Shen Z

References (19)

Title : Molecular insight into the enhanced performance of CALB toward PBDF degradation - Ren_2024_Int.J.Biol.Macromol_262_130181
Author(s) : Ren Y , Cheng L , Cheng Z , Liu Y , Li M , Yuan T , Shen Z
Ref : Int J Biol Macromol , 262 :130181 , 2024
Abstract : Poly(butylene diglycolate-co-furandicarboxylate) (PBDF) is a newly developed biodegradable copolyester. Candida antarctica lipase B (CALB) has been identified as an effective catalyst for PBDF degradation. The mechanism is elucidated using a combination of molecular dynamics simulations and quantum chemistry approaches. The findings unveil a four-step catalytic reaction pathway. Furthermore, bond analysis, charge and interaction analysis are conducted to gain a more comprehensive understanding of the PBDF degradation process. Additionally, through the introduction of single-point mutations to crucial residues in CALB's active sites, two mutants, T138I and D134I, are discovered to exhibit improved catalytic efficiency. These significant findings contribute to the advancement of our comprehension concerning the molecular mechanism of underlying copolyesters degradation, while also presenting a novel approach for expediting the degradation rate by the CALB enzyme modification.
ESTHER : Ren_2024_Int.J.Biol.Macromol_262_130181
PubMedSearch : Ren_2024_Int.J.Biol.Macromol_262_130181
PubMedID: 38360240

Title : Identification of genes related to glucose metabolism and analysis of the immune characteristics in Alzheimer's disease - Wang_2023_Brain.Res_1819_148545
Author(s) : Wang Y , Shen Z , Wu H , Yu Z , Wu X , Zhou L , Guo F
Ref : Brain Research , 1819 :148545 , 2023
Abstract : OBJECTIVE: Glucose metabolism plays a crucial role in the progression of Alzheimer's disease (AD). The purpose of this study is to identify genes related to glucose metabolism in AD by bioinformatics, construct an early AD prediction model from the perspective of glucose metabolism, and analyze the characteristics of immune cell infiltration. METHODS: AD-related modules and genes were screened by weighted gene co-expression network analysis (WGCNA). The GO and KEEG enrichment analysis were used to explore the potential biological functions of glucose metabolism related genes (GMRGs) in AD. The Least Absolute Shrinkage Selection Operator (LASSO) method was used to construct an early AD prediction model based on GMRGs. Then, the receiver operating characteristic curve (ROC) and nomogram were introduced to evaluate the effectiveness of this model. Finally, CIBERSORT and single-cell analysis were applied for illustrating the immune characteristics in AD patients. RESULTS: A total of 462 differential expressed genes (DEGs) were obtained between Non-Alzheimer's disease (ND,) and AD groups. The genes in the blue module had the highest correlation with AD by WGCNA analysis. We found 18 intersected genes among DEGs, blue model genes and GMRGs according to the Venn diagram. The GO and KEEG enrichment analysis showed that these 18 genes were mainly involved in the production of metabolites and energy, glycolysis, amino acid biosynthesis and so on. The early AD prediction model including ENO2, TPI1, AEBP1, HERC1, PCSK1, PREPL, SLC25A4, UQCRC2, CHST6, DDIT4, ACSS1 and SUCLA2 was constructed by LASSO analysis. The area under the curve (AUC) of this model in brain tissues was 0.942. Then, we draw the nomogram of this model and the C-index was 0.942. The model was further validated in blood samples and the AUC was 0.644. Immune cell infiltration analysis showed that the proportion of plasma cells, T cells follicular helper and activated NK cells in AD group were significantly lower than ND group, while the proportion of M1 macrophages, neutrophils, T cells CD4 naive and gamma-delta T cells was significantly increased when compared with the ND group. Additionally, the specific GMRGs such as ENO2, DDIT4, and SUCLA2 are significantly correlated with certain immune cells such as plasma cells, follicular helper T cells, and M1 macrophages. Single-cell analysis results suggested that the increased macrophages in AD was associated with the up-regulation of AEBP1, DDIT4 and ACSS1. CONCLUSIONS: The diagnosis model based on the twelve GMRGs has strong predictive ability and can be used as early diagnosis biomarkers for AD. In addition, these GMRGs closely associate with AD development by influencing the glucose metabolism of immune cells.
ESTHER : Wang_2023_Brain.Res_1819_148545
PubMedSearch : Wang_2023_Brain.Res_1819_148545
PubMedID: 37619853

Title : Anoectochilus roxburghii flavonoids extract ameliorated the memory decline and reduced neuron apoptosis via modulating SIRT1 signaling pathway in senescent mice - Zeng_2022_J.Ethnopharmacol__115361
Author(s) : Zeng Z , Chen C , Situ Y , Shen Z , Chen Y , Zhang Z , Tang C , Jiang T
Ref : J Ethnopharmacol , :115361 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (A. roxburghii) is a precious herb and folk medicine in many Asian countries. It has been used traditionally to treat diabetes, etc., and also used as a dietary therapy to delay senescence. AIM OF THE STUDY: This study was to evaluate the neuroprotective effects of A. roxburghii flavonoids extract (ARF) and whether its effects were due to the regulation of SIRT1 signaling pathway in senescent mice and in D-galactose (D-gal) induced aging in SH-SY5Y cells. MATERIALS AND METHODS: 18-month-old mice were randomly divided into senescent model, low-dose ARF, high-dose ARF and vitamin E group. 2-Month-old mice were as a control group. After 8 weeks treatment, Morris water maze (MWM) was performed. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), monoamine oxidase (MAO) and acetylcholinesterase (AChE) in the cortex were determined. Hippocampus morphologic changes were observed with haematoxylin and eosin (H&E), Nissl, senescence-associated-galactosidase (SA-beta-gal) and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining. Apoptosis-related molecular expressions in the hippocampus were performed by western blotting. Furthermore, after stimulated by EX527 (a SIRT1 inhibitor), the SIRT1-dependent neuroprotective effects of ARF were determined by measuring SRIT1 and p53 expression in SH-SY5Y aging cells induced by D-gal. RESULTS: ARF could significantly ameliorated memory decline in senescent mice and reduced the generations of ROS, MDA and the activities of MAO and ACh-E, while increasing SOD activities in the cortex of aging mice. ARF obviously improved hippocampus pathological alterations, increased the number of Nissl bodies, while reducing senescent and apoptotic cells in senescent mice hippocampus. Further, ARF positively regulated SIRT1 expression, and reduced apoptosis-related molecules p53, p21 and Caspase-3 expression, while increasing the ratio of Bcl-2/Bax. In D-gal-induced SH-SY5Y cells, the effects of ARF on SIRT1 and p53, and the ability of scavenging ROS were mostly abolished after incubation with the EX527. CONCLUSIONS: ARF, in a SIRT1-dependent manner, exerted neuroprotection via modulating SIRT1/p53 signaling pathway against memory decline and apoptosis due to age-induced oxidative stress damage in senescent mice.
ESTHER : Zeng_2022_J.Ethnopharmacol__115361
PubMedSearch : Zeng_2022_J.Ethnopharmacol__115361
PubMedID: 35609756

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 : Development of the hidden multifunctional agents for Alzheimer's disease - Huang_2019_Eur.J.Med.Chem_177_247
Author(s) : Huang W , Liang M , Li Q , Zheng X , Zhang C , Wang Q , Tang L , Zhang Z , Wang B , Shen Z
Ref : Eur Journal of Medicinal Chemistry , 177 :247 , 2019
Abstract : Alzheimer's disease (AD) is a chronic, fatal and complex neurodegenerative disorder, which is characterized by cholinergic system dysregulation, metal dyshomeostasis, amyloid-beta (Abeta) aggregation, etc. Therefore in most cases, single-target or single-functional agents are insufficient to achieve the desirable effect against AD. Multi-Target-Directed Ligand (MTDL), which is rationally designed to simultaneously hit multiple targets to improve the pharmacological profiles, has been developed as a promising approach for drug discovery against AD. To identify the multifunctional agents for AD, we developed an innovative method to successfully conceal the metal chelator into acetylcholinesterase (AChE) inhibitor. Briefly, the "hidden" agents first cross the Blood Brain Barrier (BBB) to inhibit the function of AChE, and the metal chelator will then be released via the enzymatic hydrolysis by AChE. Therefore, the AChE inhibitor, in this case, is not only a single-target agent against AD, but also a carrier of the metal chelator. In this study a total of 14 quinoline derivatives were synthesized and biologically evaluated. Both in vitro and in vivo results demonstrated that compound 9b could cross the BBB efficiently, then release 8a, the metabolite of 9b, into brain. In vitro, 9b had a potent AChE inhibitory activity, while 8a displayed a significant metal ion chelating function, therefore in combination, both 9b and 8a exhibited a considerable inhibition of Abeta aggregation, one of the observations that plays important roles in the pathogenesis of AD. The efficacy of 9b against AD was further investigated in both a zebrafish model and two different mice models.
ESTHER : Huang_2019_Eur.J.Med.Chem_177_247
PubMedSearch : Huang_2019_Eur.J.Med.Chem_177_247
PubMedID: 31158742

Title : Protective effects of enzyme degradation extract from Porphyra yezoensis against oxidative stress and brain injury in D-galactose-induced aging mice - Wang_2019_Br.J.Nutr__1
Author(s) : Wang C , Shen Z , Yu J , Yang J , Meng F , Jiang X , Zhu C
Ref : British Journal of Nutrition , :1 , 2019
Abstract : This study investigated the effects of Porphyra yezoensis enzyme degradation extract (PYEDE) on the brain injuries and neurodegenerative diseases due to oxidative stress. We used in vitro antioxidant systems to verify the antioxidant potential of PYEDE. The results indicated that PYEDE alleviated weight loss and organ atrophy, reduced the levels of lipid peroxidation and protein carbonylation, and elevated glutathione (GSH) content in the serum and brains of the D-gal-induced aging model mice. PYEDE also renewed the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total anti-oxidant capability (T-AOC) activities, downregulated the inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) levels, normalized the hippocampal neurons, and modulated multiple neurotransmitter systems by inhibiting the activities of acetylcholinesterase (AchE) and monoamine oxidase (MAO) in the upregulation of acetylcholine (Ach), dopamine (DA) and norepinephrine (NE) levels. Overall, PYEDE is a promising supplement for the alleviation of oxidative stress and age-associated brain diseases.
ESTHER : Wang_2019_Br.J.Nutr__1
PubMedSearch : Wang_2019_Br.J.Nutr__1
PubMedID: 31787131

Title : The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo - Huan_2017_Sci.Rep_7_4351
Author(s) : Huan Y , Jiang Q , Li G , Bai G , Zhou T , Liu S , Li C , Liu Q , Sun S , Yang M , Guo N , Wang X , Wang S , Liu Y , Wang G , Huang H , Shen Z
Ref : Sci Rep , 7 :4351 , 2017
Abstract : Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining beta-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets. A single administration of HBK001 in ICR mice can increase plasma incretins levels much more efficiently than linagliptin, a classic DPP4 inhibitor. Long-term treatment of HBK001 in KKAy mice can ameliorate hyperglycemia as well as improve glucose tolerance, while linagliptin fails to achieve such glucose-lowing effects despite inhibiting 95% of serum DPP4 activity. Moreover, HBK001 can increase first-phase insulin secretion in KKAy mice, suggesting a direct effect on islet beta-cells via GPR119 activation. Furthermore, HBK001 can improve islet morphology, increase beta-cell proliferation and up-regulate genes involved in improved beta-cell function. Thus, we have identified, designed and synthesized a novel dual-target compound, HBK001, which represents a promising therapeutic candidate for type 2 diabetes, especially for patients who are insensitive to current DPP4 inhibitors.
ESTHER : Huan_2017_Sci.Rep_7_4351
PubMedSearch : Huan_2017_Sci.Rep_7_4351
PubMedID: 28659588

Title : Cardiolipin remodeling: a regulatory hub for modulating cardiolipin metabolism and function - Ye_2016_J.Bioenerg.Biomembr_48_113
Author(s) : Ye C , Shen Z , Greenberg ML
Ref : J Bioenerg Biomembr , 48 :113 , 2016
Abstract : Cardiolipin (CL), the signature phospholipid of mitochondria, is involved in a plethora of cellular processes and is crucial for mitochondrial function and architecture. The de novo synthesis of CL in the mitochondria is followed by a unique remodeling process, in which CL undergoes cycles of deacylation and reacylation. Specific fatty acyl composition is acquired during this process, and remodeled CL contains predominantly unsaturated fatty acids. The importance of CL remodeling is underscored by the life-threatening genetic disorder Barth syndrome (BTHS), caused by mutations in tafazzin, which reacylates monolysocardiolipin (MLCL) generated from the deacylation of CL. Just as CL-deficient yeast mutants have been instrumental in elucidating functions of this lipid, the recently characterized CL-phospholipase mutant cld1delta and the tafazzin mutant taz1delta are powerful tools to understand the functions of CL remodeling. In this review, we discuss recent advances in understanding the role of CL in mitochondria with specific focus on the enigmatic functions of CL remodeling.
ESTHER : Ye_2016_J.Bioenerg.Biomembr_48_113
PubMedSearch : Ye_2016_J.Bioenerg.Biomembr_48_113
PubMedID: 25432572

Title : Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect - Xu_2014_BMC.Cancer_14_668
Author(s) : Xu H , Shen Z , Xiao J , Yang Y , Huang W , Zhou Z , Shen J , Zhu Y , Liu XY , Chu L
Ref : BMC Cancer , 14 :668 , 2014
Abstract : BACKGROUND: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
METHODS: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 x 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay.
RESULTS: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells. CONCLUSION: ZD55-AChE represented potential therapeutic effect for human gastric cancer.
ESTHER : Xu_2014_BMC.Cancer_14_668
PubMedSearch : Xu_2014_BMC.Cancer_14_668
PubMedID: 25220382

Title : Draft genome sequences of six enterohepatic helicobacter species isolated from humans and one from rhesus macaques - Shen_2014_Genome.Announc_2_e00857
Author(s) : Shen Z , Sheh A , Young SK , Abouelliel A , Ward DV , Earl AM , Fox JG
Ref : Genome Announc , 2 : , 2014
Abstract : Draft genome sequences of seven enterohepatic Helicobacter species, H. bilis, H. canadensis, H. canis, H. cinaedi, H. winghamensis, H. pullorum, and H. macacae, are presented. These isolates were obtained from clinical patients and a nonhuman primate. Due to potential zoonotic risks, we characterized antibiotic resistance markers and Helicobacter virulence factors.
ESTHER : Shen_2014_Genome.Announc_2_e00857
PubMedSearch : Shen_2014_Genome.Announc_2_e00857
PubMedID: 25212613
Gene_locus related to this paper: 9heli-c3xeg0

Title : Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins - Liu_2014_Acta.Pharm.Sin.B_4_135
Author(s) : Liu J , Huan Y , Li C , Liu M , Shen Z
Ref : Acta Pharm Sin B , 4 :135 , 2014
Abstract : Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2 mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors.
ESTHER : Liu_2014_Acta.Pharm.Sin.B_4_135
PubMedSearch : Liu_2014_Acta.Pharm.Sin.B_4_135
PubMedID: 26579375

Title : Discovery and optimization of orally active cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors - Debenham_2013_Bioorg.Med.Chem.Lett_23_6228
Author(s) : Debenham JS , Graham TH , Verras A , Zhang Y , Clements MJ , Kuethe JT , Madsen-Duggan C , Liu W , Bhatt UR , Chen D , Chen Q , Garcia-Calvo M , Geissler WM , He H , Li X , Lisnock J , Shen Z , Tong X , Tung EC , Wiltsie J , Xu S , Hale JJ , Pinto S , Shen DM
Ref : Bioorganic & Medicinal Chemistry Lett , 23 :6228 , 2013
Abstract : The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20 h post oral dose.
ESTHER : Debenham_2013_Bioorg.Med.Chem.Lett_23_6228
PubMedSearch : Debenham_2013_Bioorg.Med.Chem.Lett_23_6228
PubMedID: 24157366

Title : The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors - Graham_2012_Bioorg.Med.Chem.Lett_22_658
Author(s) : Graham TH , Shen HC , Liu W , Xiong Y , Verras A , Bleasby K , Bhatt UR , Chabin RM , Chen D , Chen Q , Garcia-Calvo M , Geissler WM , He H , Lassman ME , Shen Z , Tong X , Tung EC , Xie D , Xu S , Colletti SL , Tata JR , Hale JJ , Pinto S , Shen DM
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :658 , 2012
Abstract : Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC(50) values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied.
ESTHER : Graham_2012_Bioorg.Med.Chem.Lett_22_658
PubMedSearch : Graham_2012_Bioorg.Med.Chem.Lett_22_658
PubMedID: 22079761
Gene_locus related to this paper: human-PRCP

Title : Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors - Shen_2011_Bioorg.Med.Chem.Lett_21_1299
Author(s) : Shen HC , Ding FX , Zhou C , Xiong Y , Verras A , Chabin RM , Xu S , Tong X , Xie D , Lassman ME , Bhatt UR , Garcia-Calvo MM , Geissler W , Shen Z , Chen D , SinhaRoy R , Hale JJ , Tata JR , Pinto S , Shen DM , Colletti SL
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :1299 , 2011
Abstract : A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC(50)'s were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
ESTHER : Shen_2011_Bioorg.Med.Chem.Lett_21_1299
PubMedSearch : Shen_2011_Bioorg.Med.Chem.Lett_21_1299
PubMedID: 21315588
Gene_locus related to this paper: human-PRCP

Title : Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity - Zhou_2010_J.Med.Chem_53_7251
Author(s) : Zhou C , Garcia-Calvo M , Pinto S , Lombardo M , Feng Z , Bender K , Pryor KD , Bhatt UR , Chabin RM , Geissler WM , Shen Z , Tong X , Zhang Z , Wong KK , Roy RS , Chapman KT , Yang L , Xiong Y
Ref : Journal of Medicinal Chemistry , 53 :7251 , 2010
Abstract : Prolylcarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 microM) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP(-/-) and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a 1% reduction in PrCP KO mice.
ESTHER : Zhou_2010_J.Med.Chem_53_7251
PubMedSearch : Zhou_2010_J.Med.Chem_53_7251
PubMedID: 20857914
Gene_locus related to this paper: human-PRCP

Title : A novel molecular marker for early detection and evaluating prognosis of gastric cancer: N-myc downstream regulated gene-1 (NDRG1) - Jiang_2010_Scand.J.Gastroenterol_45_898
Author(s) : Jiang K , Shen Z , Ye Y , Yang X , Wang S
Ref : Scand J Gastroenterol , 45 :898 , 2010
Abstract : OBJECTIVE N-myc downstream regulated gene-1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 was recently found to significantly down regulate in a variety of different neoplasms. Its significance in gastric cancer has not been studied. MATERIALS AND METHODS: NDRG1 was detected at its protein level by immunohistochemistry in formalin-fixed and paraffin-embedded sections with a total of 110 pair gastric cancer specimens including tumor and corresponding paraneoplastic tissues; NDRG1 mRNA was detected by real time-polymerase chain reaction. Meanwhile, the correlations between NDRG1 and clinicopathological factors were observed. Overexpression of NDRG1 has influence on the biological behavior of gastric cancer cell, which was detected by cell growth assay, apoptosis assay, and in vitro motility and invasion assay. RESULTS: NDRG1 protein was down regulated in gastric cancer tissues, and the NDRG1 low expression rate was 73.6% (79/110). Moreover, NDRG1 expression has a significant inverse correlation with tumor stromal invasion, lymph node metastasis, pathological stage, but not with distant metastasis. The patients with low NDRG1 expression had a significantly shorter survival opportunity than those with high NDRG1 expression. In addition, overexpression of NDRG1 induced early apoptosis and inhibited SGC7901 cell proliferation and its motility and invasion capability.
CONCLUSIONS: NDRG1 plays a significant role in carcinogenesis and preventing the metastasis and invasion of gastric cancer cells. NDRG1 could be developed as a marker contributing to diagnosis and evaluating prognosis in gastric cancer, as well as a potential therapeutic target of gastric cancer.
ESTHER : Jiang_2010_Scand.J.Gastroenterol_45_898
PubMedSearch : Jiang_2010_Scand.J.Gastroenterol_45_898
PubMedID: 20388062

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 : A mass spectrometry plate reader: monitoring enzyme activity and inhibition with a Desorption\/Ionization on Silicon (DIOS) platform - Shen_2004_Chembiochem_5_921
Author(s) : Shen Z , Go EP , Gamez A , Apon JV , Fokin V , Greig M , Ventura M , Crowell JE , Blixt O , Paulson JC , Stevens RC , Finn MG , Siuzdak G
Ref : Chembiochem , 5 :921 , 2004
Abstract : A surface-based laser desorption/ionization mass spectrometry assay that makes use of Desorption/Ionization on Silicon Mass Spectrometry (DIOS-MS) has been developed to monitor enzyme activity and enzyme inhibition. DIOS-MS has been used to characterize inhibitors from a library and then to monitor their activity against selected enzyme targets, including proteases, glycotransferase, and acetylcholinesterase. An automated DIOS-MS system was also used as a high-throughput screen for the activity of novel enzymes and enzyme inhibitors. On two different commercially available instruments, a sampling rate of up to 38 inhibitors per minute was accomplished, with thousands of inhibitors being monitored. The ease of applying mass spectrometry toward developing enzyme assays and the speed of surface-based assays such as DIOS for monitoring inhibitor effectiveness and enzyme activity makes it attractive for a broad range of screening applications.
ESTHER : Shen_2004_Chembiochem_5_921
PubMedSearch : Shen_2004_Chembiochem_5_921
PubMedID: 15239048

Title : The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus - Suerbaum_2003_Proc.Natl.Acad.Sci.U.S.A_100_7901
Author(s) : Suerbaum S , Josenhans C , Sterzenbach T , Drescher B , Brandt P , Bell M , Droge M , Fartmann B , Fischer HP , Ge Z , Horster A , Holland R , Klein K , Konig J , Macko L , Mendz GL , Nyakatura G , Schauer DB , Shen Z , Weber J , Frosch M , Fox JG
Ref : Proc Natl Acad Sci U S A , 100 :7901 , 2003
Abstract : Helicobacter hepaticus causes chronic hepatitis and liver cancer in mice. It is the prototype enterohepatic Helicobacter species and a close relative of Helicobacter pylori, also a recognized carcinogen. Here we report the complete genome sequence of H. hepaticus ATCC51449. H. hepaticus has a circular chromosome of 1,799,146 base pairs, predicted to encode 1,875 proteins. A total of 938, 953, and 821 proteins have orthologs in H. pylori, Campylobacter jejuni, and both pathogens, respectively. H. hepaticus lacks orthologs of most known H. pylori virulence factors, including adhesins, the VacA cytotoxin, and almost all cag pathogenicity island proteins, but has orthologs of the C. jejuni adhesin PEB1 and the cytolethal distending toxin (CDT). The genome contains a 71-kb genomic island (HHGI1) and several genomic islets whose G+C content differs from the rest of the genome. HHGI1 encodes three basic components of a type IV secretion system and other virulence protein homologs, suggesting a role of HHGI1 in pathogenicity. The genomic variability of H. hepaticus was assessed by comparing the genomes of 12 H. hepaticus strains with the sequenced genome by microarray hybridization. Although five strains, including all those known to have caused liver disease, were indistinguishable from ATCC51449, other strains lacked between 85 and 229 genes, including large parts of HHGI1, demonstrating extensive variation of genome content within the species.
ESTHER : Suerbaum_2003_Proc.Natl.Acad.Sci.U.S.A_100_7901
PubMedSearch : Suerbaum_2003_Proc.Natl.Acad.Sci.U.S.A_100_7901
PubMedID: 12810954
Gene_locus related to this paper: helhp-q7vg13 , helhp-q7vgw2 , helhp-q7vig4 , helhp-q7vj57