Gao L

References (46)

Title : Inhibition of soluble epoxide hydrolase enhances the dentin-pulp complex regeneration mediated by crosstalk between vascular endothelial cells and dental pulp stem cells - Kong_2024_J.Transl.Med_22_61
Author(s) : Kong L , Li J , Bai Y , Xu S , Zhang L , Chen W , Gao L , Wang F
Ref : J Transl Med , 22 :61 , 2024
Abstract : BACKGROUND: Revascularization and restoration of normal pulp-dentin complex are important for tissue-engineered pulp regeneration. Recently, a unique periodontal tip-like endothelial cells subtype (POTCs) specialized to dentinogenesis was identified. We have confirmed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor targeting epoxyeicosatrienoic acids (EETs) metabolism, promotes bone growth and regeneration by angiogenesis and osteogenesis coupling. We hypothesized that TPPU could also promote revascularization and induce POTCs to contribute to pulp-dentin complex regeneration. Here, we in vitro and in vivo characterized the potential effect of TPPU on the coupling of angiogenesis and odontogenesis and investigated the relevant mechanism, providing new ideas for pulp-dentin regeneration by targeting sEH. METHODS: In vitro effects of TPPU on the proliferation, migration, and angiogenesis of dental pulp stem cells (DPSCs), human umbilical vein endothelial cells (HUVECs) and cocultured DPSCs and HUVECs were detected using cell counting kit 8 (CCK8) assay, wound healing, transwell, tube formation and RT-qPCR. In vivo, Matrigel plug assay was performed to outline the roles of TPPU in revascularization and survival of grafts. Then we characterized the VEGFR2 + POTCs around odontoblast layer in the molar of pups from C57BL/6 female mice gavaged with TPPU. Finally, the root segments with DPSCs mixed with Matrigel were implanted subcutaneously in BALB/c nude mice treated with TPPU and the root grafts were isolated for histological staining. RESULTS: In vitro, TPPU significantly promoted the migration and tube formation capability of cocultured DPSCs and HUVECs. ALP and ARS staining and RT-qPCR showed that TPPU promoted the osteogenic and odontogenic differentiation of cultured cells, treatment with an anti-TGF-beta blocking antibody abrogated this effect. Knockdown of HIF-1alpha in HUVECs significantly reversed the effect of TPPU on the expression of angiogenesis, osteogenesis and odontogenesis-related genes in cocultured cells. Matrigel plug assay showed that TPPU increased VEGF/VEGFR2-expressed cells in transplanted grafts. TPPU contributed to angiogenic-odontogenic coupling featured by increased VEGFR2 + POTCs and odontoblast maturation during early dentinogenesis in molar of newborn pups from C57BL/6 female mice gavaged with TPPU. TPPU induced more dental pulp-like tissue with more vessels and collagen fibers in transplanted root segment. CONCLUSIONS: TPPU promotes revascularization of dental pulp regeneration by enhancing migration and angiogenesis of HUVECs, and improves odontogenic differentiation of DPSCs by TGF-beta. TPPU boosts the angiogenic-odontogenic coupling by enhancing VEGFR2 + POTCs meditated odontoblast maturation partly via upregulating HIF-1alpha, which contributes to increasing pulp-dentin complex for tissue-engineered pulp regeneration.
ESTHER : Kong_2024_J.Transl.Med_22_61
PubMedSearch : Kong_2024_J.Transl.Med_22_61
PubMedID: 38229161

Title : Whole-brain neural connectivity to cholinergic neurons in the nucleus basalis of Meynert - Chen_2023_J.Neurochem_17thISCM_166_233
Author(s) : Chen ZY , Yang YL , Li M , Gao L , Qu WM , Huang ZL , Yuan XS
Ref : Journal of Neurochemistry , 166 :233 , 2023
Abstract : The cholinergic neurons in the nucleus basalis of Meynert (NBM) are a key structure in cognition, the dysfunction of which is associated with various neurological disorders, especially dementias. However, the whole-brain neural connectivity to cholinergic neurons in the NBM remains to be further and comprehensively researched. Using virus-based, specific, retrograde, and anterograde tracing, we illustrated the monosynaptic inputs and axon projections of NBM cholinergic neurons in choline acetyltransferase (ChAT)-Cre transgenic mice. Our results showed that NBM cholinergic neurons received mainly inputs from the caudate putamen and the posterior limb of the anterior commissure in the subcortex. Moreover, the majority of cholinergic terminals from the NBM were observed in the cortex mantle, including the motor cortex, sensory cortex, and visual cortex. Interestingly, although NBM cholinergic neurons received input projections from the caudate putamen, interstitial nucleus of the posterior limb of the anterior commissure, and central amygdaloid nucleus, NBM cholinergic neurons sparsely sent axon projection to innervate these areas. Furthermore, primary motor cortex, secondary motor cortex, and primary somatosensory cortex received abundant inputs from the NBM but sent few outputs to the NBM. Taken together, our results reveal the detailed and specific connectivity of cholinergic neurons of the NBM and provide a neuroanatomic foundation for further studies to explore the important physiological functions of NBM cholinergic neurons.
ESTHER : Chen_2023_J.Neurochem_17thISCM_166_233
PubMedSearch : Chen_2023_J.Neurochem_17thISCM_166_233
PubMedID: 37353897

Title : Antennae-enriched expression of candidate odorant degrading enzyme genes in the turnip aphid, Lipaphis erysimi - Shangguan_2023_Front.Physiol_14_1228570
Author(s) : Shangguan C , Kuang Y , Gao L , Zhu B , Chen XD , Yu X
Ref : Front Physiol , 14 :1228570 , 2023
Abstract : Aphids heavily rely on their olfactory system for foraging behavior. Odorant-degrading enzymes (ODEs) are essential in preserving the olfactory acuity of aphids by removing redundant odorants in the antennae. Certain enzymes within this group stand out as being enriched and/or biased expressed in the antennae, such as carboxylesterases (CXEs), cytochrome P450 (CYPs), glutathione S-transferases (GSTs), and UDP-glycosyltransferases (UGTs). Here, we performed a comparative transcriptome analysis of antennae and body tissue to isolate the antennal ODE genes of turnip aphid Lipaphis erysimi. A dataset of one CXE, seven CYPs, two GSTs, and five UGTs enriched in the antennae was identified and subjected to sequence analysis. Furthermore, qRT-PCR analyses showed that 13 ODE genes (LeCXE6, LeCYP4c1, LeCYP6a2, LeCYP6a13, LeCYP6a14.2, LeCYP6k1, LeCYP18a1, LeGST1, LeUGT1-7, LeUGT2B7, LeUGT2B13, LeUGT2C1.1, and LeUGT2C1.2) were specifically or significantly elevated in antennal tissues. Among these antennae-enriched ODEs, LeCYP4c1, LeCYP6a2, LeCYP6a13, LeCYP6a14.2, LeCYP18a1, LeUGT2B7, and LeUGT2B13 were found to exhibit significantly higher expression levels in alate aphids compared to apterous and nymph aphids, suggesting their putative role in detecting new host plant location. The results presented in this study highlight the identification and expression of ODE genes in L. erysimi, paving the path to investigate their functional role in odorant degradation during the olfactory processes.
ESTHER : Shangguan_2023_Front.Physiol_14_1228570
PubMedSearch : Shangguan_2023_Front.Physiol_14_1228570
PubMedID: 37476684
Gene_locus related to this paper: 9hemi-LeCXE6

Title : Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes - Sun_2023_Endocrine__
Author(s) : Sun S , Gong S , Li M , Wang X , Wang F , Cai X , Liu W , Luo Y , Zhang S , Zhang R , Zhou L , Zhu Y , Ma Y , Ren Q , Zhang X , Chen J , Chen L , Wu J , Gao L , Zhou X , Li Y , Zhong L , Han X , Ji L
Ref : Endocrine , : , 2023
Abstract : OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
ESTHER : Sun_2023_Endocrine__
PubMedSearch : Sun_2023_Endocrine__
PubMedID: 37726640

Title : Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial - Ji_2023_Diabetes.Obes.Metab_25_3671
Author(s) : Ji L , Lu J , Gao L , Ying C , Sun J , Han J , Zhao W , Gao Y , Wang K , Zheng X , Xie D , Ding J , Zhao J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3671 , 2023
Abstract : AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedID: 37661308

Title : A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy - Ji_2023_Diabetes.Obes.Metab_25_3788
Author(s) : Ji L , Lu J , Gao L , Yan X , Li J , Cheng Z , Zhang L , Tian J , Li P , Bai J , Xie D , Zhao J , Ding J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3788 , 2023
Abstract : AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100mg, cetagliptin 50mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50mg and placebo were switched to cetagliptin 100mg for 28weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17+/-0.794%, -1.23+/-0.896% in cetagliptin 100mg and 50mg plus metformin group, respectively. No difference was observed between the cetagliptin 100mg and 50mg plus metformin group. Patients with higher baseline HbA1c levels (<=8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100mg (49.4%) and cetagliptin 50mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment beta-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedID: 37724698

Title : Targeting soluble epoxide hydrolase promotes osteogenic-angiogenic coupling via activating SLIT3\/HIF-1alpha signalling pathway - Gao_2023_Cell.Prolif__e13403
Author(s) : Gao L , Chen W , Li L , Li J , Kongling W , Zhang Y , Yang X , Zhao Y , Bai J , Wang F
Ref : Cell Prolif , :e13403 , 2023
Abstract : Type H vessels have recently been identified to modulate osteogenesis. Epoxyeicostrioleic acids (EETs) have an essential contribution to vascular homeostasis. However, whether increased EETs with soluble epoxide hydrolase (sEH) inhibitor TPPU enhance the coupling of angiogenesis and osteogenesis remains largely unknown. The effects of TPPU on cross-talk between co-cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs), and on long bone growth and calvarial defect repair in mice were investigated in vitro and in vivo. TPPU enhanced osteogenic differentiation of co-cultured HUVECs and hDPSCs in vitro and increased type H vessels, and long bone growth and bone repair of calvarial defect. Mechanistically, TPPU promoted cell proliferation and angiogenesis, reclined cell apoptosis, and significantly increased CD31(hi) EMCN(hi) endothelial cells (ECs) and SLIT3 and HIF-1alpha expression levels in co-cultured HUVECs and hDPSCs. Knockdown of Slit3 in hDPSCs or Hif-1alpha in HUVECs impaired the formation of CD31(hi) EMCN(hi) ECs and reversed TPPU-induced osteogenesis. We defined a previously unidentified effect of TPPU coupling angiogenesis and osteogenesis. TPPU induced type H vessels by upregulating the expression of hDPSCs-derived SLIT3, which resulted in the activation of ROBO1/YAP1/HIF-1alpha signalling pathway in ECs. Targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a promising therapeutic target for bone regeneration and repair.
ESTHER : Gao_2023_Cell.Prolif__e13403
PubMedSearch : Gao_2023_Cell.Prolif__e13403
PubMedID: 36636821

Title : Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers - Li_2023_Clinics.(Sao.Paulo)_78_100208
Author(s) : Li J , Wen Z , Lou Y , Chen J , Gao L , Li X , Wang F
Ref : Clinics (Sao Paulo) , 78 :100208 , 2023
Abstract : OBJECTIVE: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. METHODS: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. RESULTS: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. CONCLUSIONS: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.
ESTHER : Li_2023_Clinics.(Sao.Paulo)_78_100208
PubMedSearch : Li_2023_Clinics.(Sao.Paulo)_78_100208
PubMedID: 37148830

Title : Time-resolved fluorescence nanoprobe of acetylcholinesterase based on ZnGeO:Mn luminescence nanorod modified with metal ions - Gao_2023_Anal.Bioanal.Chem__
Author(s) : Gao L , Chen R , Li H , Xu D , Zheng D
Ref : Anal Bioanal Chem , : , 2023
Abstract : A novel time-resolved fluorescence nanoprobe (PBMO, PLNR-BSA-Mn(2+)-OPD) is fabricated for the label-free determination of acetylcholinesterase (AChE). The ZnGeO:Mn persistent luminescence nanorod (PLNR) and Mn(II) are, respectively, exploited as the signal molecule and quencher to construct the PBMO nanopobe using bovine serum albumin (BSA) as the surface-modified shell and o-phenylenediamine (OPD) as the reducing agent. In the presence of H(2)O(2), the persistent luminescence of PBMO at 530 nm is enhanced remarkably within 30 s due to the oxidation of Mn(II). H(2)O(2) can react with thiocholine (TCh), which is produced through the enzymatic degradation of acetylcholine (ATCh) by AChE. The PBMO nanoprobe is successfully applied to the determination of AChE in the linear range of 0.08-10 U L(-1), with a detection limit of 0.03 U L(-1) (3sigma/s). The practicability of this PBMO nanoprobe is confirmed by accurately monitoring AChE contents in human serum samples, giving rise to satisfactory spiking recoveries of 96.2-103.6%.
ESTHER : Gao_2023_Anal.Bioanal.Chem__
PubMedSearch : Gao_2023_Anal.Bioanal.Chem__
PubMedID: 37889311

Title : Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration - Hirakawa_2023_Nat.Genet__
Author(s) : Hirakawa H , Gao L , Tavakol DN , Vunjak-Novakovic G , Ding L
Ref : Nat Genet , : , 2023
Abstract : Hematopoietic stem cells (HSCs) regenerate after myeloablation, a procedure that adversely disrupts the bone marrow and drives leptin receptor-expressing cells, a key niche component, to differentiate extensively into adipocytes. Regeneration of the bone marrow niche is associated with the resolution of adipocytes, but the mechanisms remain poorly understood. Using Plin1-creER knock-in mice, we followed the fate of adipocytes in the regenerating niche in vivo. We found that bone marrow adipocytes were highly dynamic and dedifferentiated to leptin receptor-expressing cells during regeneration after myeloablation. Bone marrow adipocytes could give rise to osteolineage cells after skeletal injury. The cellular fate of steady-state bone marrow adipocytes was also plastic. Deletion of adipose triglyceride lipase (Atgl) from bone marrow stromal cells, including adipocytes, obstructed adipocyte dedifferentiation and led to severely compromised regeneration of HSCs as well as impaired B lymphopoiesis after myeloablation, but not in the steady state. Thus, the regeneration of HSCs and their niche depends on the cellular plasticity of bone marrow adipocytes.
ESTHER : Hirakawa_2023_Nat.Genet__
PubMedSearch : Hirakawa_2023_Nat.Genet__
PubMedID: 37857934

Title : The Functional Characterization of Carboxylesterases Involved in the Degradation of Volatile Esters Produced in Strawberry Fruits - Zhang_2022_Int.J.Mol.Sci_24_383
Author(s) : Zhang L , Zhou K , Wang M , Li R , Dai X , Liu Y , Jiang X , Xia T , Gao L
Ref : Int J Mol Sci , 24 :383 , 2022
Abstract : Volatile ester compounds are important contributors to the flavor of strawberry, which affect consumer preference. Here, the GC-MS results showed that volatile esters are the basic aroma components of strawberry, banana, apple, pear, and peach, and the volatile esters were significantly accumulated with the maturation of strawberry fruits. The main purpose of this study is to discuss the relationship between carboxylesterases (CXEs) and the accumulation of volatile ester components in strawberries. FaCXE2 and FaCXE3 were found to have the activity of hydrolyzing hexyl acetate, Z-3-hexenyl acetate, and E-2-hexenyl acetate to the corresponding alcohols. The enzyme kinetics results showed that FaCXE3 had the higher affinity for hexyl acetate, E-2-hexenyl acetate, and Z-3-hexenyl acetate compared with FaCXE2. The volatile esters were mainly accumulated at the maturity stages in strawberry fruits, less at the early stages, and the least during the following maturation stages. The expression of FaCXE2 gradually increased with fruit ripening and the expression level of FaCXE3 showed a decreasing trend, which suggested the complexity of the true function of CXEs. The transient expression of FaCXE2 and FaCXE3 genes in strawberry fruits resulted in a significantly decreased content of volatile esters, such as Z-3-hexenyl acetate, methyl hexanoate, methyl butyrate, and other volatile esters. Taken together, FaCXE2 and FaCXE3 are indeed involved in the regulation of the synthesis and degradation of strawberry volatile esters.
ESTHER : Zhang_2022_Int.J.Mol.Sci_24_383
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_24_383
PubMedID: 36613824
Gene_locus related to this paper: frave-FanCXE17 , frave-FanCXE19 , frave-FanCXE3 , frave-FanCXE2 , fraan-FaTA

Title : Emerging role of carboxylesterases in nonalcoholic fatty liver disease - Liu_2022_Biochem.Pharmacol__115250
Author(s) : Liu J , Yao B , Gao L , Zhang Y , Huang S , Wang X
Ref : Biochemical Pharmacology , :115250 , 2022
Abstract : Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a global public health problem. Carboxylesterases (CESs), as potential influencing factors of NAFLD, are very important to improve clinical outcomes. This review aims to deeply understand the role of CESs in the progression of NAFLD and proposes that CESs can be used as potential targets for NAFLD treatment. We first introduced CESs and analyzed the relationship between CESs and hepatic lipid metabolism and inflammation. Then, we further reviewed the regulation of nuclear receptors on CESs, including PXR, CAR, PPARalpha, HNF4alpha and FXR, which may influence the progression of NAFLD. Finally, we evaluated the advantages and disadvantages of existing NAFLD animal models and summarized the application of CES-related animal models in NAFLD research. In general, this review provides an overview of the relationship between CESs and NAFLD and discusses the role and potential value of CESs in the treatment and prevention of NAFLD.
ESTHER : Liu_2022_Biochem.Pharmacol__115250
PubMedSearch : Liu_2022_Biochem.Pharmacol__115250
PubMedID: 36130649

Title : New insights into the function of plant tannase with promiscuous acyltransferase activity - Chen_2022_Plant.J__
Author(s) : Chen Y , Jiang C , Yin S , Zhuang J , Zhao Y , Zhang L , Jiang X , Liu Y , Gao L , Xia T
Ref : Plant J , : , 2022
Abstract : Plant tannases (TAs) or tannin acyl hydrolases, a class of recently reported carboxylesterase (CXE) in tannin-rich plants, are involved in the degalloylation of two important secondary metabolites: flavan-3-ol gallates and hydrolyzable tannins (HTs). In this paper, we have made a new progress on the function of Camellia sinensis (Cs) TA-it is a hydrolase with promiscuous acyltransferase activity in vitro and in vivo experiments and promotes the synthesis of simple galloyl glucoses and flavan-3-ols gallates in plants. We gained the new understanding to the functions of CsTA through enzyme analysis, protein mass spectrometry identification, metabolic analysis of plants by genetic modification. Firstly, CsTA was proved that it is not only a hydrolase but also an acyltransferase. In the two-step covalent catalytic reaction, when CsTA hydrolyzes the galloylated compounds epigallocatechin-3-gallate (EGCG) or 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) into their degalloylated forms, a long-lived Ser159-linked galloyl-enzyme covalent intermediate is also formed. Under nucleophilic attack, the galloyl group on the intermediate is transferred to the nucleophilic acyl acceptors (including water, methanol, flavan-3-ols and simple galloyl glucoses). Then, metabolic analysis suggested that transiently overexpression of TAs in young strawberry fruits, young leaves of tea plants and young leaves of Chinese bayberry actually increased the total content of simple galloyl glucoses and flavan-3-ol gallates. Overall, these findings provide new insights into the promiscuous acyltransferase activity of plant tannase.
ESTHER : Chen_2022_Plant.J__
PubMedSearch : Chen_2022_Plant.J__
PubMedID: 36534122
Gene_locus related to this paper: camsi-CsTA

Title : Insights into acylation mechanisms: co-expression of serine carboxypeptidase-like acyltransferases and their non-catalytic companion paralogs - Yao_2022_Plant.J_111_117
Author(s) : Yao S , Liu Y , Zhuang J , Zhao Y , Dai X , Jiang C , Wang Z , Jiang X , Zhang S , Qian Y , Tai Y , Wang Y , Wang H , Xie DY , Gao L , Xia T
Ref : Plant J , 111 :117 , 2022
Abstract : Serine carboxypeptidase-like acyltransferases (SCPL-ATs) play a vital role in the diversification of plant metabolites. Galloylated flavan-3-ols highly accumulate in tea (Camellia sinensis), grape (Vitis vinifera), and persimmon (Diospyros kaki). To date, the biosynthetic mechanism of these compounds remains unknown. Herein, we report that two SCPL-AT paralogs are involved in galloylation of flavan-3-ols: CsSCPL4, which contains the conserved catalytic triad S-D-H, and CsSCPL5, which has the alternative triad T-D-Y. Integrated data from transgenic plants, recombinant enzymes, and gene mutations showed that CsSCPL4 is a catalytic acyltransferase, while CsSCPL5 is a non-catalytic companion paralog (NCCP). Co-expression of CsSCPL4 and CsSCPL5 is likely responsible for the galloylation. Furthermore, pull-down and co-immunoprecipitation assays showed that CsSCPL4 and CsSCPL5 interact, increasing protein stability and promoting post-translational processing. Moreover, phylogenetic analyses revealed that their homologs co-exist in galloylated flavan-3-ol- or hydrolyzable tannin-rich plant species. Enzymatic assays further revealed the necessity of co-expression of those homologs for acyltransferase activity. Evolution analysis revealed that the mutations of the CsSCPL5 catalytic residues may have taken place about 10 million years ago. These findings show that the co-expression of SCPL-ATs and their NCCPs contributes to the acylation of flavan-3-ols in the plant kingdom.
ESTHER : Yao_2022_Plant.J_111_117
PubMedSearch : Yao_2022_Plant.J_111_117
PubMedID: 35437852
Gene_locus related to this paper: dioka-dkSCPL1 , camsi-SCPL5 , camsi-SCPL4

Title : Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment - Ye_2022_Nanomedicine__102581
Author(s) : Ye Z , Gao L , Cai J , Wang Y , Li Y , Tong S , Yan T , Sun Q , Qi Y , Xu Y , Jiang H , Zhang S , Zhao L , Chen Q
Ref : Nanomedicine , :102581 , 2022
Abstract : Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.
ESTHER : Ye_2022_Nanomedicine__102581
PubMedSearch : Ye_2022_Nanomedicine__102581
PubMedID: 35811067

Title : Role of epoxyeicosatrienoic acids in cardiovascular diseases and cardiotoxicity of drugs - Zhang_2022_Life.Sci_310_121122
Author(s) : Zhang Y , Gao L , Yao B , Huang S , Liu J , Liu Z , Wang X
Ref : Life Sciences , 310 :121122 , 2022
Abstract : Epoxyeicosatrienoic acids (EETs) are important endogenous substances that affect heart function in human body. Animal models of cytochrome P450 (CYP) and soluble epoxide hydrolase (sEH) related cardiovascular diseases (CVD) have revealed the physiological effects of EETs, mainly including vascular function regulation, angiogenesis, myocardial fibrosis, myocardial hypertrophy, and cardiovascular inflammation. At the same time, clinical studies have found that most of the substrates and inhibitors of CYP2J2 affect the content of EETs, resulting in cardiotoxicity of drugs. Therefore, the regulation of CYP and sEH enzymes on EETs points out the direction for exploring EET-mediated cardiac protection. The metabolic pathway of EETs is not only an important target for the development of new drugs for CVD but also an important factor in preventing drug cardiotoxicity. The development and clinical application of sEH inhibitors and EETs analogues provide broad prospects for the treatment of CVD.
ESTHER : Zhang_2022_Life.Sci_310_121122
PubMedSearch : Zhang_2022_Life.Sci_310_121122
PubMedID: 36309225

Title : Identification and Characterization of Two Novel Compounds: Heterozygous Variants of Lipoprotein Lipase in Two Pedigrees With Type I Hyperlipoproteinemia - Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
Author(s) : Wang S , Cheng Y , Shi Y , Zhao W , Gao L , Fang L , Jin X , Han X , Sun Q , Li G , Zhao J , Xu C
Ref : Front Endocrinol (Lausanne) , 13 :874608 , 2022
Abstract : BACKGROUND: Type I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis. OBJECTIVE: This study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia. METHODS: We conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium. RESULTS: Proband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 +/- 9.46% (p<0.01) and 54.60 +/- 9.03% (p<0.01), respectively, compared with the control. In vitro studies showed a substantial reduction in the expression or enzyme activity of LPL in the LPL variants. CONCLUSIONS: Two novel compound heterozygous variants of LPL induced defects in the expression and function of LPL and caused type I hyperlipoproteinemia. The functional characterization of these variants was in keeping with the postulated LPL mutant activity.
ESTHER : Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
PubMedSearch : Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
PubMedID: 35923617
Gene_locus related to this paper: human-LPL

Title : A novel method of subxiphoid video-assisted thoracic surgery for thymectomy - Gao_2021_Ann.Transl.Med_9_1339
Author(s) : Gao L , Lu J , Shen Z , Chen H , Kang M
Ref : Ann Transl Med , 9 :1339 , 2021
Abstract : BACKGROUND: With advances in thoracoscopic surgical instruments and techniques, subxiphoid video-assisted thoracic surgery (S-VATS) has become the main approach for anterior mediastinal tumor resection under thoracoscopy. However, the drawbacks of S-VATS, including it being a relatively unfixed surgical procedure, make it complicated and difficult for unexperienced surgeons to master. METHODS: This study retrospectively reviewed and analyzed consecutive patients with anterior mediastinal tumor or myasthenia gravis (MG) who underwent S-VATS at the Fujian Medical University Union Hospital, China, between March 2015 and April 2019.Patients were divided into the conventional group and the "four-zone one-way" group. Intraoperative and postoperative variables were compared between the groups. Cumulative sum (CUSUM) analysis was applied to determine the operation time (OT)-learning curve of the S-VATS "four-zone one-way" method. RESULTS: A total of 82 patients were included in this analysis, of which, 40 patients underwent the conventional method of S-VATS and 42 patients underwent the "four-zone one-way" method. Patients in the "four-zone one-way" group had significantly shorter OT (138.50+/-29.43 and 118.00+/-28.18 minutes, respectively; P=0.002) and significantly less blood loss (36.00+/-20.16 and 23.92+/-14.96 mL, respectively; P=0.003) compared with patients in the conventional group. Our data indicated that there was no difference of the efficacy of MG treatment between the 2 groups. The difference in the preoperative and postoperative quantitative MG scoring system score (QMG-score) and the dose reduction of cholinesterase inhibitors was comparable between patients in the 2 groups. According to the CUSUM analysis curve, after a steady improvement over phase I (cases 1-12 for the traditional method and cases 1-5 for the "four-zone one-way" method), the surgical procedure could be mastered. Phase III occurred after case 26 in the traditional group and case 28 in the "four-zone one-way" group, and is characterized by rapid improvements. CONCLUSIONS: Compared with the conventional method of S-VATS, the "four-zone one-way" method significantly decreased OT and estimated blood loss. These results demonstrated the feasibility and safety of the "four-zone one-way" method of S-VATS.
ESTHER : Gao_2021_Ann.Transl.Med_9_1339
PubMedSearch : Gao_2021_Ann.Transl.Med_9_1339
PubMedID: 34532476

Title : Nutritional Status and Body Composition in Wilson Disease: A Cross-Sectional Study From China - Geng_2021_Front.Nutr_8_790520
Author(s) : Geng H , Wang S , Jin Y , Cheng N , Song B , Shu S , Li B , Han Y , Gao L , Ding Z , Xu Y , Wang X , Ma Z , Sun Y
Ref : Front Nutr , 8 :790520 , 2021
Abstract : Background: Abnormal nutritional status is frequently seen in patients with chronic diseases. To date, no study has investigated the detailed characteristics of abnormal nutritional status among Wilson's disease (WD) patients in the Chinese cohort. This study aimed to describe the nutritional status of WD patients, with a particular focus on the differences between patients with different phenotypes. Methods: The study subjects comprised 119 healthy controls, 129 inpatients (hepatic subtype, n = 34; neurological subtype, n = 95) who were being treated at the affiliated hospital of the Institute of Neurology, Anhui University of Chinese Medicine. All of the subjects were assessed for body composition by using bioelectrical impedance analysis. All WD patients received anthropometry, nutritional risk screening 2002 (NRS2002), and laboratory test (hemocyte and serum biomarkers) additionally. Results: Compared with healthy controls, the fat mass and rate of total body and trunk were significantly higher in WD patients (P < 0.001), the muscle and skeletal muscle mass of total body and trunk were significantly lower in WD patients (P < 0.001). Compared with hepatic subtype patients, the fat mass and rate of total body, trunk, and limbs were significantly lower in neurological subtype patients (P<0.01); while there were no significant differences in muscle and skeletal muscle between these two subtypes. The overall prevalence of abnormal nutritional status in WD patients was 43.41% (56/129). The prevalence of high-nutritional risk and overweight in WD patients was 17.83% (23 of 129) and 25.58% (33 of 129), respectively. Compare with patients with high nutritional risk, macro platelet ratio, alkaline phosphatase, the basal metabolic rate (p < 0.05), creatinine, trunk fat rate (p < 0.01) and appendicular skeletal muscle mass (p < 0.001) were significantly higher in patients without nutritional risk (p < 0.001). Patients with a high nutritional risk tend to have a lower cholinesterase concentration (x (2) = 4.227, p < 0.05). Conclusion: Both patients with H-subtype and N-subtype are prone to have an abnormal nutritional status. Longitudinal studies are required to investigate if nutritional status and body composition could reflect prognosis in WD patients, and which of these body composition indexes contribute to malnutrition and worse prognosis.
ESTHER : Geng_2021_Front.Nutr_8_790520
PubMedSearch : Geng_2021_Front.Nutr_8_790520
PubMedID: 35036410

Title : Discovery and characterization of tannase genes in plants: roles in hydrolysis of tannins - Dai_2020_New.Phytol_226_1104
Author(s) : Dai X , Liu Y , Zhuang J , Yao S , Liu L , Jiang X , Zhou K , Wang Y , Xie D , Bennetzen JL , Gao L , Xia T
Ref : New Phytol , 226 :1104 , 2020
Abstract : Plant tannins, including condensed tannins (CTs) and hydrolyzable tannins (HTs), are widely distributed in the plant kingdom. To date, tannase (TA) - is a type of tannin acyl-hydrolase hydrolyzing HTs, CT monomer gallates and depsides - has been reported in microbes only. Whether plants express TA remains unknown. Herein, we report plant TA genes. A native Camellia sinensis TA (CsTA) is identified from leaves. Six TAs are cloned from tea, strawberry (Fragariasxsananassa, Fa) and four other crops. Biochemical analysis shows that the native CsTA and six recombinant TAs hydrolyze tannin compounds, depsides and phenolic glycosides. Transcriptional and metabolic analyses reveal that the expression of CsTA is oppositely associated with the accumulation of galloylated catechins. Moreover, the transient overexpression and RNA interference of FaTA are positively associated with the accumulation of ellagitannins in strawberry fruit. Phylogenetic analysis across different kingdoms shows that 29 plant TA homologs are clustered as a plant-specific TA clade in class I carboxylesterases. Further analysis across the angiosperms reveals that these TA genes are dispersed in tannin-rich plants, which share a single phylogenetic origin c. 120 million yr ago. Plant TA is discovered for the first time in the plant kingdom and is shown to be valuable to improve tannin compositions in plants.
ESTHER : Dai_2020_New.Phytol_226_1104
PubMedSearch : Dai_2020_New.Phytol_226_1104
PubMedID: 32061142
Gene_locus related to this paper: camsi-a0a5b9g8c2 , jugre-JrTA , fraan-FaTA , vitvi-VvTA , citcl-CcTA , dioka-DkTA , camsi-CsTA

Title : Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis - Tu_2020_Nat.Commun_11_971
Author(s) : Tu L , Su P , Zhang Z , Gao L , Wang J , Hu T , Zhou J , Zhang Y , Zhao Y , Liu Y , Song Y , Tong Y , Lu Y , Yang J , Xu C , Jia M , Peters RJ , Huang L , Gao W
Ref : Nat Commun , 11 :971 , 2020
Abstract : Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
ESTHER : Tu_2020_Nat.Commun_11_971
PubMedSearch : Tu_2020_Nat.Commun_11_971
PubMedID: 32080175
Gene_locus related to this paper: triwf-a0a7j7c8l4

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : The Herb-Drug Interaction of Clopidogrel and Xuesaitong Dispersible Tablet by Modulation of the Pharmacodynamics and Liver Carboxylesterase 1A Metabolism - Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989
Author(s) : Ma S , Dai G , Bi X , Gong M , Miao C , Chen H , Gao L , Zhao W , Liu T , Zhang N
Ref : Evid Based Complement Alternat Med , 2018 :5651989 , 2018
Abstract : Objective: Clopidogrel and Xuesaitong dispersible tablet (XST) have been clinically proven to be effective for treating cardiocerebrovascular disease. The present study was to investigate the herb-drug interaction of Clopidogrel and XST by modulation of the pharmacodynamics and liver Carboxylesterase 1A(CES1A) metabolism. Methods: 30 male SD rats were randomly divided into a control group (equal volumes of saline, 6 rats for mRNA analysis), a clopidogrel group (clopidogrel with dose 30 mg/kg), and a combination group (clopidogrel and XST, with dose 30 and 50 mg/kg respectively, each group continuous administration once daily for 30 days). The clopidogrel and combination group comprised 12 rats, with 6 designated for mRNA analysis and 6 for the pharmacokinetic study. The 2-bromo-3'-methoxyacetophenone- (MPB-) derivatized clopidogrel active thiol metabolite (CAMD) was measured by UHPLC-MS/MS for pharmacokinetics (n=6). The expression of CES1A mRNA was examined with real-time RT-PCR (n=6). Molecular simulation was used to investigate the inhibition effect of XST on the CES1A protein. The CAMD pharmacodynamics and CES1A metabolism were investigated to evaluated the herb-drug interaction. Results: Clopidogrel and XST coadministration appreciably increased the Cmax, AUC, and MRT of CAMD. However, the expression of CES1A mRNA was decreased accordingly. It also indicated that the bioactive components in XST had good interaction with the CES1A metabolism target by molecular simulation. The animal study indicated that clopidogrel and XST coadministration produced significant herb-drug interactions at active CAMD pharmacokinetic and CES1A metabolic enzyme aspect. Conclusion: 30-days dose of coadministration altered hepatic CES1A protein and resulted in reduced plasma levels of active CAMD. both the decreased CES1A mRNA expression and the inhibition on the protein were due to the combination of XST, which accordingly upregulated the pharmacokinetics of plasma active CAMD.
ESTHER : Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989
PubMedSearch : Ma_2018_Evid.Based.Complement.Alternat.Med_2018_5651989
PubMedID: 30498515

Title : Spatial-temporal expression of NDRG2 in brain tissues in a rat model of intracerebral hemorrhage: A pilot study - Gao_2018_Neurosci.Lett_662_356
Author(s) : Gao L , Li X , Li H , Li J , Shen H , Chen G
Ref : Neuroscience Letters , 662 :356 , 2018
Abstract : N-myc downstream regulated gene 2 (NDRG2) was a member of the N-myc down regulated gene family which belongs to the alpha/beta hydrolase superfamily and played important roles in cell death. To date, the expression and effects of NDRG2 in brain after intracerebral hemorrhage (ICH) are unclear. In this study, we investigated the spatial-temporal expression of NDRG2 in brain tissues in a rat model of ICH. The expression levels of NDRG2 were tested in 3h, 6h, 12h, 24h, 48h, 72h, and 7d after ICH by western blot analysis. The results showed that the NDRG2 levels were increased and peaked at 24h after ICH, and then declined subsequently. Meanwhile, we also examined the NDRG2 cellular localization in brain tissues by immunofluorescence analysis with NeuN and GFAP (biomarker of neuron and astrocytes respectively). The results demonstrated that NDRG2 was mainly expressed in astrocytes, but not neurons, after ICH. Additionally, the results of double staining indicated that the rate of NDRG2- and TUNEL -positive cells was significantly higher in the brain tissues in rats after ICH. The roles of NDRG2 in ICH needed further investigation and inhibiting the expression of NDRG2 may have potential therapeutic effects in ICH.
ESTHER : Gao_2018_Neurosci.Lett_662_356
PubMedSearch : Gao_2018_Neurosci.Lett_662_356
PubMedID: 29037792

Title : The Aegilops tauschii genome reveals multiple impacts of transposons - Zhao_2017_Nat.Plants_3_946
Author(s) : Zhao G , Zou C , Li K , Wang K , Li T , Gao L , Zhang X , Wang H , Yang Z , Liu X , Jiang W , Mao L , Kong X , Jiao Y , Jia J
Ref : Nat Plants , 3 :946 , 2017
Abstract : Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time.
ESTHER : Zhao_2017_Nat.Plants_3_946
PubMedSearch : Zhao_2017_Nat.Plants_3_946
PubMedID: 29158546
Gene_locus related to this paper: horvv-m0utz9 , wheat-a0a3b6c2m6 , wheat-a0a3b5zwb6 , wheat-a0a3b6bzs8 , wheat-a0a1d5zte7 , wheat-a0a1d5uwn5

Title : The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice - Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
Author(s) : Xu P , Wang K , Lu C , Dong L , Gao L , Yan M , Aibai S , Yang Y , Liu X
Ref : Evid Based Complement Alternat Med , 2017 :7426538 , 2017
Abstract : Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimer's disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and protected the increased activity of acetylcholinesterase (AChE) and content of malondialdehyde (MDA). Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII), p-CaMKII, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.
ESTHER : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedSearch : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedID: 28529531

Title : The Effect of Butin on the Vitiligo Mouse Model Induced by Hydroquinone - Huo_2017_Phytother.Res_31_740
Author(s) : Huo SX , Wang Q , Liu XM , Ge CH , Gao L , Peng XM , Yan M
Ref : Phytother Res , 31 :740 , 2017
Abstract : Vernonia anthelmintica (L.) Willd has been traditionally used in the treatment of vitiligo in Uyghur medicine. This study used butin, the main component of V. anthelmintica, to study the influence on hydroquinone-induced vitiligo in mice. The animals were randomly divided into six groups: control, model, 8-methoxypsoralen (8-MOP, 4.25 mg/kg), and butin (0.425, 4.25, and 42.5 mg/kg) groups. The number of melanin-containing hair follicles, basal layer melanocytes, melanin-containing epidermal cells, the expression of tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1), the malondialdehyde (MDA), and cholinesterase (CHE) activity in serum were measured. Our results indicated that compared with the model group, the melanin-containing hair follicles, the expression of TYR and TRP-1 increased, the activity of CHE decreased after treatment with 8-MOP and all doses of butin (p < 0.05, p < 0.01), the basal layer melanocytes and melanin-containing epidermal cells increased significantly after treatment with butin 4.25 and 42.5 mg/kg (p < 0.05, p < 0.01), and the MDA activity decreased after using butin 4.25 and 42.5 mg/kg and 8-MOP (p < 0.05, p < 0.01). Our results support the use of butin on vitiligo, and its possible mechanisms may be related to increase the TYR and TRP-1 protein expression and decrease the activity of MDA and CHE in hydroquinone-induced vitiligo model in mice. Copyright (c) 2017 John Wiley & Sons, Ltd.
ESTHER : Huo_2017_Phytother.Res_31_740
PubMedSearch : Huo_2017_Phytother.Res_31_740
PubMedID: 28321929

Title : Lactate Promotes Synthetic Phenotype in Vascular Smooth Muscle Cells - Yang_2017_Circ.Res_121_1251
Author(s) : Yang L , Gao L , Nickel T , Yang J , Zhou J , Gilbertsen A , Geng Z , Johnson C , Young B , Henke C , Gourley GR , Zhang J
Ref : Circulation Research , 121 :1251 , 2017
Abstract : RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood. OBJECTIVE: To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs. METHODS AND RESULTS: Experiments were performed with vSMCs that had been differentiated from human induced pluripotent stem cells and then cultured in glucose-free, lactate-enriched (L(+)) medium or in standard (L(-)) medium. Compared with the L(-) medium, the L(+) medium was associated with significant increases in synthetic vSMC marker expression, proliferation, and migration and with significant declines in contractile and apoptotic activity. Furthermore, these changes were accompanied by increases in the expression of monocarboxylic acid transporters and were generally attenuated both by the blockade of monocarboxylic acid transporter activity and by transfection with iRNA for NDRG (N-myc downstream regulated gene). Proteomics, biomarker, and pathway analyses suggested that the L(+) medium tended to upregulate the expression of synthetic vSMC markers, the production of extracellular proteins that participate in tissue construction or repair, and the activity of pathways that regulate cell proliferation and migration. Observations in hypoxia-cultured vSMCs were similar to those in L(+)-cultured vSMCs, and assessments in a swine myocardial infarction model suggested that measurements of lactate levels, lactate-dehydrogenase levels, vSMC proliferation, and monocarboxylic acid transporter and NDRG expression were greater in the ischemic zone than in nonischemic tissues. CONCLUSIONS: These results demonstrate for the first time that vSMCs assume a more synthetic phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that link glucose metabolism to vSMC phenotypic switching could play a role in the pathogenesis and treatment of cardiovascular disease.
ESTHER : Yang_2017_Circ.Res_121_1251
PubMedSearch : Yang_2017_Circ.Res_121_1251
PubMedID: 29021296

Title : Protective effect of lavender oil on scopolamine induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells - Xu_2016_J.Ethnopharmacol_193_408
Author(s) : Xu P , Wang K , Lu C , Dong L , Gao L , Yan M , Aibai S , Liu X
Ref : J Ethnopharmacol , 193 :408 , 2016
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Lavender essential oil (LO), an aromatic liquid extracted from Lavandula angustifolia Mill., has been traditionally used in the treatments of many nervous system diseases, and recently LO also reported to be effective for the Alzheimer's disease (AD). AIM OF THE STUDY: The improvement effect of lavender oil (LO) on the scopolamine-induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells have been evaluated. The relevant mechanism was also researched from the perspective of antioxidant effect and cholinergic system modulation. MATERIALS AND
METHODS: Cognitive deficits were induced in C57BL/6J mice treated with scopolamine (1mg/kg, i.p.) and were assessed by Morris water maze (MWM) and step-through passive avoidance tests. Then their hippocampus were removed for biochemical assays (acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA)). In vitro, the cytotoxicity were induced by 4h exposure to H2O2 in PC12 and evaluated by cell viability (MTT), lactate dehydrogenase (LDH) level, nitric oxide (NO) release, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP).
RESULTS: The results demonstrated that LO (100mg/kg) could improve the cognitive performance of scopolamine induced mice in behavioral tests. Meanwhile, it significantly decreased the AChE activity, MDA level, and increase SOD and GPX activities of the model. Moreover, LO (12mug/mL) protected PC12 cells from H2O2 induced cytotoxicity by reducing LDH, NO release, intracellular ROS accumulation and MMP loss.
CONCLUSIONS: It was suggested that LO could show neuroprotective effect in AD model in vivo (scopolamine-treated mice) and in vitro (H2O2 induced PC12 cells) via modulating oxidative stress and AChE activity.
ESTHER : Xu_2016_J.Ethnopharmacol_193_408
PubMedSearch : Xu_2016_J.Ethnopharmacol_193_408
PubMedID: 27558947

Title : Benzoate fraction from Gentiana rigescens Franch alleviates scopolamine-induced impaired memory in mice model in vivo - Li_2016_J.Ethnopharmacol_193_107
Author(s) : Li J , Gao L , Sun K , Xiao D , Li W , Xiang L , Qi J
Ref : J Ethnopharmacol , 193 :107 , 2016
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: G. rigescens Franch (Long Dan Cao in Chinese) is a well-known TCM herb. It is clinically used with other drugs for the treatment of brain diseases such as epilepsy, postherpetic neuralgia in China. AIM OF STUDY: In our previous study, the 11 dihydroxybenzoates compounds with NGF mimicking activity from G. rigescens Franch were found. In the present study, the neurogenesis and neuroprotection of a mixture of benzoates ( n-GS) were investigated in animal level. MATERIALS AND
METHODS: The NGF mimicking activity of n-GS from G. rigescens Franch was examined in PC12 cells. The neurogenesis effects of n-GS were investigated in ICR mice with 5-bromo-2-deoxyuridine (BrdU) and neuronal neclei (NeuN) double immunostaining. Furthermore, the neuroprotection effects of n-GS on the memory in a scopolamine (SCO)-induced mouse model were evaluated with animal behavior tests.
RESULTS: The NGF-mimicking function and neurogenesis of n-GS were observed in PC12 cells and in normal mice. Subsequently, we investigated the effects of n-GS on the memory in a SCO-induced mouse model. In Y-maze test, SCO significantly lowered the alternation. This finding was reversed by n-GS and donepezil (DONE). SCO significantly impaired the mice's performance in novel object recognition (NOR) and Morris water maze (MWM) tests. The time spent to explore the novel object was longer in the n-GS- and DONE-treated groups than in the SCO control group. In the MWM test, the escape latency of n-GS- and DONE-treated groups was shorter than that of the SCO control group. Mechanism study showed that SCO significantly reduced superoxide dismutase (SOD) but increased the activities of acetylcholinesterase (AChE) and the levels of malondialdehyde (MDA) in the hippocampus and cerebral cortex, which all can be improved by n-GS and DONE. Additionally, the phosphorylation of type 1 insulin-like growth factor (IGF-1) receptor, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding (CREB) protein in the hippocampus was significantly up-regulated in the treatment group compared with that in the SCO group.
CONCLUSIONS: n-GS could alleviate impaired memory of the SCO-induced mice model by inhibiting AChE activity and oxidative stress, and regulating the IGF-1R/ERK signaling pathway.
ESTHER : Li_2016_J.Ethnopharmacol_193_107
PubMedSearch : Li_2016_J.Ethnopharmacol_193_107
PubMedID: 27492328

Title : Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations - Fang_2016_Chem.Biol.Drug.Des_87_649
Author(s) : Fang J , Pang X , Wu P , Yan R , Gao L , Li C , Lian W , Wang Q , Liu AL , Du GH
Ref : Chemical Biology Drug Des , 87 :649 , 2016
Abstract : A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2) ) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (DeltaEvdw ) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.
ESTHER : Fang_2016_Chem.Biol.Drug.Des_87_649
PubMedSearch : Fang_2016_Chem.Biol.Drug.Des_87_649
PubMedID: 26648584

Title : Design of hyperthermophilic lipase chimeras by key motif-directed recombination - Zhou_2015_Chembiochem_16_455
Author(s) : Zhou X , Gao L , Yang G , Liu D , Bai A , Li B , Deng Z , Feng Y
Ref : Chembiochem , 16 :455 , 2015
Abstract : Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif psi loop in the alpha/beta-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program. To obtain thermostable lipase-like enzymes, two chimeras were engineered at the key motif regions through recombination of domains from a mesophilic lipase and a hyperthermophilic esterase/peptidase with amino acid identity less than 21 %. The chimeras retained the desirable substrate preference of their mesophilic parent and exhibited more than 100-fold increased thermostability at 50 degrees C. Through site-directed mutation, we further improved activity of the chimera by 4.6-fold. The recombination strategy presented here enables the creation of novel catalysts.
ESTHER : Zhou_2015_Chembiochem_16_455
PubMedSearch : Zhou_2015_Chembiochem_16_455
PubMedID: 25530200

Title : Biodegradation and Mineralization of Polystyrene by Plastic-Eating Mealworms: Part 1. Chemical and Physical Characterization and Isotopic Tests - Yang_2015_Environ.Sci.Technol_49_12080
Author(s) : Yang Y , Yang J , Wu WM , Zhao J , Song Y , Gao L , Yang R , Jiang L
Ref : Environ Sci Technol , 49 :12080 , 2015
Abstract : Polystyrene (PS) is generally considered to be durable and resistant to biodegradation. Mealworms (the larvae of Tenebrio molitor Linnaeus) from different sources chew and eat Styrofoam, a common PS product. The Styrofoam was efficiently degraded in the larval gut within a retention time of less than 24 h. Fed with Styrofoam as the sole diet, the larvae lived as well as those fed with a normal diet (bran) over a period of 1 month. The analysis of fecula egested from Styrofoam-feeding larvae, using gel permeation chromatography (GPC), solid-state (13)C cross-polarization/magic angle spinning nuclear magnetic resonance (CP/MAS NMR) spectroscopy, and thermogravimetric Fourier transform infrared (TG-FTIR) spectroscopy, substantiated that cleavage/depolymerization of long-chain PS molecules and the formation of depolymerized metabolites occurred in the larval gut. Within a 16 day test period, 47.7% of the ingested Styrofoam carbon was converted into CO2 and the residue (ca. 49.2%) was egested as fecula with a limited fraction incorporated into biomass (ca. 0.5%). Tests with alpha (13)C- or beta (13)C-labeled PS confirmed that the (13)C-labeled PS was mineralized to (13)CO2 and incorporated into lipids. The discovery of the rapid biodegradation of PS in the larval gut reveals a new fate for plastic waste in the environment.
ESTHER : Yang_2015_Environ.Sci.Technol_49_12080
PubMedSearch : Yang_2015_Environ.Sci.Technol_49_12080
PubMedID: 26390034

Title : Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication - Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
Author(s) : Yang K , Tian Z , Chen C , Luo L , Zhao B , Wang Z , Yu L , Li Y , Sun Y , Li W , Chen Y , Zhang Y , Ai D , Zhao J , Shang C , Ma Y , Wu B , Wang M , Gao L , Sun D , Zhang P , Guo F , Wang W , Wang J , Varshney RK , Ling HQ , Wan P
Ref : Proc Natl Acad Sci U S A , 112 :13213 , 2015
Abstract : Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean.
ESTHER : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedSearch : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedID: 26460024
Gene_locus related to this paper: phaan-a0a0l9ttq5 , phaan-a0a0l9vh69 , phaan-a0a0l9vh89 , phaan-a0a0s3tc53 , vigrr-a0a1s3v914 , phaan-a0a0s3s998 , phaan-a0a0s3siv8 , phaan-a0a0l9uys5 , phaan-a0a0s3rp07 , phaan-a0a0s3rbq0 , vigrr-a0a1s3tul4 , phaan-a0a0s3smk7 , phaan-a0a0s3slm9 , phaan-a0a0l9ujf5 , phaan-a0a0l9til9 , phaan-a0a0l9uqr2 , phaan-a0a0l9v1m8 , phaan-a0a0l9uc60 , phaan-a0a0l9ucr8

Title : Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation - Fang_2014_Acta.Pharm.Sin.B_4_430
Author(s) : Fang J , Wu P , Yang R , Gao L , Li C , Wang D , Wu S , Liu AL , Du GH
Ref : Acta Pharm Sin B , 4 :430 , 2014
Abstract : In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (DeltaE ele+DeltaG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.
ESTHER : Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedSearch : Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedID: 26579414

Title : The effects of galangin on a mouse model of vitiligo induced by hydroquinone - Huo_2014_Phytother.Res_28_1533
Author(s) : Huo SX , Liu XM , Ge CH , Gao L , Peng XM , Zhao PP , Yan M
Ref : Phytother Res , 28 :1533 , 2014
Abstract : Galangin, the main active component of Alpinia officinarum Hance, was tested in a mouse model of vitiligo induced in C57BL/6 mice by the topical application of 2 mL of 2.5% hydroquinone daily to shaved areas (2 x 2 cm) of dorsal skin for 60 days. Thirty days after the final application of hydroquinone, galangin (0.425, and 4.25 mg/kg) was administered orally for 30 days. The hair colour darkened when it grew back after treatment, and histological analysis showed that the number of melanin-containing hair follicles had increased after treatment with all doses of galangin groups and 8-methoxypsoralen (8-MOP, the positive control) compared with the untreated vitiligo group (p < 0.05). The number of skin basal layer melanocytes and melanin-containing epidermal cells had also increased significantly with the application of 4.25 mg/kg of galangin. The concentration of tyrosinase (TYR) in serum was found to have increased, whereas the content of malondialdehyde and the activity of cholinesterase had decreased after treatment with all doses of galangin and 8-MOP, compared with control (p < 0.05). The expression of TYR protein in treated areas of skin also increased with the application of 4.25 mg/kg galangin and 8-MOP. In conclusion, the results showed that galangin was able to improve vitiligo induced by hydroquinone in mice, with the activity related to concentrations of TYR, expression of TYR protein, activity of malondialdehyde and content of cholinesterase. Galangin may therefore be a potential candidate for the treatment of vitiligo, subject to further investigation. Copyright (c) 2014 John Wiley & Sons, Ltd.
ESTHER : Huo_2014_Phytother.Res_28_1533
PubMedSearch : Huo_2014_Phytother.Res_28_1533
PubMedID: 24820380

Title : Predictions of BCHE Inhibitors Using Support Vector Machine and Naive Bayesian Classification Techniques in Drug Discovery - Fang_2013_J.Chem.Inf.Model_53_3009
Author(s) : Fang J , Yang R , Gao L , Zhou D , Yang S , Liu AL , Du GH
Ref : J Chem Inf Model , 53 :3009 , 2013
Abstract : Butyrylcholinesterase (BCHE, EC is an important pharmacological target for Alzheimer's disease (AD) treatment. However, the currently available BCHE inhibitor screening assays are expensive, labor-intensive, and compound-dependent. It is necessary to develop robust in silico methods to predict the activities of BCHE inhibitors for the lead identification. In this investigation, support vector machine (SVM) models and naive Bayesian models were built to discriminate BCHE inhibitors (BCHEIs) from the noninhibitors. Each molecule was initially represented in 1870 structural descriptors (1235 from ADRIANA.Code, 334 from MOE, and 301 from Discovery studio). Correlation analysis and stepwise variable selection method were applied to figure out activity-related descriptors for prediction models. Additionally, structural fingerprint descriptors were added to improve the predictive ability of models, which were measured by cross-validation, a test set validation with 1001 compounds and an external test set validation with 317 diverse chemicals. The best two models gave Matthews correlation coefficient of 0.9551 and 0.9550 for the test set and 0.9132 and 0.9221 for the external test set. To demonstrate the practical applicability of the models in virtual screening, we screened an in-house data set with 3601 compounds, and 30 compounds were selected for further bioactivity assay. The assay results showed that 10 out of 30 compounds exerted significant BCHE inhibitory activities with IC50 values ranging from 0.32 to 22.22 muM, at which three new scaffolds as BCHE inhibitors were identified for the first time. To our best knowledge, this is the first report on BCHE inhibitors using machine learning approaches. The models generated from SVM and naive Bayesian approaches successfully predicted BCHE inhibitors. The study proved the feasibility of a new method for predicting bioactivities of ligands and discovering novel lead compounds.
ESTHER : Fang_2013_J.Chem.Inf.Model_53_3009
PubMedSearch : Fang_2013_J.Chem.Inf.Model_53_3009
PubMedID: 24144102

Title : Purification and characterization of a novel galloyltransferase involved in catechin galloylation in the tea plant (Camellia sinensis) - Liu_2012_J.Biol.Chem_287_44406
Author(s) : Liu Y , Gao L , Liu L , Yang Q , Lu Z , Nie Z , Wang Y , Xia T
Ref : Journal of Biological Chemistry , 287 :44406 , 2012
Abstract : Catechins (flavan-3-ols), the most important secondary metabolites in the tea plant, have positive effects on human health and are crucial in defense against pathogens of the tea plant. The aim of this study was to elucidate the biosynthetic pathway of galloylated catechins in the tea plant. The results suggested that galloylated catechins were biosynthesized via 1-O-glucose ester-dependent two-step reactions by acyltransferases, which involved two enzymes, UDP-glucose:galloyl-1-O-beta-D-glucosyltransferase (UGGT) and a newly discovered enzyme, epicatechin:1-O-galloyl-beta-D-glucose O-galloyltransferase (ECGT). In the first reaction, the galloylated acyl donor beta-glucogallin was biosynthesized by UGGT from gallic acid and uridine diphosphate glucose. In the second reaction, galloylated catechins were produced by ECGT catalysis from beta-glucogallin and 2,3-cis-flavan-3-ol. 2,3-cis-Flavan-3-ol and 1-O-galloyl-beta-D-glucose were appropriate substrates of ECGT rather than 2,3-trans-flavan-3-ol and 1,2,3,4,6-pentagalloylglucose. Purification by more than 1641-fold to apparent homogeneity yielded ECGT with an estimated molecular mass of 241 to 121 kDa by gel filtration. Enzyme activity and SDS-PAGE analysis indicated that the native ECGT might be a dimer, trimer, or tetramer of 60- and/or 58-kDa monomers, and these monomers represent a heterodimer consisting of pairs of 36- or 34- of and 28-kDa subunits. MALDI-TOF-TOF MS showed that the protein SCPL1199 was identified. Epigallocatechin and epicatechin exhibited higher substrate affinities than beta-glucogallin. ECGT had an optimum temperature of 30 degreesC and maximal reaction rates between pH 4.0 and 6.0. The enzyme reaction was inhibited dramatically by phenylmethylsulfonyl fluoride, HgCl(2), and sodium deoxycholate.
ESTHER : Liu_2012_J.Biol.Chem_287_44406
PubMedSearch : Liu_2012_J.Biol.Chem_287_44406
PubMedID: 23132863
Gene_locus related to this paper: camsi-SCPL13

Title : Alteration of substrate specificities of thermophilic alpha\/beta hydrolases through domain swapping and domain interface optimization - Zhou_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_965
Author(s) : Zhou X , Wang H , Zhang Y , Gao L , Feng Y
Ref : Acta Biochim Biophys Sin (Shanghai) , 44 :965 , 2012
Abstract : Protein domain swapping is an efficient way in protein functional evolution in vivo and also has been proved to be an effective strategy to modify the function of the multi-domain proteins in vitro. To explore the potentials of domain swapping for alteration of the enzyme substrate specificities and the structure-function relationship of the homologous proteins, here we constructed two chimeras from a pair of thermophilic members of the alpha/beta hydrolase superfamily by grafting their functional domains to the conserved alpha/beta hydrolase fold domain: a carboxylesterase from Archaeoglobus fulgidus (AFEST) and an acylpeptide hydrolase from Aeropyrum pernix K1 (apAPH) and explored their activities on hydrolyze p-nitrophenyl esters (pNP) with different acyl chain lengths. We took two approaches to reduce the crossover disruptions when creating the chimeras: chose the residue which involved in the least contacts as the splicing site and optimized the newly formed domain interfaces of the chimeras by site-directed mutations. Characterizations of AAM7 and PAR showed that these chimeras inherited the thermophilic property of both parents. In the aspect of substrate specificity, AAM7 and PAR showed highest activity towards short chain length substrate pNPC4 and middle chain length substrate pNPC8, similar to parent AFEST and apAPH, respectively. These results suggested that the substrate-binding domain is the dominant factor on enzyme substrate specificity, and the optimization of the newly formed domain interface is an important guarantee for successful domain swapping of proteins with low-sequence homology.
ESTHER : Zhou_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_965
PubMedSearch : Zhou_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_965
PubMedID: 23099882

Title : A novel GLP-1 analog, BPI3006, with potent DPP IV resistance and good glucoregulatory effect - Li_2010_Biochem.Biophys.Res.Commun_400_563
Author(s) : Li C , Huan Y , Shen N , Ji L , Sun S , Liu S , Liu Q , Gao L , Tan F , Wang Y , Shen Z
Ref : Biochemical & Biophysical Research Communications , 400 :563 , 2010
Abstract : Glucagon-like peptide-1 (GLP-1) is an incretin hormone that decreases postprandial glycemic excursions by enhancing insulin secretion but with short half-life due to rapid inactivation by enzymatic N-terminal truncation. Therefore, efforts are being made to improve the stability of GLP-1 via modifying its structure or inhibiting dipeptidyl-peptidase IV (DPP IV), which is responsible for its degradation. Here we report a novel GLP-1 analog BPI3006 with -NHCO- of Ala(8) replaced by -CH(CF(3))NH- and features of its metabolic stability, GLP-1 receptor trans-activation and in vivo biological activity. BPI3006 is highly resistant to DPP IV-mediated degradation with 91.1% of parental peptide left after 24h exposure to the enzyme. BPI3006 also effectively activates its target gene promoter through GLP-1 receptor activation by measuring the transiently transfected reporter gene green fluorescence protein (GFP) expression in NIT-1 cells. Furthermore, BPI3006 could well restrain the glycemia variation in fasted normal ICR mice after a single administration followed by an oral glucose loading. In spontaneous type 2 diabetic KKA(y) mice, BPI3006 injected twice daily could significantly improve the oral glucose tolerance and hyperinsulinemia, as well as ameliorate the food and water consumption. In conclusion, BPI3006 has enhanced resistance to DPP IV leading to improved stability, and shows excellent in vivo biological activity. Thus it may be a new candidate for T2DM treatment and its novel modification may provide valuable guidance for the future development of long-acting GLP-1 analogs.
ESTHER : Li_2010_Biochem.Biophys.Res.Commun_400_563
PubMedSearch : Li_2010_Biochem.Biophys.Res.Commun_400_563
PubMedID: 20804731

Title : Isolation and characterization of low-sulphur-tolerant mutants of Arabidopsis - Wu_2010_J.Exp.Bot_61_3407
Author(s) : Wu Y , Zhao Q , Gao L , Yu XM , Fang P , Oliver DJ , Xiang CB
Ref : J Exp Bot , 61 :3407 , 2010
Abstract : Sulphur is an essential element for plant growth and development as well as for defence against biotic and abiotic stresses. Increasing sulphate utilization efficiency (SUE) is an important issue for crop improvement. Little is known about the genetic determinants of sulphate utilization efficiency. No gain-of-function mutants with improved SUE have been reported to date. Here the isolation and characterization of two low-sulphur-tolerant mutants, sue3 and sue4 are reported using a high-throughput genetic screen where a 'sulphur-free' solid medium was devised to give the selection pressure necessary to suppress the growth of the wild-type seedlings. Both mutants showed improved tolerance to low sulphur conditions and well-developed root systems. The mutant phenotype of both sue3 and sue4 was specific to sulphate deficiency and the mutants displayed enhanced tolerance to heavy metal and oxidative stress. Genetic analysis revealed that sue3 was caused by a single recessive nuclear mutation while sue4 was caused by a single dominant nuclear mutation. The recessive locus in sue3 is the previously identified VirE2-interacting Protein 1. The dominant locus in sue4 is a function-unknown locus activated by the four enhancers on the T-DNA. The function of SUE3 and SUE4 in low sulphur tolerance was confirmed either by multiple mutant alleles or by recapitulation analysis. Taken together, our results demonstrate that this genetic screen is a reasonable approach to isolate Arabidopsis mutants with improved low sulphur tolerance and potentially with enhanced sulphate utilization efficiency. The two loci identified in sue3 and sue4 should assist in understanding the molecular mechanisms of low sulphur tolerance.
ESTHER : Wu_2010_J.Exp.Bot_61_3407
PubMedSearch : Wu_2010_J.Exp.Bot_61_3407
PubMedID: 20547563

Title : Glu88 in the non-catalytic domain of acylpeptide hydrolase plays dual roles: charge neutralization for enzymatic activity and formation of salt bridge for thermodynamic stability - Yang_2009_Biochim.Biophys.Acta_1794_94
Author(s) : Yang G , Bai A , Gao L , Zhang Z , Zheng B , Feng Y
Ref : Biochimica & Biophysica Acta , 1794 :94 , 2009
Abstract : Acylpeptide hydrolase of Aeropyrum pernix K1 is composed of a catalytic alpha/beta hydrolase domain and a non-catalytic beta-propeller domain. The Glu88 residue of the propeller domain is highly conserved in the prolyl oligopeptidase family and forms an inter-domain salt bridge with Arg526, a key residue for substrate binding. We have dissected the functions of Glu88 using site-directed mutagenesis, steady-state kinetics analyses, and molecular dynamics simulations. In E88A and E88A/R526K mutants, with a broken inter-domain salt bridge and a positive charge at position 526, catalytic activities for both a peptidase substrate and an esterase substrate were almost abolished. Analysis of the pH dependence of the mutants' reaction kinetics indicates that these mutations lead to changes in the electrostatic environment of the active site, which can be modulated by chloride ions. These findings indicate that the neutralization at position 526 is favorable for the activity of the enzyme, which is also verified by the catalytic behavior of E88A/R526V mutant. All mutants have lower thermodynamic stability than the wild-type. Therefore, Glu88 plays two major roles in the function of the enzyme: neutralizing the positive charge of Arg526, thereby increasing the enzymatic activity, and forming the Glu88-Arg526 salt bridge, thereby stabilizing the protein.
ESTHER : Yang_2009_Biochim.Biophys.Acta_1794_94
PubMedSearch : Yang_2009_Biochim.Biophys.Acta_1794_94
PubMedID: 18930847

Title : Environmental adaptation: genomic analysis of the piezotolerant and psychrotolerant deep-sea iron reducing bacterium Shewanella piezotolerans WP3 - Wang_2008_PLoS.One_3_e1937
Author(s) : Wang F , Wang J , Jian H , Zhang B , Li S , Zeng X , Gao L , Bartlett DH , Yu J , Hu S , Xiao X
Ref : PLoS ONE , 3 :e1937 , 2008
Abstract : Shewanella species are widespread in various environments. Here, the genome sequence of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant iron reducing bacterium from deep-sea sediment was determined with related functional analysis to study its environmental adaptation mechanisms. The genome of WP3 consists of 5,396,476 base pairs (bp) with 4,944 open reading frames (ORFs). It possesses numerous genes or gene clusters which help it to cope with extreme living conditions such as genes for two sets of flagellum systems, structural RNA modification, eicosapentaenoic acid (EPA) biosynthesis and osmolyte transport and synthesis. And WP3 contains 55 open reading frames encoding putative c-type cytochromes which are substantial to its wide environmental adaptation ability. The mtr-omc gene cluster involved in the insoluble metal reduction in the Shewanella genus was identified and compared. The two sets of flagellum systems were found to be differentially regulated under low temperature and high pressure; the lateral flagellum system was found essential for its motility and living at low temperature.
ESTHER : Wang_2008_PLoS.One_3_e1937
PubMedSearch : Wang_2008_PLoS.One_3_e1937
PubMedID: 18398463
Gene_locus related to this paper: shepw-b8ci75 , shepw-b8cib3 , shepw-b8ciu7 , shepw-b8cld5 , shepw-b8cll2 , shepw-b8clm3 , shepw-b8cls4 , shepw-b8ct86 , shepw-b8ctf0 , shepw-b8ctt3 , shepw-b8cuq7 , shepw-b8cuu6 , shepw-b8cuz1 , shepw-b8cvm0 , shepw-b8cqh1 , shepw-b8cgv9 , shepw-b8chj5 , shepw-b8cpv3 , shepw-b8civ4 , shepw-b8cn18

Title : Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on peroxisome proliferator response element pathway - Fan_2006_J.Pharmacol.Sci_100_51
Author(s) : Fan C , Yan J , Qian Y , Wo X , Gao L
Ref : J Pharmacol Sci , 100 :51 , 2006
Abstract : To investigate the possibility that natural medicines affect lipid metabolism by regulating lipoprotein lipase (LPL) expression, a green fluorescent protein (GFP) gene was constructed downstream of the peroxisome proliferator response element (PPRE) and the constructed plasmid was microinjected into Xenopus oocytes to establish a PPRE regulatory reporter system. Using this system, hawthorn flavonoids were quickly selected from a panel of natural medicines and found to up-regulate GFP expression by an effect on PPRE. To confirm the effect of hawthorn flavonoids, we treated mice orally with water (control), hawthorn flavonoids, and pioglitazone and measured the LPL levels in serum, adipose tissue, and muscle by an enzyme-linked immunosorbent assay. The serum LPL levels were no different from the controls after treatment with either hawthorn flavonoids or pioglitazone, but LPL increased significantly in muscular tissues and decreased in adipose tissues. These results demonstrate that hawthorn flavonoids meditate LPL expression in mice with tissue-specific differences. A novel PPRE regulatory report system was established for rapid and effective selection and evaluation of LPL-mediating drugs.
ESTHER : Fan_2006_J.Pharmacol.Sci_100_51
PubMedSearch : Fan_2006_J.Pharmacol.Sci_100_51
PubMedID: 16404131

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Optimization of Serratia marcescens lipase production for enantioselective hydrolysis of 3-phenylglycidic acid ester - Gao_2004_J.Ind.Microbiol.Biotechnol_31_525
Author(s) : Gao L , Xu JH , Li XJ , Liu ZZ
Ref : J Ind Microbiol Biotechnol , 31 :525 , 2004
Abstract : Lipase production and cell growth of Serratia marcescens ECU1010 were optimized in shake flasks, with lipase production being enhanced 9.5-fold (4,780 U/l) compared with the initial activity (500 U/l). Optimal carbon and nitrogen sources were Tween-80 and peptone, and the optimal ratio of Tween-80 to peptone was 1:3. The optimized cultivation conditions were 25 degrees C and pH 6.5. Lipase activity, particularly specific activity, could be improved by decreasing the cultivation temperature from 35 to 25 degrees C. Enzyme stability was significantly improved by simple immobilization with synthetic adsorption resin no. 8244. After five reaction cycles, enzyme activity decreased only very slightly, while enantioselectivity of the preparation remained constant, and the ees (enantiomeric excess of the remaining substrate) achieved in all cases was higher than 97%. The resin-8244-lipase preparation can be used for efficient enantioselective hydrolysis of trans-3-(4'-methoxyphenyl)glycidic acid methyl ester [(+/-)-MPGM], a key intermediate in the synthesis of Diltiazem.
ESTHER : Gao_2004_J.Ind.Microbiol.Biotechnol_31_525
PubMedSearch : Gao_2004_J.Ind.Microbiol.Biotechnol_31_525
PubMedID: 15549608