Jia X

References (19)

Title : Degradation of poly(butylene adipate-co-terephthalate) films by Thermobifida fusca FXJ-1 isolated from compost - Jia_2023_J.Hazard.Mater_441_129958
Author(s) : Jia X , Zhao K , Zhao J , Lin C , Zhang H , Chen L , Chen J , Fang Y
Ref : J Hazard Mater , 441 :129958 , 2023
Abstract : In recent years, Poly(butylene adipate-co-terephthalate) (PBAT) films were wildly used due to its biodegradable properties. However, there are few reports of strains that can high efficiently degrade PBAT. Thermobifida fusca FXJ-1, a thermophilic actinomycete, was screened and identified from compost. FXJ-1 can efficiently degrade PBAT at 55C in MSM medium. The degradation rates of the pure PBAT film (PF), PBAT film used for mulching on agricultural fields (PAF), and PBAT-PLA-ST film (PPSF) were 82.871.01%, 87.832.00% and 52.530.54%, respectively, after nine days of incubation in MSM medium. Cracking areas were monitored uniformly distributed on the surfaces of three kinds of PBAT-based films after treatment with FXJ-1 using scanning electron microscopy. The LC-MS results showed that PBAT might be degraded into adipic acid, terephthalic acid, butylene adipate, butylene terephthalate and butylene adipate-co-terephthalate, and these products are involved in the cleavage of ester bonds. We also found that amylase produced by FXJ-1 played an important role in the degradation of PPSF. FXJ-1 also showed an efficient PBAT-based films degradation ability in simulating compost environment, which implied its potential application in PBAT and starch-based film degradation by industrial composting.
ESTHER : Jia_2023_J.Hazard.Mater_441_129958
PubMedSearch : Jia_2023_J.Hazard.Mater_441_129958
PubMedID: 36122523

Title : Research Mechanism and Progress of the Natural Compound Curcumin in Treating Alzheimers Disease - Li_2023_Mini.Rev.Med.Chem__
Author(s) : Li L , Wang F , Jia X , Yao L , Liu Y
Ref : Mini Rev Med Chem , : , 2023
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. AD patients usually present symptoms, such as cognitive dysfunction, progressive memory loss, and other manifestations. With the increasing number of AD cases worldwide, there is an urgent need to develop effective drug treatments. Currently, drugs targeting AD symptoms may not change or prevent the progression of the disease. Curcumin, a polyphenol extracted from the turmeric herb, has been used for the treatment of AD. In this review, we summarized both cellular and animal studies and described the mechanism of action of curcumin in altering the pathological features of AD. Curcumin attenuates the formation of amyloid-beta plaques and promotes its decomposition, reduces the phosphorylation of tau, improves its clearance rate, and binds with copper to reduce cholesterol. It changes the activity of microglia, suppresses acetylcholinesterase, regulates insulin signal transduction, and exhibits antioxidant properties. Studies have found that curcumin can promote nerve repair and has a significant effect on AD. However, the low bioavailability of curcumin may hinder its use as a therapeutic agent. If this limitation can be overcome, curcumin may emerge as a promising drug for the treatment of AD.
ESTHER : Li_2023_Mini.Rev.Med.Chem__
PubMedSearch : Li_2023_Mini.Rev.Med.Chem__
PubMedID: 37929738

Title : The Relationship between Intracarotid Plaque Neovascularization and Lp (a) and Lp-PLA2 in Elderly Patients with Carotid Plaque Stenosis - Sun_2022_Dis.Markers_2022_6154675
Author(s) : Sun C , Xi N , Sun Z , Zhang X , Wang X , Cao H , Jia X
Ref : Dis Markers , 2022 :6154675 , 2022
Abstract : The aim of this study was to investigate the relationship between carotid plaque neovascularization and lipoprotein (a) [Lp (a)], lipoprotein-associated phospholipase A2 (Lp-PLA2) in elderly patients with carotid plaque stenosis. One hundred elderly patients with carotid plaque stenosis diagnosed in our hospital from January 2020 to January 2022 were retrospectively analyzed and divided into stable (n = 62) and unstable (n = 38) groups according to whether the plaque was stable or not. Plasma Lp (a), Lp-PLA2, apoA, and apoB levels were measured; intraplaque angiogenesis (IPN) scores were examined by contrast-enhanced ultrasound (CEUS) to assess IPN grade in patients; and Pearson correlation was used to analyze the relationship between plasma Lp (a) and Lp-PLA2 levels and plaque characteristics and angiogenesis. The maximum thickness and total thickness of carotid plaque in the unstable group were significantly greater than those in the stable group (P < 0.05); the IPN grade was mainly grade III and IV in the unstable group and grade II in the stable group, and the IPN score was significantly higher in the unstable group than in the stable group (P < 0.05); there was no significant difference in the plasma apoA and apoB levels between the two groups (P > 0.05), and the plasma Lp (a) and Lp-PLA2 levels were significantly higher in the unstable group than in the stable group (P < 0.05); the neovascular grade, plasma Lp-PLA2, and Lp (a) levels were significantly increased (P < 0.05); the plasma Lp (a) and Lp-PLA2 levels were positively correlated with the maximum plaque thickness, total plaque thickness, degree of stenosis, and angiogenesis (P < 0.05). The plasma levels of Lp (a) and Lp-PLA2 are positively correlated with intraplaque angiogenesis, and their levels can reflect the stability of carotid plaques.
ESTHER : Sun_2022_Dis.Markers_2022_6154675
PubMedSearch : Sun_2022_Dis.Markers_2022_6154675
PubMedID: 35493296

Title : Antioxidant, Antibacterial, Enzyme Inhibitory, and Anticancer Activities and Chemical Composition of Alpinia galanga Flower Essential Oil - Tian_2022_Pharmaceuticals.(Basel)_15_
Author(s) : Tian Y , Jia X , Wang Q , Lu T , Deng G , Tian M , Zhou Y
Ref : Pharmaceuticals (Basel) , 15 : , 2022
Abstract : Alpinia galanga is widely cultivated for its essential oil (EO), which has been used in cosmetics and perfumes. Previous studies of A. galanga focussed mostly on the rhizome but seldom on the flower. Therefore, this study was designed to identify the chemical composition of A. galanga flower EO and firstly estimate its antioxidant, antibacterial, enzyme inhibitory, and anticancer activities. According to the results of the gas chromatography with flame ionization or mass selective detection (GC-FID/MS) analysis, the most abundant component of the EO was farnesene (64.3%), followed by farnesyl acetate (3.6%), aceteugenol (3.2%), eugenol (3.1%), E-nerolidol (2.9%), decyl acetate (2.4%), octyl acetate (2.0%), sesquirosefuran (1.9%), (E)-beta-farnesene (1.7%), and germacrene D (1.5%). For the bioactivities, the EO exhibited moderate DPPH and ABTS radical scavenging effects with IC(50) values of 138.62 +/- 3.07 microg/mL and 40.48 +/- 0.49 microg/mL, respectively. Moreover, the EO showed strong-to-moderate antibacterial activities with various diameter of inhibition zone (DIZ) (8.79-14.32 mm), minimal inhibitory concentration (MIC) (3.13-6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25-12.50 mg/mL) values against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris. Interestingly, the EO possessed remarkable alpha-glucosidase inhibition (IC(50) = 0.16 +/- 0.03 mg/mL), which was equivalent to that of the positive control acarbose (IC(50) = 0.15 +/- 0.01 mg/mL) (p > 0.05). It showed moderate tyrosinase inhibition (IC(50) = 0.62 +/- 0.09 mg/mL) and weak inhibitory activity on acetylcholinesterase (AChE) (IC(50) = 2.49 +/- 0.24 mg/mL) and butyrylcholinesterase (BChE) (IC(50) = 10.14 +/- 0.59 mg/mL). Furthermore, the EO exhibited considerable selective cytotoxicity to K562 cells (IC(50) = 41.55 +/- 2.28 microg/mL) and lower cytotoxicity to non-cancerous L929 cells (IC(50) = 120.54 +/- 8.37 microg/mL), and it induced K562 cell apoptosis in a dose-dependent manner. Hence, A. galanga flower EO could be regarded as a bioactive natural product with great application potential in the pharmaceutical field.
ESTHER : Tian_2022_Pharmaceuticals.(Basel)_15_
PubMedSearch : Tian_2022_Pharmaceuticals.(Basel)_15_
PubMedID: 36145290

Title : Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target - Xu_2022_PLoS.Pathog_18_e1010615
Author(s) : Xu Y , Yang J , Li W , Song S , Shi Y , Wu L , Sun J , Hou M , Wang J , Jia X , Zhang H , Huang M , Lu T , Gan J , Feng Y
Ref : PLoS Pathog , 18 :e1010615 , 2022
Abstract : Tuberculosis (TB) is one of the leading infectious diseases of global concern, and one quarter of the world's population are TB carriers. Biotin metabolism appears to be an attractive anti-TB drug target. However, the first-stage of mycobacterial biotin synthesis is fragmentarily understood. Here we report that three evolutionarily-distinct BioH isoenzymes (BioH1 to BioH3) are programmed in biotin synthesis of Mycobacterium smegmatis. Expression of an individual bioH isoform is sufficient to allow the growth of an Escherichia coli deltabioH mutant on the non-permissive condition lacking biotin. The enzymatic activity in vitro combined with biotin bioassay in vivo reveals that BioH2 and BioH3 are capable of removing methyl moiety from pimeloyl-ACP methyl ester to give pimeloyl-ACP, a cognate precursor for biotin synthesis. In particular, we determine the crystal structure of dimeric BioH3 at 2.27A, featuring a unique lid domain. Apart from its catalytic triad, we also dissect the substrate recognition of BioH3 by pimeloyl-ACP methyl ester. The removal of triple bioH isoforms (deltabioH1/2/3) renders M. smegmatis biotin auxotrophic. Along with the newly-identified Tam/BioC, the discovery of three unusual BioH isoforms defines an atypical 'BioC-BioH(3)' paradigm for the first-stage of mycobacterial biotin synthesis. This study solves a long-standing puzzle in mycobacterial nutritional immunity, providing an alternative anti-TB drug target.
ESTHER : Xu_2022_PLoS.Pathog_18_e1010615
PubMedSearch : Xu_2022_PLoS.Pathog_18_e1010615
PubMedID: 35816546
Gene_locus related to this paper: mycs2-a0r6y0

Title : Background-free sensing platform for on-site detection of carbamate pesticide through upconversion nanoparticles-based hydrogel suit - Su_2021_Biosens.Bioelectron_194_113598
Author(s) : Su D , Zhao X , Yan X , Han X , Zhu Z , Wang C , Jia X , Liu F , Sun P , Liu X , Lu G
Ref : Biosensors & Bioelectronics , 194 :113598 , 2021
Abstract : On-site monitoring of carbamate pesticide in complex matrix remians as a challenge in terms of the real-time control of food safety and supervision of environmental quality. Herein, we fabricated robust upconversion nanoparticles (UCNPS)/polydopamine (PDA)-based hydrogel portable suit that precisely quantified carbaryl in complex tea samples with smartphone detector. UCNPS/PDA nanoprobe was developed by polymerization of dopamine monomers on the surface of NaErF(4): 0.5% Tm(3+)@NaYF(4) through electrostatic interaction, leading to efficient red luminescence quenching of UCNPS under near-infrared excitation, which circumvented autofluorescence and background interference in complicated environment. Such a luminescence quenching could be suppressed by thiocholine that was produced by acetylcholinesterase-mediated catalytic reaction, thus enabling carbaryl bioassay by inhibiting the activity of enzyme. Bestowed with the feasibility analysis of fluorescent output, portable platform was designed by integrating UCNPS-embedded sodium alginate hydrogel with 3D-printed smartphone device for quantitatively on-site monitoring of carbaryl in the range of 0.5-200 ng mL(-1) in tea sample, accompanied by a detection limit of 0.5 ng mL(-1). Owing to specific UCNPS signatures and hydrogel immobilization, this modular platform displayed sensitive response, portability and anti-interference capability in complex matrix analysis, thus holding great potential in point-of-care application.
ESTHER : Su_2021_Biosens.Bioelectron_194_113598
PubMedSearch : Su_2021_Biosens.Bioelectron_194_113598
PubMedID: 34507097

Title : A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF(4): 0.5 \% Ho(3+)@NaYF(4) upconversion nano-probe - Zhao_2021_Talanta_235_122784
Author(s) : Zhao X , Zhang L , Yan X , Lu Y , Pan J , Zhang M , Wang C , Suo H , Jia X , Liu X , Lu G
Ref : Talanta , 235 :122784 , 2021
Abstract : Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF(4): 0.5 % Ho(3+)@NaYF(4) nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL(-) (1) for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL(-1), indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease.
ESTHER : Zhao_2021_Talanta_235_122784
PubMedSearch : Zhao_2021_Talanta_235_122784
PubMedID: 34517642

Title : Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties - Zhang_2020_Nat.Commun_11_3719
Author(s) : Zhang W , Zhang Y , Qiu H , Guo Y , Wan H , Zhang X , Scossa F , Alseekh S , Zhang Q , Wang P , Xu L , Schmidt MH , Jia X , Li D , Zhu A , Guo F , Chen W , Ni D , Usadel B , Fernie AR , Wen W
Ref : Nat Commun , 11 :3719 , 2020
Abstract : Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds.
ESTHER : Zhang_2020_Nat.Commun_11_3719
PubMedSearch : Zhang_2020_Nat.Commun_11_3719
PubMedID: 32709943
Gene_locus related to this paper: camsi-a0a7j7g2i2 , camsi-a0a7j7hil4

Title : Structural Insights into the Dual-Substrate Recognition and Catalytic Mechanisms of a Bifunctional Acetyl Ester-Xyloside Hydrolase from Caldicellulosiruptor lactoaceticus - Cao_2019_ACS.Catal_9_1739
Author(s) : Cao H , Sun L , Huang Y , Liu X , Yang D , Liu T , Jia X , Wen B , Gu T , Wang F , Xin F
Ref : ACS Catal , 9 :1739 , 2019
Abstract : Enzymes are usually characterized by their evolutionarily conserved catalytic domains; however, this work presents the incidental gain-of-function of an enzyme in a loop region by natural evolution of its amino acids. A bifunctional acetyl ester-xyloside hydrolase (CLH10) was heterologously expressed, purified, and characterized. The primary sequence of CLH10 contains the fragments of the conserved sequence of esterase and glycosidase, which distribute in a mixed type. The crystal structure revealed that the primary sequence folded into two independent structural regions to undertake both acetyl esterase and beta-1,4-xylanase hydrolase functions. CLH10 is capable of cleaving both the beta-1,4-xylosidic bond-linked main chain and the ester bond-linked acetylated side chain of xylan, which renders it valuable because it can degrade acetylated xylan within one enzyme. Significantly, the beta-1,4-xylanase activity of CLH10 appears to have been fortuitously obtained because of the variable Asp10 and Glu139 located in its loop region, which suggested that the exposed loop region might act as a potential hot-spot for the design and generation of promising enzyme function in both directed evolution and rational protein design.
ESTHER : Cao_2019_ACS.Catal_9_1739
PubMedSearch : Cao_2019_ACS.Catal_9_1739
Gene_locus related to this paper: 9firm-g2pvg6

Title : Transfection of neurotrophin-3 into neural stem cells using ultrasound with microbubbles to treat denervated muscle atrophy - Gong_2018_Exp.Ther.Med_15_620
Author(s) : Gong L , Jiang C , Liu L , Wan S , Tan W , Ma S , Jia X , Wang M , Hu A , Shi Y , Zhang Y , Shen Y , Wang F , Chen Y
Ref : Exp Ther Med , 15 :620 , 2018
Abstract : Neurotrophin-3 (NT-3) has potential as a therapeutic agent for the treatment of patients with denervated muscle atrophy. However, the endogenous secretion of NT-3 is low and exogenous NT-3 lacks sufficient time to accumulate due to its short half-life. The transfection of NT-3 has been demonstrated to have a beneficial effect on denervated muscle and motor endplates. Neural stem cells (NSCs) differentiate into neurons and form motor endplate nerve-muscle connections. It has been previously demonstrated that local and noninvasive transfection can be performed using ultrasound with microbubbles (MBs). In the current study, hematoxylin and eosin, acetylcholinesterase and gold chloride staining, as well as transmission electron microscopy, were performed to verify the effects of this treatment strategy. The results demonstrated that using ultrasound with MBs for the transfection of NT-3 into NSCs, and their subsequent transplantation in vivo, attenuated the atrophy of denervated muscle and reduced motor endplate degeneration. This noninvasive, efficient and targeted treatment strategy may therefore be a potential treatment for patients with denervated muscle atrophy.
ESTHER : Gong_2018_Exp.Ther.Med_15_620
PubMedSearch : Gong_2018_Exp.Ther.Med_15_620
PubMedID: 29403547

Title : Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4 - Wei_2018_Appl.Environ.Microbiol_84_
Author(s) : Wei Y , Fu J , Wu J , Jia X , Zhou Y , Li C , Dong M , Wang S , Zhang J , Chen F
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.
ESTHER : Wei_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Wei_2018_Appl.Environ.Microbiol_84_
PubMedID: 29079625

Title : The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice - Jia_2017_Nanoscale.Res.Lett_12_478
Author(s) : Jia X , Wang S , Zhou L , Sun L
Ref : Nanoscale Res Lett , 12 :478 , 2017
Abstract : Nanoscale titanium dioxide (nano-TiO2) has been widely used in industry and medicine. However, the safety of nano-TiO2 exposure remains unclear. In this study, we evaluated the liver, brain, and embryo toxicity and the underlying mechanism of nano-TiO2 using mice models. The results showed that titanium was distributed to and accumulated in the heart, brain, spleen, lung, and kidney of mice after intraperitoneal (i.p.) nano-TiO2 exposure, in a dose-dependent manner. The organ/body weight ratios of the heart, spleen, and kidney were significantly increased, and those of the brain and lung were decreased. High doses of nano-TiO2 significantly damaged the functions of liver and kidney and glucose and lipid metabolism, as showed in the blood biochemistry tests. Nano-TiO2 caused damages in mitochondria and apoptosis of hepatocytes, generation of reactive oxygen species, and expression disorders of protective genes in the liver of mice. We found ruptured and cracked nerve cells and inflammatory cell infiltration in the brain. We also found that the activities of constitutive nitric oxide synthases (cNOS), inducible NOS (iNOS), and acetylcholinesterase, and the levels of nitrous oxide and glutamic acid were changed in the brain after nano-TiO2 exposure. Ex vivo mouse embryo models exhibited developmental and genetic toxicity after high doses of nano-TiO2. The size of nano-TiO2 particles may affect toxicity, larger particles producing higher toxicity. In summary, nano-TiO2 exhibited toxicity in multiple organs in mice after exposure through i.p. injection and gavage. Our study may provide data for the assessment of the risk of nano-TiO2 exposure on human health.
ESTHER : Jia_2017_Nanoscale.Res.Lett_12_478
PubMedSearch : Jia_2017_Nanoscale.Res.Lett_12_478
PubMedID: 28774157

Title : Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats - Wang_2017_Mol.Med.Rep_16_3233
Author(s) : Wang F , Wu Z , Zha X , Cai Y , Wu B , Jia X , Zhu D
Ref : Mol Med Rep , 16 :3233 , 2017
Abstract : The aim of the present study was to observe the effects of the concurrent administration of thyroxine (T4) and an acetylcholinesterase (AChE) inhibitor, donepezil (DON), on the hypothyroidisminduced ultrastructural changes of the prefrontal cortex (PFC) in adult rats. The acetylcholine (ACh) content and AChE activity was assessed, as well as the expressions of synaptotagmin1 (syt1) and SNAP25 were analyzed in the rats. Adding 0.05% propylthiouracil to rats' drinking water induced a hypothyroid rat model. The animals were treated with T4 and DON administered separately or in combination from the fifth week. Transmission electron microscope analysis revealed that hypothyroidism induced marked ultrastructural changes, including the neurons, the synapses and the myelin sheath in the PFC. T4 or DON treatment improved the morphologic features of the PFC, and the performance of the T4 combined DON group was the closest to the control group. Moreover, hypothyroidism significantly decreased the content of ACh (29.8%) and activity of AChE (27.8%), which were restored to control values by T4 admi-nistration. In addition, DON treatment restored ACh content to normal. At the protein level, hypothyroidism increased the levels of syt1 and SNAP25 in the PFC, both of which were not restored to control values following T4 administration, while concurrent administration of T4 and DON was able to induce this effect. These results suggested that adultonset hypothyroidism induce morphological, biochemical and molecular alterations in the PFC, combined administration of T4 and DON induce plastic changes in the PFC, different from that of the standard T4 therapy, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
ESTHER : Wang_2017_Mol.Med.Rep_16_3233
PubMedSearch : Wang_2017_Mol.Med.Rep_16_3233
PubMedID: 28713915

Title : Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats - Wang_2015_Mol.Med.Rep_11_775
Author(s) : Wang F , Zeng X , Zhu Y , Ning D , Liu J , Liu C , Jia X , Zhu D
Ref : Mol Med Rep , 11 :775 , 2015
Abstract : A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a signi fi cant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
ESTHER : Wang_2015_Mol.Med.Rep_11_775
PubMedSearch : Wang_2015_Mol.Med.Rep_11_775
PubMedID: 25371181

Title : Effects of thyroxin and donepezil on hippocampal acetylcholine content and syntaxin-1 and munc-18 expression in adult rats with hypothyroidism - Wang_2014_Exp.Ther.Med_7_529
Author(s) : Wang N , Cai Y , Wang F , Zeng X , Jia X , Tao F , Zhu D
Ref : Exp Ther Med , 7 :529 , 2014
Abstract : Adult-onset hypothyroidism induces various impairments in hippocampus-dependent cognitive function, in which numerous synaptic proteins and neurotransmitters are involved. Donepezil (DON), an acetylcholinesterase inhibitor, has been shown to be efficient in improving cognitive function. The aim of the present study was to investigate the effects of adult-onset hypothyroidism on the expression levels of the synaptic proteins syntaxin-1 and munc-18, as well as the content of the neurotransmitter acetylcholine (ACh) in the hippocampus. In addition, the study explored the effects of thyroxin (T4) and DON treatment on the altered parameters. The study involved 55 Sprague-Dawley rats that were randomly divided into five groups: Control, hypothyroid (0.05% 6-n-propyl-2-thiouracil; added to the drinking water), hypothyroid treated with T4 (6 mug/100 g body weight once daily; intraperitoneal injection), hypothyroid treated with DON (0.005%; added to the drinking water) and hypothyroid treated with a combination of the two drugs (6 mug/100 g T4 and 0.005% DON). The concentration of ACh was determined in the homogenized hippocampus of each animal by alkaline hydroxylamine colorimetry. The protein levels of syntaxin-1 and munc-18 were determined by immunohistochemistry. The results showed that the content of ACh in the hippocampi of the hypothyroid rats was significantly decreased compared with that in the controls and that T4 monotherapy and DON administration restored the ACh content to normal values. In the hippocampi of the hypothyroid group, munc-18 was expressed at significantly lower levels, while the expression levels of syntaxin-1 were increased compared with the levels in the control group. Treatment with T4 alone restored the expression of syntaxin-1 but failed to normalize munc-18 expression levels. The co-administration of T4 and DON returned the munc-18 levels to normal values. These observations indicate that adult-onset hypothyroidism induces alterations in the levels of munc-18, syntaxin-1 and ACh in the hippocampus. Syntaxin-1 and ACh levels were restored by T4 monotherapy while munc-18 levels were not. In addition, the co-administration of T4 and DON resulted in more effective restoration than either alone. The thyroid hormone has a direct effect on metabolism of hippocampal ACh in adult rats and DON is helpful for treatment of synaptic protein impairment induced by hypothyroidism.
ESTHER : Wang_2014_Exp.Ther.Med_7_529
PubMedSearch : Wang_2014_Exp.Ther.Med_7_529
PubMedID: 24520241

Title : New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol - Mao_2014_Org.Biomol.Chem_12_5936
Author(s) : Mao F , Yan J , Li J , Jia X , Miao H , Sun Y , Huang L , Li X
Ref : Org Biomol Chem , 12 :5936 , 2014
Abstract : Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the 'multi-target-directed ligands' (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced beta-amyloid (Abeta) aggregation and copper(II)-induced Abeta aggregation, potential antioxidant behaviour (ORAC-FL value of 0.9-3.2 Trolox equivalents) and biometal chelation. Among these compounds, (E)-5-(4-hydroxystyryl)quinoline-8-ol (10c) showed the most potent ability to inhibit self-induced Abeta aggregation (IC50 = 8.50 microM) and copper(II)-induced Abeta aggregation and to disassemble the well-structured Abeta fibrils generated by self- and copper(II)-induced Abeta aggregation. Note that 10c could also control Cu(I/II)-triggered hydroxyl radical (OH) production by halting copper redox cycling via metal complexation, as confirmed by a Cu-ascorbate redox system assay. Importantly, 10c did not show acute toxicity in mice at doses of up to 2000 mg kg1 and was able to cross the blood-brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicate that compound 10c is a promising multifunctional compound for the development of novel drugs for AD.
ESTHER : Mao_2014_Org.Biomol.Chem_12_5936
PubMedSearch : Mao_2014_Org.Biomol.Chem_12_5936
PubMedID: 24986600

Title : Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses - Chu_2014_Int.Immunopharmacol_19_317
Author(s) : Chu S , Gu J , Feng L , Liu J , Zhang M , Jia X , Liu M , Yao D
Ref : Int Immunopharmacol , 19 :317 , 2014
Abstract : Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-alpha and IL-1beta (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Abeta deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Abeta deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD.
ESTHER : Chu_2014_Int.Immunopharmacol_19_317
PubMedSearch : Chu_2014_Int.Immunopharmacol_19_317
PubMedID: 24503167

Title : SET-mediated NDRG1 inhibition is involved in acquisition of epithelial-to-mesenchymal transition phenotype and cisplatin resistance in human lung cancer cell - Liu_2014_Cell.Signal_26_2710
Author(s) : Liu H , Gu Y , Yin J , Zheng G , Wang C , Zhang Z , Deng M , Liu J , Jia X , He Z
Ref : Cell Signal , 26 :2710 , 2014
Abstract : Development of resistance to therapy continues to be a serious clinical problem in lung cancer management. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) have been shown to play roles in resistance to chemotherapy. Here, we utilized a proteomics-based method and identified a significant downregulation of the metastasis suppressor NDRG1 in drug resistant lung cancer cells. We showed that downregulation of DNRG1 constitutes a mechanism for acquisition of EMT phenotype and endows lung cancer cells with an increased resistance to cisplatin. We also identified a signal cascade, namely, SET--- PP2A---| c-myc---| NDRG1, in which upregulation of SET is critical for inhibition of NDRG1. We also found that blockade of SET (or reactivation of PP2A) by FTY720 reverted EMT, restored drug sensitivity, and inhibited invasiveness and growth of lung tumor xenografts. Together, our results indicated a functional link between SET-mediated NDRG1 regulation and acquisition of EMT phenotype and drug resistance, and provided an evidence that blockade of SET-driven EMT can overcome drug resistance and inhibit tumor progression.
ESTHER : Liu_2014_Cell.Signal_26_2710
PubMedSearch : Liu_2014_Cell.Signal_26_2710
PubMedID: 25152373

Title : Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics - Fang_2008_J.Bacteriol_190_6014
Author(s) : Fang J , Zhang Y , Huang L , Jia X , Zhang Q , Zhang X , Tang G , Liu W
Ref : Journal of Bacteriology , 190 :6014 , 2008
Abstract : Tetrocarcin A (TCA), produced by Micromonospora chalcea NRRL 11289, is a spirotetronate antibiotic with potent antitumor activity and versatile modes of action. In this study, the biosynthetic gene cluster of TCA was cloned and localized to a 108-kb contiguous DNA region. In silico sequence analysis revealed 36 putative genes that constitute this cluster (including 11 for unusual sugar biosynthesis, 13 for aglycone formation, and 4 for glycosylations) and allowed us to propose the biosynthetic pathway of TCA. The formation of D-tetronitrose, L-amicetose, and L-digitoxose may begin with D-glucose-1-phosphate, share early enzymatic steps, and branch into different pathways by competitive actions of specific enzymes. Tetronolide biosynthesis involves the incorporation of a 3-C unit with a polyketide intermediate to form the characteristic spirotetronate moiety and trans-decalin system. Further substitution of tetronolide with five deoxysugars (one being a deoxynitrosugar) was likely due to the activities of four glycosyltransferases. In vitro characterization of the first enzymatic step by utilization of 1,3-biphosphoglycerate as the substrate and in vivo cross-complementation of the bifunctional fused gene tcaD3 (with the functions of chlD3 and chlD4) to Delta chlD3 and Delta chlD4 in chlorothricin biosynthesis supported the highly conserved tetronate biosynthetic strategy in the spirotetronate family. Deletion of a large DNA fragment encoding polyketide synthases resulted in a non-TCA-producing strain, providing a clear background for the identification of novel analogs. These findings provide insights into spirotetronate biosynthesis and demonstrate that combinatorial-biosynthesis methods can be applied to the TCA biosynthetic machinery to generate structural diversity.
ESTHER : Fang_2008_J.Bacteriol_190_6014
PubMedSearch : Fang_2008_J.Bacteriol_190_6014
PubMedID: 18586939
Gene_locus related to this paper: micch-b5l6l6