Gao Z

References (40)

Title : Inhibition of soluble epoxide hydrolase as a therapeutic approach for blood-brain barrier dysfunction - Li_2024_Biochimie__
Author(s) : Li S , Song H , Sun Y , Zhang H , Gao Z
Ref : Biochimie , : , 2024
Abstract : The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases. EpFAs play a protective role in the central nervous system via preventing neuroinflammation, making sEH a potential therapeutic target for CNS diseases. Recent studies showed that sEH inhibition prevented BBB impairment caused by stroke, hemorrhage, traumatic brain injury, hyperglycemia and sepsis via regulating the expression of tight junctions. In this review, the protective actions of sEH inhibition on BBB and potential mechanisms are summarized, and some important questions that remain to be resolved are also addressed.
ESTHER : Li_2024_Biochimie__
PubMedSearch : Li_2024_Biochimie__
PubMedID: 38531484
Gene_locus related to this paper: human-EPHX2

Title : ABHD6 suppresses colorectal cancer progression via AKT signaling pathway - Xiong_2024_Mol.Carcinog__
Author(s) : Xiong X , Yang C , Jin Y , Zhang R , Wang S , Gan L , Hou S , Bao Y , Zeng Z , Ye Y , Gao Z
Ref : Mol Carcinog , : , 2024
Abstract : Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.
ESTHER : Xiong_2024_Mol.Carcinog__
PubMedSearch : Xiong_2024_Mol.Carcinog__
PubMedID: 38197491
Gene_locus related to this paper: human-ABHD6

Title : Role of Mn-LIPA in Sex Hormone Regulation and Gonadal Development in the Oriental River Prawn, Macrobrachium nipponense - Cai_2024_Int.J.Mol.Sci_25_
Author(s) : Cai P , Zhang W , Jiang S , Xiong Y , Qiao H , Yuan H , Gao Z , Zhou Y , Jin S , Fu H
Ref : Int J Mol Sci , 25 : , 2024
Abstract : This study investigates the role of lysosomal acid lipase (LIPA) in sex hormone regulation and gonadal development in Macrobrachium nipponense. The full-length Mn-LIPA cDNA was cloned, and its expression patterns were analyzed using quantitative real-time PCR (qPCR) in various tissues and developmental stages. Higher expression levels were observed in the hepatopancreas, cerebral ganglion, and testes, indicating the potential involvement of Mn-LIPA in sex differentiation and gonadal development. In situ hybridization experiments revealed strong Mn-LIPA signaling in the spermatheca and hepatopancreas, suggesting their potential role in steroid synthesis (such as cholesterol, fatty acids, cholesteryl ester, and triglycerides) and sperm maturation. Increased expression levels of male-specific genes, such as insulin-like androgenic gland hormone (IAG), sperm gelatinase (SG), and mab-3-related transcription factor (Dmrt11E), were observed after dsMn-LIPA (double-stranded LIPA) injection, and significant inhibition of sperm development and maturation was observed histologically. Additionally, the relationship between Mn-LIPA and sex-related genes (IAG, SG, and Dmrt11E) and hormones (17beta-estradiol and 17alpha-methyltestosterone) was explored by administering sex hormones to male prawns, indicating that Mn-LIPA does not directly control the production of sex hormones but rather utilizes the property of hydrolyzing triglycerides and cholesterol to provide energy while influencing the synthesis and secretion of self-sex hormones. These findings provide valuable insights into the function of Mn-LIPA in M. nipponense and its potential implications for understanding sex differentiation and gonadal development in crustaceans. It provides an important theoretical basis for the realization of a monosex culture of M. nipponense.
ESTHER : Cai_2024_Int.J.Mol.Sci_25_
PubMedSearch : Cai_2024_Int.J.Mol.Sci_25_
PubMedID: 38338678

Title : Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats - Shao_2023_J.Invest.Surg_36_1
Author(s) : Shao Y , Li C , Jiang Y , Li H , Tang X , Gao Z , Zhang D
Ref : J Invest Surg , 36 :1 , 2023
Abstract : Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown.Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI.Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-alpha, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1 and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining.Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-alpha, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats.Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.
ESTHER : Shao_2023_J.Invest.Surg_36_1
PubMedSearch : Shao_2023_J.Invest.Surg_36_1
PubMedID: 36350036

Title : Toxic effects of the heavy metal Cd on Apis cerana cerana (Hymenoptera: Apidae): Oxidative stress, immune disorders and disturbance of gut microbiota - Li_2023_Sci.Total.Environ__169318
Author(s) : Li Z , Guo D , Wang C , Chi X , Liu Z , Wang Y , Wang H , Guo X , Wang N , Xu B , Gao Z
Ref : Sci Total Environ , :169318 , 2023
Abstract : Cadmium (Cd) is a toxic non-essential metal element that can enter the honey bee body through air, water and soil. Currently, there is a lack of sufficient research on the effects of Cd on A. cerana cerana, especially the potential risks of long-term exposure to sublethal concentrations. In order to ascertain the toxicological effects of the heavy metal Cd on bees, we performed laboratory-based toxicity experiments on worker bees and conducted analyses from three distinctive facets: antioxidative, immunological, and gut microbiota. The results showed that exposure of bees to high concentrations of Cd resulted in acute mortality, and the increase in mortality was concentration dependent. In long-term exposure to sublethal concentrations, Cd reduced the number of transcripts of antioxidant genes (AccSOD1, AccTPx3 and AccTPx4) and superoxide dismutase activity, causing an increase in malondialdehyde content. Simultaneously, the transcription of immune-related genes (AccAbaecin and AccApidaecin) and acetylcholinesterase activities was inhibited. Furthermore, Cd changes the structural characteristics of bacterial and fungal communities in the gut, disrupting the balance of microbial communities. In conclusion, the health and survival of honey bees are affected by Cd. This study provides a scientific basis for investigating the toxicological mechanisms and control strategies of the heavy metal Cd on honey bees, while facilitating a better understanding and protection of these valuable honey bees.
ESTHER : Li_2023_Sci.Total.Environ__169318
PubMedSearch : Li_2023_Sci.Total.Environ__169318
PubMedID: 38143006

Title : Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors - Tian_2022_Bioorg.Chem_127_105898
Author(s) : Tian Y , Li S , Dong K , Su X , Fu S , Lv X , Duan M , Yang T , Han Y , Hu G , Liu J , Sun Y , Yue H , Zhang H , Du Z , Miao Z , Tong M , Liu Y , Qin M , Gong P , Hou Y , Gao Z , Zhao Y
Ref : Bioorg Chem , 127 :105898 , 2022
Abstract : The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC(50) value of 0.04 +/- 0.01 nM and a K(i) value of 0.2 +/- 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors.
ESTHER : Tian_2022_Bioorg.Chem_127_105898
PubMedSearch : Tian_2022_Bioorg.Chem_127_105898
PubMedID: 35792317

Title : Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors - Tian_2022_Bioorg.Med.Chem.Lett_70_128805
Author(s) : Tian Y , Li S , Yang P , Su X , Liu J , Lv X , Dong K , Yang T , Duan M , Hu G , Yue H , Sun Y , Zhang H , Du Z , Miao Z , Tong M , Hou Y , Gao Z , Zhao Y
Ref : Bioorganic & Medicinal Chemistry Lett , 70 :128805 , 2022
Abstract : The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC(50) value of 0.03 +/- 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.
ESTHER : Tian_2022_Bioorg.Med.Chem.Lett_70_128805
PubMedSearch : Tian_2022_Bioorg.Med.Chem.Lett_70_128805
PubMedID: 35598794

Title : Improved Aitongxiao prescription (I-ATXP) induces apoptosis, cell cycle arrest and blocks exosomes release in hepatocellular carcinoma (HCC) cells - Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
Author(s) : Huang MB , Gao Z , Xia M , Zhao X , Fan X , Lin S , Zhang L , Huang L , Wei A , Zhou H , Wu JY , Roth WW , Bond VC , Leng J
Ref : Int Journal de Physiologie Pathophysiol Pharmacol , 14 :90 , 2022
Abstract : BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy globally, after lung cancer, accounting for 85-90% of primary liver cancer. Hepatitis B virus (HBV) infection is considered the leading risk factor for HCC development in China. HCC is a highly malignant cancer whose metastasis is primarily influenced by the tumor microenvironment. The role of exosomes in cancer development has become the focus of much research due to the many newly described contents of exosomes, which may contribute to tumorigenesis. However, the possible role exosomes play in the interactions between HCC cells and their surrounding hepatic milieu is mainly unknown. We discovered an Improved Aitongxiao Prescription (I-ATXP): an 80% alcohol extract from a mix of 15 specific plant and animal compounds, which had been shown to have an anticancer effect through inducing apoptosis and cell cycle arrest and blocking exosomes release in HCC cells. However, the anticancer mechanism of I-ATXP on human liver carcinoma is still unclear. OBJECTIVE: Due to its inhibitory effects on chemical carcinogenesis and inflammation, I-ATXP has been proposed as an effective agent for preventing or treating human liver carcinoma. In this study, we aimed to explore the effect of I-ATXP on proliferation, apoptosis, and cell cycles of different HCC cell lines. We investigated the impact of I-ATXP on exosomes' secretion derived from these HCC cells. METHODS: The inhibitory effect of I-ATXP on proliferation and cytotoxicity of HepG2, SMMC7721, HKCL-C3 HCC cell lines, and MIHA immortalized hepatocyte cell line was assessed by CCK-8 assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry using Annexin V-FITC/PI staining. The expression of Alix and CD63 of exosome marker proteins was detected by western blotting. The exosome protein concentration was measured by a fluorescent plate reader. The exosome-specific enzyme activity was measured by acetylcholinesterase (AchE) assay, and exosome morphological characteristics were identified by transmission electron microscopy (TEM). RESULTS: I-ATXP inhibited the growth of HCC cells in a dose and time-dependent manner. Flow cytometry analysis showed that I-ATXP induced G0/G1 phase arrest and cell apoptosis. The I-ATX reduced HepG2, SMMC7721, and HKCI-C HCC cell lines exosomes release and low-dose I-ATXP significantly enhanced the growth inhibition induced by 5-Fu. Western blot analysis shows that after HCC cell lines were treated with various concentrations of I-ATXP (0.125-1 mg/ml) for 24 h, exosomes derived from three different HCC cells expressed exosome-specific proteins Alix and CD63. Compared with the untreated group, with the increment of the concentration of I-ATXP, the expression of exosome-specific proteins Alix and CD63 were reduced. These results suggest that I-ATXP can inhibit the release of exosomes with Alix and CD63 protein from HCC cells. CONCLUSIONS: I-ATXP is a traditional Chinese medicine that acts as an effective agent for preventing or treating human liver carcinoma. (i) I-ATXP can effectively inhibit cell proliferation of different HCC cells in a time and dose-dependent manner. Compared with 5-Fu, I-ATXP exhibited more selective proliferation inhibition in HCC cells, displaying traditional Chinese medicine advantages on tumor therapy and providing the experimental basis for I-ATXP clinical application. (ii) I-ATXP can induce apoptosis and cell cycle arrest in HCC cells. The CCK-8 assay results indicated that I-ATXP could inhibit HCC cell proliferation mediated by apoptosis and cell cycle arrest. (iii) I-ATXP can inhibit both the exosome releases and expression of CD63, and Alix derived from HCC cells, but the exosomes derived from liver cancer cells affect liver cancer cells' biological properties such as proliferation, invasion, and migration. These suggest that I-ATXP may affect HCC cells via regulation of exosomes of HCC cells, further indicating the potential clinical values of I-ATXP for the prevention or treatment of human liver carcinoma.
ESTHER : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedSearch : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedID: 35619665

Title : Chemical composition of essential oils from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare and their acaricidal effects on Haemaphysalis longicornis (Acari: Ixodidae) - Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
Author(s) : Qiao Y , Yu Z , Bai L , Li H , Zhang S , Liu J , Gao Z , Yang X
Ref : Ecotoxicology & Environmental Safety , 224 :112672 , 2021
Abstract : Chemical acaricides are mainly used in traditional tick control, which leads to the emergence of tick resistance and concurrently results in environmental pollution. In the present study, the chemical constituents of essential oils (EOs) from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare was analyzed, and their potential application was evaluated to control the vector tick Haemaphysalis longicornis, which is widely distributed over vast areas of Eurasia, Australia, and New Zealand. Gas chromatography-mass spectrometry analysis revealed that the phenols thymol and carvacrol accounted for 34.66% and 75.72% of the EOs of T. mongolicus and O. vulgare, respectively, whereas trans-cinnamaldehyde (49.42%) was the main constituent of C. verum EO. Immersion tests showed that the EOs of C. verum and O. vulgare had significant acaricidal activity against larval H. longicornis, with the 50% lethal concentration (LC(50)) being 16.07 and 18.02 mg/mL, respectively, and the 95% lethal concentration (LC(95)) being 120.37 and 130.09 mg/mL, respectively. The EOs of O. vulgare and T. mongolicus showed significant acaricidal activity against unfed adult H. longicornis, with LC(50) being 43.50 and 44.21 mg/mL, respectively, and LC(95) being 113.66 and 137.99 mg/mL, respectively. The fumigant toxicity test showed significant acaricidal activity of the three EOs against both unfed and engorged nymphal and adult H. longicornis. Enzyme assays revealed that the EOs of both C. verum and O. vulgare significantly inhibited glutathione S-transferase activity (P < 0.05). In contrast, the activities of carboxylesterase and multifunction oxidases were significantly inhibited by EOs extracted from all three plants (P < 0.05). Taken together, these findings suggest that plant EOs may serve as an environment-friendly alternative for synthetic acaricides in future tick control.
ESTHER : Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
PubMedSearch : Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
PubMedID: 34416637

Title : Construction of Peroxidase-like Metal-Organic Frameworks in TiO(2) Nanochannels: Robust Free-Standing Membranes for Diverse Target Sensing - Xu_2021_Anal.Chem__
Author(s) : Xu H , Guo J , Yang L , Gao Z , Song YY
Ref : Analytical Chemistry , : , 2021
Abstract : The high cost and easy denaturation of natural enzymes under environmental conditions hinder their practical usefulness in sensing devices. In this study, peroxidase (POD)-like metal-organic frameworks (MOFs) were in situ grown in the nanochannels of an anodized TiO(2) membrane (TiO(2)NM) as an electrochemical platform for multitarget sensing. By directly using a nanochannel wall as the precursor of metal nodes, Ti-MOFs were in situ derived on the nanochannel wall. Benefitting from the presence of bipyridine groups on the ligands, the MOFs in the nanochannels provide plenty of sites for Fe(3+) anchoring, thus endowing the resulting membrane (named as Fe(3+):MOFs/TiO(2)NM) with remarkable POD-like activity. Such Fe(3+)-induced POD-like activity is very sensitive to thiol-containing molecules owing to the strong coordination effect of thiols on Fe(3+). Most importantly, the POD-like activity of nanochannels can be in situ characterized by the current-potential (I-V) properties via catalyzing the oxidation of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) substrate to the corresponding positively charged product ABTS(+). As a proof-of-concept application, the free-standing POD-like membranes were applied as a label-free assay in sensing cysteine, as well as monitoring acetylcholinesterase (AChE) activity through the generated thiol-containing product. Furthermore, based on the toxicity effect of organophosphorus (OP) compounds on AChE, the robust membranes were successfully utilized to evaluate the toxicity of diverse OP compounds. The POD-like nanochannels open up an innovative way to expand the application of nanochannel-based electrochemical sensing platforms in drug inspection, food safety, and environmental pollution.
ESTHER : Xu_2021_Anal.Chem__
PubMedSearch : Xu_2021_Anal.Chem__
PubMedID: 34170111

Title : Neuroprotective effects of protocatechuic acid on sodium arsenate induced toxicity in mice: Role of oxidative stress, inflammation, and apoptosis - Li_2021_Chem.Biol.Interact__109392
Author(s) : Li Z , Liu Y , Wang F , Gao Z , Elhefny MA , Habotta OA , Abdel Moneim AE , Kassab RB
Ref : Chemico-Biological Interactions , :109392 , 2021
Abstract : Arsenic is a toxic metalloid abundantly found in nature and used in many industries. Consumption of contaminated water mainly results in human exposure to arsenic. Toxicity (arsenicosis) resulting from arsenic exposure causes cerebral neurodegeneration. Protocatechuic acid (PCA), a phenol derived from edible plants, has antioxidant properties. The present study investigated the neuroprotective potential of PCA against arsenic-induced neurotoxicity in mice. Male Swiss albino mice were divided into four groups: (i) orally administered physiological saline, (ii) orally administered 100 mg/kg PCA, (iii) orally administered 5 mg/kg NaAsO(2), and (iv) orally administered 100 mg/kg PCA 120 min prior to oral administration of 5 mg/kg NaAsO(2). Each group received its respective treatment for 1 week, after which cortical tissues from each group were analyzed for various parameters of oxidative stress, proinflammatory cytokines, apoptosis-related proteins, and changes in histopathology. NaAsO(2)-treatment resulted in a significant increase in lipid peroxidation (LPO), inducible nitric oxide synthetase (iNOs), and NO levels, with a decrease in the levels of both enzymatic (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and non-enzymatic (glutathione) antioxidant markers. Arsenic increased proinflammatory cytokine (tumor necrosis factor-alpha and interleukin-1beta) levels, enhanced caspase-3 and Bax expression, and reduced Bcl-2 expression. Furthermore, arsenic-exposure in mice decreased significantly acetylcholinesterase activity and brain-derived neurotrophic factor level in the cerebral cortex. Histopathological examination revealed changes in nerve cell cyto-architecture and distribution in arsenic-exposed brain tissue sections. PCA treatment before arsenic administration resulted in a positive shift in the oxidative stress and cytokine levels with decreased levels of LPO, iNOS, and NO. PCA pre-treatment considerably attenuated arsenic-associated histopathological changes in murine brain tissue. This study suggested that the presence of PCA may be responsible for the prevention of arsenic-induced neurotoxicity.
ESTHER : Li_2021_Chem.Biol.Interact__109392
PubMedSearch : Li_2021_Chem.Biol.Interact__109392
PubMedID: 33497687

Title : Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects - Han_2020_Eur.J.Med.Chem__113028
Author(s) : Han Y , Huang D , Xu S , Li L , Tian Y , Li S , Chen C , Li Y , Sun Y , Hou Y , Qin M , Gong P , Gao Z , Zhao Y
Ref : Eur Journal of Medicinal Chemistry , :113028 , 2020
Abstract : Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC(50) value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a "prodrug". In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.
ESTHER : Han_2020_Eur.J.Med.Chem__113028
PubMedSearch : Han_2020_Eur.J.Med.Chem__113028
PubMedID: 33248848

Title : Silicon-mediated multiple interactions: Simultaneous induction of rice defense and inhibition of larval performance and insecticide tolerance of Chilo suppressalis by sodium silicate - Wang_2020_Ecol.Evol_10_4816
Author(s) : Wang J , Xue R , Ju X , Yan H , Gao Z , Esmail Abdalla Elzaki M , Hu L , Zeng R , Song Y
Ref : Ecol Evol , 10 :4816 , 2020
Abstract : The rice striped stem borer (SSB, Chilo suppressalis) is one of the most destructive pests of rice plants. Si-mediated rice defense against various pests has been widely reported, and sodium silicate (SS) has been used as an effective source of silicon for application to plants. However, there is quite limited information about the direct effects of Si application on herbivorous insects. SSB larval performance and their insecticide tolerance were examined after they had been reared either on rice plants cultivated in nutrient solution containing 0.5 and 2.0 mM SS or on artificial diets with 0.1% and 0.5% SS. SS amendment in either rice culture medium or artificial diets significantly suppressed the enzymatic activities of acetylcholinesterase, glutathione S-transferases, and levels of cytochrome P450 protein in the midgut of C. suppressalis larvae. Larvae fed on diets containing SS showed lower insecticide tolerance. Additionally, RNA-seq analysis showed that SS-mediated larval insecticide tolerance was closely associated with fatty acid biosynthesis and pyruvate metabolism pathways. Our results suggest that Si not only enhances plant resistance against insect herbivore, but also impairs the insect's capacity to detoxify the insecticides. This should be considered as another important aspect in Si-mediated plant-insect interaction and may provide a novel approach of pest management.
ESTHER : Wang_2020_Ecol.Evol_10_4816
PubMedSearch : Wang_2020_Ecol.Evol_10_4816
PubMedID: 32551063

Title : Analysis of Differentially Expressed Transcripts in Apolygus lucorum (Meyer-Dur) Exposed to Different Temperature Coefficient Insecticides - An_2020_Int.J.Mol.Sci_21_658
Author(s) : An J , Liu C , Dou Y , Gao Z , Dang Z , Yan X , Pan W , Li Y
Ref : Int J Mol Sci , 21 :658 , 2020
Abstract : The existence of a temperature effect of insecticides frustrated the control of the green plant bug Apolygus lucorum (Meyer-Dur). Previous studies mostly focused on the application of insecticides, but the underlying mechanism remains incompletely understood. Here, we report a transcriptome profiling of A. lucorum treated by three kinds of temperature coefficient insecticides (TCIs) (positive TCI: imidacloprid, negative TCI: b-cypermethrin and non-effect TCI: phoxim) at 15 degrees C, 25 degrees C and 35 degrees C by using next- and third-generation RNA-Seq methods. A total of 34,739 transcripts were annotated from 277.74 Gb of clean data. There were more up-regulated transcripts than down-regulated transcripts in all three kinds of TCI treatments. Further Venn diagrams indicate the regulatory transcripts and regulatory modes were different at the three temperatures. The responses to imidacloprid involved more detox and stress response transcripts such as cytochrome P450 (CYP450), carboxylesterase (CarE) and catalase (CAT) at 35 degrees C, which was the case for beta-cypermethrin at 15 degrees C. UDP-glucuronyltransferase (UGT) and heat shock protein (HSP) transcripts were heavily involved, and thus deserve particular note in the temperature effect of insecticides. This high-confidence transcriptome atlas provides improved gene information for further study on the insecticide temperature effect related physiological and biochemical processes of A. lucorum.
ESTHER : An_2020_Int.J.Mol.Sci_21_658
PubMedSearch : An_2020_Int.J.Mol.Sci_21_658
PubMedID: 31963875

Title : Synthesis of functional ionic liquid modified magnetic chitosan nanoparticles for porcine pancreatic lipase immobilization - Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
Author(s) : Suo H , Gao Z , Xu L , Xu C , Yu D , Xiang X , Huang H , Hu Y
Ref : Mater Sci Eng C Mater Biol Appl , 96 :356 , 2019
Abstract : We developed magnetic chitosan nanoparticles (CSFe3O4) with mean diameter of 15-20nm. Subsequently, these inorganic-organic composite nanoparticles were modified using an imidazole-based functional ionic liquid (IL). The prepared support (ILCSFe3O4), which was used to immobilize porcine pancreatic lipase (PPL), was characterized using Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Circular dichroism (CD) was used to analyze the secondary structure of immobilized PPL. The immobilized PPL (PPLILCSFe3O4) exhibited 1.93-fold higher specific activity than PPLCS-Fe3O4 when triacetin was used as the substrate, and showed 95mg/g of lipase immobilization capacity and 382% of activity recovery. The residual activity of PPLILCSFe3O4 was above 60% of the initial activity after incubation at 50 degrees C for 6h, as was higher than that of PPLCSFe3O4 which showed 40% of the initial activity. In addition, PPLILCSFe3O4 retained 84.6% of the initial activity after 10cycles, whereas PPLCSFe3O4 retained only 75.5% activity. Furthermore, the kinetic parameters, apparent Km and Vmax of PPLILCSFe3O4 were 2.51mg/mL and 1.395U/mg respectively, these results indicated that the immobilized PPL had better affinity towards the substrate, especially when the nanoparticles were modified by functional IL. Besides, the magnetic chitosan nanoparticles loaded with PPL were easily recovered. A novel, efficient, and practical method for enzyme immobilization was developed.
ESTHER : Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
PubMedSearch : Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
PubMedID: 30606543

Title : A Unique Role of Carboxylesterase 3 (Ces3) in beta-Adrenergic Signaling-Stimulated Thermogenesis - Yang_2019_Diabetes_68_1178
Author(s) : Yang L , Li X , Tang H , Gao Z , Zhang K , Sun K
Ref : Diabetes , 68 :1178 , 2019
Abstract : Carboxylesterase 3 (Ces3) is a hydrolase with a wide range of activities in liver and adipose tissue. In this study, we identified Ces3 as a major lipid droplet surface-targeting protein in adipose tissue upon cold exposure by liquid chromatography-tandem mass spectrometry. To investigate the function of Ces3 in the beta-adrenergic signaling-activated adipocytes, we applied WWL229, a specific Ces3 inhibitor, or genetic inhibition by siRNA to Ces3 on isoproterenol (ISO)-treated 3T3-L1 and brown adipocyte cells. We found that blockage of Ces3 by WWL229 or siRNA dramatically attenuated the ISO-induced lipolytic effect in the cells. Furthermore, Ces3 inhibition led to impaired mitochondrial function measured by Seahorse. Interestingly, Ces3 inhibition attenuated an ISO-induced thermogenic program in adipocytes by downregulating Ucp1 and Pgc1alpha genes via peroxisome proliferator-activated receptor gamma. We further confirmed the effects of Ces3 inhibition in vivo by showing that the thermogenesis in adipose tissues was significantly attenuated in WWL229-treated or adipose tissue-specific Ces3 heterozygous knockout (Adn-Cre-Ces3(flx/wt)) mice. As a result, the mice exhibited dramatically impaired ability to defend their body temperature in coldness. In conclusion, our study highlights a lipolytic signaling induced by Ces3 as a unique process to regulate thermogenesis in adipose tissue.
ESTHER : Yang_2019_Diabetes_68_1178
PubMedSearch : Yang_2019_Diabetes_68_1178
PubMedID: 30862682
Gene_locus related to this paper: human-CES3 , mouse-Ces1d

Title : The pomegranate (Punica granatum L.) genome and the genomics of punicalagin biosynthesis - Qin_2017_Plant.J_91_1108
Author(s) : Qin G , Xu C , Ming R , Tang H , Guyot R , Kramer EM , Hu Y , Yi X , Qi Y , Xu X , Gao Z , Pan H , Jian J , Tian Y , Yue Z , Xu Y
Ref : Plant J , 91 :1108 , 2017
Abstract : Pomegranate (Punica granatum L.) is a perennial fruit crop grown since ancient times that has been planted worldwide and is known for its functional metabolites, particularly punicalagins. We have sequenced and assembled the pomegranate genome with 328 Mb anchored into nine pseudo-chromosomes and annotated 29 229 gene models. A Myrtales lineage-specific whole-genome duplication event was detected that occurred in the common ancestor before the divergence of pomegranate and Eucalyptus. Repetitive sequences accounted for 46.1% of the assembled genome. We found that the integument development gene INNER NO OUTER (INO) was under positive selection and potentially contributed to the development of the fleshy outer layer of the seed coat, an edible part of pomegranate fruit. The genes encoding the enzymes for synthesis and degradation of lignin, hemicelluloses and cellulose were also differentially expressed between soft- and hard-seeded varieties, reflecting differences in their accumulation in cultivars differing in seed hardness. Candidate genes for punicalagin biosynthesis were identified and their expression patterns indicated that gallic acid synthesis in tissues could follow different biochemical pathways. The genome sequence of pomegranate provides a valuable resource for the dissection of many biological and biochemical traits and also provides important insights for the acceleration of breeding. Elucidation of the biochemical pathway(s) involved in punicalagin biosynthesis could assist breeding efforts to increase production of this bioactive compound.
ESTHER : Qin_2017_Plant.J_91_1108
PubMedSearch : Qin_2017_Plant.J_91_1108
PubMedID: 28654223
Gene_locus related to this paper: prupe-a0a251r634 , pungr-a0a218xv87 , pungr-a0a218xi98 , pungr-a0a218wma5 , pungr-a0a218w0a8 , pungr-a0a218w138 , pungr-a0a218w7t6 , pungr-a0a218weu3 , pungr-a0a218xzu6

Title : AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress - Liu_2017_Angew.Chem.Int.Ed.Engl_56_8672
Author(s) : Liu Y , Fares M , Dunham NP , Gao Z , Miao K , Jiang X , Bollinger SS , Boal AK , Zhang X
Ref : Angew Chem Int Ed Engl , 56 :8672 , 2017
Abstract : Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins.
ESTHER : Liu_2017_Angew.Chem.Int.Ed.Engl_56_8672
PubMedSearch : Liu_2017_Angew.Chem.Int.Ed.Engl_56_8672
PubMedID: 28557281
Gene_locus related to this paper: rhoso-halo1

Title : TRPA1 channel mediates organophosphate-induced delayed neuropathy - Ding_2017_Cell.Discov_3_17024
Author(s) : Ding Q , Fang S , Chen X , Wang Y , Li J , Tian F , Xu X , Attali B , Xie X , Gao Z
Ref : Cell Discov , 3 :17024 , 2017
Abstract : The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.
ESTHER : Ding_2017_Cell.Discov_3_17024
PubMedSearch : Ding_2017_Cell.Discov_3_17024
PubMedID: 28894590

Title : Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation - Song_2016_J.Mol.Neurosci_60_115
Author(s) : Song J , Li N , Xia Y , Gao Z , Zou SF , Yan YH , Li SH , Wang Y , Meng YK , Yang JX , Kang TG
Ref : Journal of Molecular Neuroscience , 60 :115 , 2016
Abstract : Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-kappaB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-alpha and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKalpha and IKKbeta) expression and inhibit NF-kappaB signaling pathway activity; moreover, the increased miRNA-199a suppresses cholinesterases to increase cholinergic signaling, resulting in decreased expression of proinflammatory cytokines. ARC treatment confers protection for SH-SY5Y cells through positive regulation of miRNA expression, thereby reducing the inflammatory response. In turn, these effects accelerate injury repair in the scratch-induced injury model. These results might provide insights into the pharmacological role of ARC in anti-inflammation and neuroprotection in neural cells.
ESTHER : Song_2016_J.Mol.Neurosci_60_115
PubMedSearch : Song_2016_J.Mol.Neurosci_60_115
PubMedID: 27389368

Title : Enzymatic degradation of poly(butylene succinate) by cutinase cloned from Fusarium solani - Hu_2016_Polym.Degrad.Stab_134_211
Author(s) : Hu X , Gao Z , Wang Z , Su T , Yang L , Li P
Ref : Polymer Degradation and Stability , 134 :211 , 2016
Abstract : A gene encoding cutinase from Fusarium solani was cloned and overexpressed in Pichia pastoris. The recombinant cutinase with a molecular weight of 24 kDa was then purified to homogeneity. The enzyme presents degradation capacity for poly(butylene succinate) (PBS) and exhibits the optimum pH and temperature of 8.0 and 50 C, respectively. Enzyme activity is enhanced by K+ and Na+ and inhibited by Zn2+,Fe2+ ,Mn2+, and Co2+. The inhibitions of different chemicals on recombinant enzyme activity were examined. EDTA and b-mercaptoethanol exert significant inhibitory effect. The degradation of PBS films in the presence of the recombinant enzyme was further studied. Results showed that enzymatic degradation is a rapid process, and the PBS fi lms were degraded completely after approximately 6 h. The characteristics of PBS films after degradation were analyzed. With the extension of degradation time, the surfaces of PBS films became rougher and holes appeared with a gradually increasing trend. Differential scanning calorimetry and scanning electron microscopy analyses revealed that both amorphous and crystalline regions of PBS were degraded by the recombinant enzyme. Wide-angle X-ray diffractometer also indicated the crystallinity of PBS has a gradual downward trend with the extension of degradation time. Gel permeation chromatography showed the molecular weight of PBS has no obvious change before and after degradation.
ESTHER : Hu_2016_Polym.Degrad.Stab_134_211
PubMedSearch : Hu_2016_Polym.Degrad.Stab_134_211
PubMedID:
Gene_locus related to this paper: fusso-cutas

Title : Comparison of 10,11-Dehydrocurvularin Polyketide Synthases from Alternaria cinerariae and Aspergillus terreus Highlights Key Structural Motifs - Cochrane_2015_Chembiochem_16_2479
Author(s) : Cochrane RV , Gao Z , Lambkin GR , Xu W , Winter JM , Marcus SL , Tang Y , Vederas JC
Ref : Chembiochem , 16 :2479 , 2015
Abstract : Iterative typeI polyketide synthases (PKSs) from fungi are multifunctional enzymes that use their active sites repeatedly in a highly ordered sequence to assemble complex natural products. A phytotoxic macrolide with anticancer properties, 10,11-dehydrocurvularin (DHC), is produced by cooperation of a highly reducing (HR) iterative PKS and a non-reducing (NR) iterative PKS. We have identified the DHC gene cluster in Alternaria cinerariae, heterologously expressed the active HR PKS (Dhc3) and NR PKS (Dhc5) in yeast, and compared them to corresponding proteins that make DHC in Aspergillus terreus. Phylogenetic analysis and homology modeling of these enzymes identified variable surfaces and conserved motifs that are implicated in product formation.
ESTHER : Cochrane_2015_Chembiochem_16_2479
PubMedSearch : Cochrane_2015_Chembiochem_16_2479
PubMedID: 26493380
Gene_locus related to this paper: aspte-curs2 , altci-dhc5

Title : The neurovascular protective effects of huperzine a on d-galactose-induced inflammatory damage in the rat hippocampus - Ruan_2014_Gerontology_60_424
Author(s) : Ruan Q , Hu X , Ao H , Ma H , Gao Z , Liu F , Kong D , Bao Z , Yu Z
Ref : Gerontology , 60 :424 , 2014
Abstract : BACKGROUND: Chronic administration of D-galactose (D-gal) results in oxidative stress and chronic inflammatory aging. Age-related changes in the brain result in neurovascular damage and blood-brain barrier (BBB) dysfunction. However, little is known regarding D-gal-induced neurovascular damage, as well as the protective effects of huperzine A. OBJECTIVE: The purpose of this study was to utilize a D-gal-induced rat model to investigate the activation of neurovascular inflammatory damage and apoptosis in the rat hippocampus and to understand whether huperzine A alleviates D-gal-induced neuronal and vascular inflammatory injury.
METHODS: Aging rats were treated with D-gal (300 mg/kg s.c. for 8 weeks), were coadministered D-gal and huperzine A (D-gal 300 mg/kg and huperzine A 0.1 mg/kg s.c. for 8 weeks) or served as the saline-treated control group rats (same volume of saline given subcutaneously for 8 weeks). Changes in hippocampal morphology and biomarkers of inflammatory damage were analyzed.
RESULTS: Our study revealed that chronic administration of D-gal resulted in the activation of glia and vascular endothelial cells and upregulation of mRNA and protein levels of cell-associated adhesion molecules and inflammatory cytokines via nuclear factor (NF)-kappaB inhibitor degradation and NF-kappaB nuclear translocation. The inflammatory injury caused significant BBB dysfunction, decreased density of tight junctions (TJs) and apoptosis in the rat hippocampus. Coadministration of huperzine A not only markedly inhibited the D-gal-induced increase in acetylcholinesterase (AChE) activity, but also alleviated D-gal-induced neurovascular damage by inhibiting D-gal-induced NF-kappaB activation, improving cerebrovascular function and suppressing the D-gal-induced decrease in the density and protein levels of TJs and cell apoptosis.
CONCLUSIONS: Our findings provided evidence that D-gal induced a proinflammatory phenotype mediated by NF-kappaB in the rat hippocampus. Moreover, huperzine A suppressed D-gal-induced neurovascular damage and BBB dysfunction, partly by preventing NF-kappaB nuclear translocation. The inhibiting effect of huperzine A on AChE activity might play an important role in attenuating D-gal-induced inflammatory damage. (c) 2014 S. Karger AG, Basel.
ESTHER : Ruan_2014_Gerontology_60_424
PubMedSearch : Ruan_2014_Gerontology_60_424
PubMedID: 24969491

Title : Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors - Ji_2014_Eur.J.Med.Chem_86_242
Author(s) : Ji X , Xia C , Wang J , Su M , Zhang L , Dong T , Li Z , Wan X , Li J , Zhao L , Gao Z , Jiang H , Liu H
Ref : Eur Journal of Medicinal Chemistry , 86 :242 , 2014
Abstract : Based on the previous work in our group and the principle of computer-aided drug design, a series of novel beta-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 8l had moderate DPP4 inhibitory activity (IC50 = 0.05 muM) and good oral bioavailability (F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC50 = 0.01 muM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles (F = 22.8%, t1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9.
ESTHER : Ji_2014_Eur.J.Med.Chem_86_242
PubMedSearch : Ji_2014_Eur.J.Med.Chem_86_242
PubMedID: 25164763

Title : Comparative safety of the antifouling compound butenolide and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) to the marine medaka (Oryzias melastigma) - Chen_2014_Aquat.Toxicol_149C_116
Author(s) : Chen L , Ye R , Xu Y , Gao Z , Au DW , Qian PY
Ref : Aquat Toxicol , 149C :116 , 2014
Abstract : This study evaluated the potential adverse effects of butenolide, a promising antifouling compound, using the marine medaka (Oryzias melastigma), a model fish for marine ecotoxicology. The active ingredient used in the commercial antifoulant SeaNine 211, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) was employed as the positive control. Adult marine medaka (4-month-old) were exposed to various concentrations of butenolide or DCOIT for 28 days and then depurated in clean seawater for 14 days (recovery). A suite of sensitive biomarkers, including hepatic oxidative stress, neuronal signal transmission, endocrine disruption, and reproductive function, was used to measure significant biological effects induced by the chemicals. Compared to DCOIT, chronic exposure to butenolide induced a lower extent of oxidative stress in the liver of male and female medaka. Furthermore, butenolide-exposed fish could recover faster from oxidative stress than fish exposed to DCOIT. Regarding neurotransmission, DCOIT significantly inhibited acetylcholinesterase (AChE) activity in the brain of both male and female medaka, whereas this was not significant for butenolide. In addition, plasma estradiol (E2) level was elevated and testosterone (T) level was decreased in male medaka exposed to DCOIT. This greatly imbalanced sex hormones ratio (E2/T) in exposed males, indicating that DCOIT is a potent endocrine disruptive chemical. In contrast, butenolide induced only moderate effects on sex hormone levels in exposed males, which could be gradually recovered during depuration. Moreover, the endocrine disruptive effect induced by butenolide did not affect normal development of offspring. In contrast, DCOIT-exposed fish exhibited a decrease of egg production and impaired reproductive success. Overall, the above findings demonstrated that chronic exposure to butenolide induced transient, reversible biological effect on marine medaka, while DCOIT could impair reproductive success of fish, as evident by clear alterations of the E2/T ratio. The relatively low toxicity of butenolide on marine biota highlights its promising application in the antifouling industry. The present findings also emphasize gender difference in fish susceptibility to chemical treatment (male>female), which is an important consideration for ecological risk assessment.
ESTHER : Chen_2014_Aquat.Toxicol_149C_116
PubMedSearch : Chen_2014_Aquat.Toxicol_149C_116
PubMedID: 24583292

Title : Draft Genome Sequence of the Carrageenan-Degrading Bacterium Cellulophaga sp. Strain KL-A, Isolated from Decaying Marine Algae - Shan_2014_Genome.Announc_2_e00145
Author(s) : Shan D , Ying J , Li X , Gao Z , Wei G , Shao Z
Ref : Genome Announc , 2 : , 2014
Abstract : Cellulophaga sp. strain KL-A, isolated from decaying marine algae, is able to degrade iota-carrageenan. Here, we report the draft genome sequence of Cellulophaga sp. strain KL-A.
ESTHER : Shan_2014_Genome.Announc_2_e00145
PubMedSearch : Shan_2014_Genome.Announc_2_e00145
PubMedID: 24604651
Gene_locus related to this paper: 9flao-w7qzl1

Title : Draft Genome Sequence of the Agar-Degrading Bacterium Catenovulum sp. Strain DS-2, Isolated from Intestines of Haliotis diversicolor - Shan_2014_Genome.Announc_2_e00144
Author(s) : Shan D , Li X , Gu Z , Wei G , Gao Z , Shao Z
Ref : Genome Announc , 2 : , 2014
Abstract : Catenovulum sp. strain DS-2, isolated from intestines of Haliotis diversicolor, is able to degrade agar and produce agaro-oligosaccharides. Here, we report the draft genome sequence of Catenovulum sp. strain DS-2.
ESTHER : Shan_2014_Genome.Announc_2_e00144
PubMedSearch : Shan_2014_Genome.Announc_2_e00144
PubMedID: 24604650
Gene_locus related to this paper: 9alte-w7qh33 , 9alte-w7r197

Title : Metabolism and pharmacokinetics of allitinib in cancer patients: the roles of cytochrome p450s and epoxide hydrolase in its biotransformation - Lin_2014_Drug.Metab.Dispos_42_872
Author(s) : Lin L , Xie C , Gao Z , Chen X , Zhong D
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 42 :872 , 2014
Abstract : Allitinib, a novel irreversible selective inhibitor of the epidermal growth factor receptor (EGFR) 1 and human epidermal receptor 2 (ErbB2), is currently in clinical trials in China for the treatment of solid tumors. It is a structural analog of lapatinib but has an acrylamide side chain. Sixteen metabolites of allitinib were detected by ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. The pharmacologically active alpha,beta-unsaturated carbonyl group was the major metabolic site. The metabolic pathways included O-dealkylation, amide hydrolysis, dihydrodiol formation, hydroxylation, and secondary phase 2 conjugation. The metabolite of amide hydrolysis (M6) and 27,28-dihydrodiol allitinib (M10) were the major pharmacologically active metabolites in the circulation. The steady-state exposures to M6 and M10 were 11% and 70% of that of allitinib, respectively. The biotransformation of allitinib was determined using microsomes and recombinant metabolic enzymes. In vitro phenotyping studies demonstrated that multiple cytochrome P450 (P450) isoforms, mainly CYP3A4/5 and CYP1A2, were involved in the metabolism of allitinib. Thiol conjugates (M14 and M16) and dihydrodiol metabolites (M5 and M10) were detected in humans, implying the formation of reactive intermediates. The formation of a glutathione conjugate of allitinib was independent of NADPH and P450 isoforms, but was catalyzed by glutathione-S-transferase. P450 enzymes and epoxide hydrolase were involved in M10 formation. Overall, our study showed that allitinib was metabolized by the O-dealkylation pathway similar to lapatinib, but that amide hydrolysis and the formation of dihydrodiol were the dominant metabolic pathways. The absorbed allitinib was extensively metabolized by multiple enzymes.
ESTHER : Lin_2014_Drug.Metab.Dispos_42_872
PubMedSearch : Lin_2014_Drug.Metab.Dispos_42_872
PubMedID: 24598282

Title : A novel protein elicitor (SsCut) from Sclerotinia sclerotiorum induces multiple defense responses in plants - Zhang_2014_Plant.Mol.Biol_86_495
Author(s) : Zhang H , Wu Q , Cao S , Zhao T , Chen L , Zhuang P , Zhou X , Gao Z
Ref : Plant Mol Biol , 86 :495 , 2014
Abstract : In this study, we report the cloning of the SsCut gene encoding cutinase from Sclerotinia sclerotiorum. We isolated a 609-bp cDNA encoding a polypeptide of 202 amino acids with a molecular weight of 20.4 kDa. Heterologous expression of SsCut in Escherichia coli (His-SsCut) caused the formation of lesions in tobacco that closely resembled hypersensitive response lesions. Mutational analysis identified the C-terminal-half peptide and the same amino acids indispensable for both enzyme and elicitor activity. His-SsCut was caused cell death in Arabidopsis, soybean (Glycine max), oilseed rape (Brassica napus), rice (Oryza sativa), maize (Zea mays), and wheat (Triticum aestivum), indicating that both dicot and monocot species are responsive to the elicitor. Furthermore, the elicitation of tobacco was effective in the induction of the activities of hydrogen peroxide, phenylalanine ammonia-lyase, peroxides, and polyphenol oxidase. His-SsCut-treated plants exhibited enhanced resistance as indicated by a significant reduction in the number and size of S. sclerotiorum, Phytophthora sojae, and P. nicotianae lesions on leaves relative to controls. Real-time PCR results indicated that the expression of defense-related genes and genes involved in signal transduction were induced by His-SsCut. Our results demonstrate that SsCut is an elicitor that triggers defense responses in plants and will help to clarify its relationship to downstream signaling pathways that induce defense responses.
ESTHER : Zhang_2014_Plant.Mol.Biol_86_495
PubMedSearch : Zhang_2014_Plant.Mol.Biol_86_495
PubMedID: 25149470

Title : Structure of the type VI secretion phospholipase effector Tle1 provides insight into its hydrolysis and membrane targeting - Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175
Author(s) : Hu H , Zhang H , Gao Z , Wang D , Liu G , Xu J , Lan K , Dong Y
Ref : Acta Crystallographica D Biol Crystallogr , 70 :2175 , 2014
Abstract : A diverse superfamily of phospholipases consisting of the type VI lipase effectors Tle1-Tle5 secreted by the bacterial type VI secretion system (T6SS) have recently been identified as antibacterial effectors that hydrolyze membrane phospholipids. These effectors show no significant homology to known lipases, and their mechanism of membrane targeting and hydrolysis of phospholipids remains unknown. Here, the crystal structure of Tle1 ( approximately 96.5 kDa) from Pseudomonas aeruginosa refined to 2.0 A resolution is reported, representing the first structure of this superfamily. Its overall structure can be divided into two distinct parts, the phospholipase catalytic module and the putative membrane-anchoring module; this arrangement has not previously been observed in known lipase structures. The phospholipase catalytic module has a canonical alpha/beta-hydrolase fold and mutation of any residue in the Ser-Asp-His catalytic triad abolishes its toxicity. The putative membrane-anchoring module adopts an open conformation composed of three amphipathic domains, and its partial folds are similar to those of several periplasmic or membrane proteins. A cell-toxicity assay revealed that the putative membrane-anchoring module is critical to Tle1 antibacterial activity. A molecular-dynamics (MD) simulation system in which the putative membrane-anchoring module embedded into a bilayer was stable over 50 ns. These structure-function studies provide insight into the hydrolysis and membrane-targeting process of the unique phospholipase Tle1.
ESTHER : Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175
PubMedSearch : Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175
PubMedID: 25084336
Gene_locus related to this paper: pseae-q9hyv3

Title : Genetic amplification of PPME1 in gastric and lung cancer and its potential as a novel therapeutic target - Li_2014_Cancer.Biol.Ther_15_128
Author(s) : Li J , Han S , Qian Z , Su X , Fan S , Fu J , Liu Y , Yin X , Gao Z , Zhang J , Yu DH , Ji Q
Ref : Cancer Biol Ther , 15 :128 , 2014
Abstract : Protein phosphatase methylesterase 1 (PPME1) is a protein phosphatase 2A (PP2A)-specific methyl esterase that negatively regulates PP2A through demethylation at its carboxy terminal leucine 309 residue. Emerging evidence shows that the upregulation of PPME1 is associated with poor prognosis in glioblastoma patients. By performing an array comparative genomic hybridization analysis to detect copy number changes, we have been the first to identify PPME1 gene amplification in 3.8% (5/131) of Chinese gastric cancer (GC) samples and 3.1% (4/124) of Chinese lung cancer (LC) samples. This PPME1 gene amplification was confirmed by fluorescence in situ hybridization analysis and is correlated with elevated protein expression, as determined by immunohistochemistry analysis. To further investigate the role of PPME1 amplification in tumor growth, short-hairpin RNA-mediated gene silencing was employed. A knockdown of PPME1 expression resulted in a significant inhibition of cell proliferation and induction of cell apoptosis in PPME1-amplified human cancer cell lines SNU668 (GC) and Oka-C1 (LC), but not in nonamplified MKN1 (GC) and HCC95 (LC) cells. The PPME1 gene knockdown also led to a consistent decrease in PP2A demethylation at leucine 309, which was correlated with the downregulation of cellular Erk and AKT phosphorylation. Our data indicate that PPME1 could be an attractive therapeutic target for a subset of GCs and LCs.
ESTHER : Li_2014_Cancer.Biol.Ther_15_128
PubMedSearch : Li_2014_Cancer.Biol.Ther_15_128
PubMedID: 24253382
Gene_locus related to this paper: human-PPME1

Title : Fusaric acid induction of programmed cell death modulated through nitric oxide signalling in tobacco suspension cells - Jiao_2013_Planta_238_727
Author(s) : Jiao J , Zhou B , Zhu X , Gao Z , Liang Y
Ref : Planta , 238 :727 , 2013
Abstract : Fusaric acid (FA) is a nonhost-selective toxin mainly produced by Fusarium oxysporum, the causal agent of plant wilt diseases. We demonstrate that FA can induce programmed cell death (PCD) in tobacco suspension cells and the FA-induced PCD is modulated by nitric oxide (NO) signalling. Cells undergoing cell death induced by FA treatment exhibited typical characteristics of PCD including cytoplasmic shrinkage, chromatin condensation, DNA fragmentation, membrane plasmolysis, and formation of small cytoplasmic vacuoles. In addition, caspase-3-like activity was activated upon the FA treatment. The process of FA-induced PCD was accompanied by a rapid accumulation of NO in a FA dose-dependent manner. Pre-treatment of cells with NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) or NO synthase inhibitor N(G)-monomethyl-arginine monoacetate (L-NMMA) significantly reduced the rate of FA-induced cell death. Furthermore, the caspase-3-like activity and the expression of PAL and Hsr203J genes were alleviated by application of cPTIO or L-NMMA to FA-treated tobacco cells. This indicates that NO is an important factor involved in the FA-induced PCD. Our results also show that pre-treatment of tobacco cells with a caspase-3-specific inhibitor, Ac-DEVD-CHO, can reduce the rate of FA-induced cell death. These results demonstrate that the FA-induced cell death is a PCD and is modulated by NO signalling through caspase-3-like activation.
ESTHER : Jiao_2013_Planta_238_727
PubMedSearch : Jiao_2013_Planta_238_727
PubMedID: 23838885
Gene_locus related to this paper: gibf5-fub4 , gibf5-fub5

Title : The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats - Ruan_2013_Mech.Ageing.Dev_134_89
Author(s) : Ruan Q , Liu F , Gao Z , Kong D , Hu X , Shi D , Bao Z , Yu Z
Ref : Mech Ageing Dev , 134 :89 , 2013
Abstract : Oxidative stress contributes to a chronic inflammatory process referred to as "inflamm-aging". Acetylcholinesterase inhibitors (AChEI) can enhance cholinergic transmission and act as anti-inflammatory agents via immunocompetent cells expressing alpha-7 acetylcholine receptors (AChR). The present study explores the possible role of huperzine A, a reversible and selective AChEI, against D-gal-induced oxidative damage, cell toxicity and inflamm-aging in rat livers. In two-month-old rats with normal liver function, an 8-week administration of D-gal (300 mg/kg subcutaneously (s.c.) injected), significantly increased hepatic impairment, ROS generation and oxidative damage, hepatic senescence, nuclear factor-kappa B (NF-kappaB) activation and inflammatory responses. An 8-week co-administration of both D-gal (300 mg/kg s.c.) and huperzine A (0.1 mg/kg s.c.) not only significantly decreased hepatic function impairment, ROS generation, oxidative damage, but also suppressed inflamm-aging by inhibiting hepatic replicative senescence, AChE activity, IkappaBalpha degradation, NF-kappaB p65 nuclear translocation and inflammatory responses. The expression levels of pro-inflammatory cytokine mRNA and proteins, such as TNFalpha, IL-1beta and IL-6 decrease significantly, and the protein levels of the anti-inflammatory cytokine IL-10 display an obvious increase. These findings indicated that D-gal-induced hepatic injury and inflamm-aging in the rat liver was associated with the development of a pro-inflammatory phenotype in this organ. D-gal induced damage-associated molecular patterns (DAMPs) because oxidative damages might play an important role in D-gal-induced hepatic sterile inflammation. Huperzine A exhibited protective effects against D-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-kappaB nuclear localization and activation.
ESTHER : Ruan_2013_Mech.Ageing.Dev_134_89
PubMedSearch : Ruan_2013_Mech.Ageing.Dev_134_89
PubMedID: 23313706

Title : The genome of the hydatid tapeworm Echinococcus granulosus - Zheng_2013_Nat.Genet_45_1168
Author(s) : Zheng H , Zhang W , Zhang L , Zhang Z , Li J , Lu G , Zhu Y , Wang Y , Huang Y , Liu J , Kang H , Chen J , Wang L , Chen A , Yu S , Gao Z , Jin L , Gu W , Wang Z , Zhao L , Shi B , Wen H , Lin R , Jones MK , Brejova B , Vinar T , Zhao G , McManus DP , Chen Z , Zhou Y , Wang S
Ref : Nat Genet , 45 :1168 , 2013
Abstract : Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
ESTHER : Zheng_2013_Nat.Genet_45_1168
PubMedSearch : Zheng_2013_Nat.Genet_45_1168
PubMedID: 24013640
Gene_locus related to this paper: echgr-k4epc5 , echmu-u6hbw4 , echgr-w6ugl0 , echgr-w6u7y4 , echgr-w6vaq5 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , echgr-a0a068wl60

Title : Enzymatic synthesis of resorcylic acid lactones by cooperation of fungal iterative polyketide synthases involved in hypothemycin biosynthesis - Zhou_2010_J.Am.Chem.Soc_132_4530
Author(s) : Zhou H , Qiao K , Gao Z , Meehan MJ , Li JW , Zhao X , Dorrestein PC , Vederas JC , Tang Y
Ref : Journal of the American Chemical Society , 132 :4530 , 2010
Abstract : Hypothemycin is a macrolide protein kinase inhibitor from the fungus Hypomyces subiculosus. During biosynthesis, its carbon framework is assembled by two iterative polyketide synthases (PKSs), Hpm8 (highly reducing) and Hpm3 (nonreducing). These were heterologously expressed in Saccharomyces cerevisiae BJ5464-NpgA, purified to near homogeneity, and reconstituted in vitro to produce (6'S,10'S)-trans-7',8'-dehydrozearalenol (1) from malonyl-CoA and NADPH. The structure of 1 was determined by X-ray crystallographic analysis. In the absence of functional Hpm3, the reducing PKS Hpm8 produces and offloads truncated pyrone products instead of the expected hexaketide. The nonreducing Hpm3 is able to accept an N-acetylcysteamine thioester of a correctly functionalized hexaketide to form 1, but it is unable to initiate polyketide formation from malonyl-CoA. We show that the starter-unit:ACP transacylase (SAT) of Hpm3 is critical for crosstalk between the two enzymes and that the rate of biosynthesis of 1 is determined by the rate of hexaketide formation by Hpm8.
ESTHER : Zhou_2010_J.Am.Chem.Soc_132_4530
PubMedSearch : Zhou_2010_J.Am.Chem.Soc_132_4530
PubMedID: 20222707
Gene_locus related to this paper: hypsb-hpm3

Title : Dwarf 88, a novel putative esterase gene affecting architecture of rice plant - Gao_2009_Plant.Mol.Biol_71_265
Author(s) : Gao Z , Qian Q , Liu X , Yan M , Feng Q , Dong G , Liu J , Han B
Ref : Plant Mol Biol , 71 :265 , 2009
Abstract : Rice architecture is an important agronomic trait that affects grain yield. We characterized a tillering dwarf mutant d88 derived from Oryza sativa ssp. japonica cultivar Lansheng treated with EMS. The mutant had excessive shorter tillers and smaller panicles and seeds compared to the wild-type. A reduction in number and size of parenchyma cells around stem marrow cavity as well as a delay in the elongation of parenchyma cells caused slender tillers and dwarfism in the d88 mutant. The D88 gene was isolated via map-based cloning and identified to encode a putative esterase. The gene was expressed in most rice organs, with especially high levels in the vascular tissues. The mutant carried a nucleotide substitution in the first exon of the gene that led to the substitution of arginine for glycine, which presumably disrupted the functionally conserved N-myristoylation domain of the protein. The function of the gene was confirmed by complementation test and antisense analysis. D88, thus, represents a new category of genes that regulates cell growth and organ development and consequently plant architecture. The potential relationship between the tiller formation associated genes and D88 is discussed and future identification of the substrate for D88 may lead to the characterization of new pathways regulating plant development.
ESTHER : Gao_2009_Plant.Mol.Biol_71_265
PubMedSearch : Gao_2009_Plant.Mol.Biol_71_265
PubMedID: 19603144
Gene_locus related to this paper: orysj-Q10QA5

Title : Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in Pichia pastoris - Gao_2009_Biosci.Biotechnol.Biochem_73_688
Author(s) : Gao Z , Bai G , Chen J , Zhang Q , Pan P , Bai F , Geng P
Ref : Biosci Biotechnol Biochem , 73 :688 , 2009
Abstract : Glucagon-like peptide-1 (GLP-1) has considerable potential as a possible therapeutic agent for type-2 diabetes. Unfortunately, this glucoincretin is short lived due to degradation by dipeptidyl-peptidase IV and rapid clearance by renal filtration. In this study, we attempted to extend GLP-1 action through the attachment of a lysine residue at the N-terminal of GLP-1 (named KGLP-1), and to make a fusion protein with human serum albumin (HSA) in Pichia pastoris. The protein, designated KGLP-1/HSA, was purified by an immunomagnetic separation technique. High performance liquid chromatography (HPLC) showed that the purified protein had an overall purity of 92.0%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the expected molecular mass of 70,297.8 Da. Additionally, the N-terminal sequence of KGLP-1/HSA was confirmed by N-terminal sequencing. The stability and biological activity of KGLP-1/HSA were then evaluated in vitro and in vivo. The findings indicated that fusion KGLP-1/HSA preserved the action of native GLP-1, and the active duration was greatly prolonged.
ESTHER : Gao_2009_Biosci.Biotechnol.Biochem_73_688
PubMedSearch : Gao_2009_Biosci.Biotechnol.Biochem_73_688
PubMedID: 19270384

Title : A putative lipase gene EXTRA GLUME1 regulates both empty-glume fate and spikelet development in rice - Li_2009_Plant.J_57_593
Author(s) : Li H , Xue D , Gao Z , Yan M , Xu W , Xing Z , Huang D , Qian Q , Xue Y
Ref : Plant J , 57 :593 , 2009
Abstract : Recent studies have shown that molecular control of inner floral organ identity appears to be largely conserved between monocots and dicots, but little is known regarding the molecular mechanism underlying development of the monocot outer floral organ, a unique floral structure in grasses. In this study, we report the cloning of the rice EXTRA GLUME1 (EG1) gene, a putative lipase gene that specifies empty-glume fate and floral meristem determinacy. In addition to affecting the identity and number of empty glumes, mutations in EG1 caused ectopic floral organs to be formed at each organ whorl or in extra ectopic whorls. Iterative glume-like structures or new floral organ primordia were formed in the presumptive region of the carpel, resulting in an indeterminate floral meristem. EG1 is expressed strongly in inflorescence primordia and weakly in developing floral primordia. We also found that the floral meristem and organ identity gene OsLHS1 showed altered expression with respect to both pattern and levels in the eg1 mutant, and is probably responsible for the pleiotropic floral defects in eg1. As a putative class III lipase that functionally differs from any known plant lipase, EG1 reveals a novel pathway that regulates rice empty-glume fate and spikelet development.
ESTHER : Li_2009_Plant.J_57_593
PubMedSearch : Li_2009_Plant.J_57_593
PubMedID: 18980657

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : One-step purification of a fusion protein of glucagon-like peptide-1 and human serum albumin expressed in pichia pastoris by an immunomagnetic separation technique - Chen_2007_Biosci.Biotechnol.Biochem_71_2655
Author(s) : Chen J , Bai G , Cao Y , Gao Z , Zhang Q , Zhu Y , Yang W
Ref : Biosci Biotechnol Biochem , 71 :2655 , 2007
Abstract : Glucagon-like peptide-1 (GLP-1) has great therapeutic potential to treat diabetes type 2, mainly due to its unique glucose-dependent stimulation of insulin secretion profiles, but its clinical application is limited by its short half-life in vivo, which resultes from degradation by dipeptidyl peptidase IV and/or renal clearance. Developing long-acting GLP-1 analogs is therefore an important step toward using them therapeutically. In this study, the GLP-1/human serum albumin (HSA) fusion protein gene was cloned into the secretor type expression vector pPIC9K and subsequently expressed in Pichia pastoris. The expression quantity reached 58.5 mg/l in small-scale incubation. After optimization and characterization, the GLP-1/HSA fusion protein was successfully purified from the supernatant of the broth using immunomagnetic cellulose microspheres. HPLC showed that the purified GLP-1/HSA had an overall purity of 93.9%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the fusion protein exhibited the expected molecular mass of 70 kDa. Furthermore, that analysis of in vivo activity indicated that GLP-1/HSA reduced the blood glucose level after intraperitoneal administration to Chinese Kunming mice in a dose-dependent manner, and the effects held significantly 4 h after administration. Overall, this study illustrates the development of a long-acting GLP-1/HSA fusion protein expressed in Pichia pastoris.
ESTHER : Chen_2007_Biosci.Biotechnol.Biochem_71_2655
PubMedSearch : Chen_2007_Biosci.Biotechnol.Biochem_71_2655
PubMedID: 17986790