentrations in the hippocampus of AD rats. This may have therapeutic potential in AD rats.
ESTHER : Yin_2008_Clin.Invest.Med_31_E248
PubMedSearch : Yin_2008_Clin.Invest.Med_31_E248
PubMedID: 18980714

Title : (3R,4S)-4-(2,4,5-Trifluorophenyl)-pyrrolidin-3-ylamine inhibitors of dipeptidyl peptidase IV: synthesis, in vitro, in vivo, and X-ray crystallographic characterization - Wright_2007_Bioorg.Med.Chem.Lett_17_5638
Author(s) : Wright SW , Ammirati MJ , Andrews KM , Brodeur AM , Danley DE , Doran SD , Lillquist JS , Liu S , McClure LD , McPherson RK , Olson TV , Orena SJ , Parker JC , Rocke BN , Soeller WC , Soglia CB , Treadway JL , VanVolkenburg MA , Zhao Z , Cox ED
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :5638 , 2007
Abstract : A series of pyrrolidine based inhibitors of dipeptidyl peptidase IV were developed from a high throughput screening hit for the treatment of type 2 diabetes. Potency, selectivity, and pharmacokinetic properties were optimized resulting in the identification of a pre-clinical candidate for further profiling.
ESTHER : Wright_2007_Bioorg.Med.Chem.Lett_17_5638
PubMedSearch : Wright_2007_Bioorg.Med.Chem.Lett_17_5638
PubMedID: 17822893
Gene_locus related to this paper: human-DPP4

Title : A new transgenic mouse model for the study of cell cycle control in megakaryocytes - Thompson_1996_Stem.Cells_14 Suppl 1_181
Author(s) : Thompson A , Zhao Z , Ladd D , Zimmet J , Ravid K
Ref : Stem Cells , 14 Suppl 1 :181 , 1996
Abstract : During the development of the megakaryocytic lineage, the megakaryoblasts give rise to megakaryocytes which undergo repeated S phases in the absence of cytokinesis (endomitosis). The cellular oncogene myc plays a central role in the proliferation and differentiation of several cell types. In a previous study, we generated transgenic mice carrying c-myc fused to the estrogen receptor under the control of the platelet factor four (PF4) megakaryocyte-specific promoter. The bone marrow of female transgenic mice, but not of male mice, displayed increased megakaryopoiesis. Here we report that beta-estradiol-induced activation of c-myc in cultured bone marrow cells derived from male or female transgenic mice resulted in prolonged survival of the cells in vitro. Addition of a cocktail of hemopoietic growth factors to beta-estradiol-treated cells, including interleukin 6 (IL-6), IL-3 and stem cell factor further improved the survival time in culture and increased the percentage of large mature cells, but did not result in immortalization. The majority of these PF4-expressing cells, however, did not reach the differentiation stage at which acetylcholinesterase is expressed and did not appear as large megakaryocytes. We conclude that cultured megakaryocytes overexpressing myc are induced to proliferate, but have a limited potential to fully differentiate. Under these conditions, cyclin D3 was downregulated while the level of cyclin A was slightly upregulated.
ESTHER : Thompson_1996_Stem.Cells_14 Suppl 1_181
PubMedSearch : Thompson_1996_Stem.Cells_14 Suppl 1_181
PubMedID: 11012219