The enzyme, dipeptidyl peptidase IV（DPP IV）, is a novel target for the treatment of type 2 diabetes. Dipeptidyl peptidase IV inhibition improves the impaired insulin secretion and decrease postprandial concentration...The enzyme, dipeptidyl peptidase IV（DPP IV）, is a novel target for the treatment of type 2 diabetes. Dipeptidyl peptidase IV inhibition improves the impaired insulin secretion and decrease postprandial concentrations of glucagon by enhancing the incretin hormone levels lucagon-like peptide-1（GLP-1） and glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide（GIP）. Recently, DPP IV inhibitors have attracted more and more attention, several of which have entered pre-clinical and clinical trials, and one has received approval for use as an anti-diabetic agent. Among the DPP IV inhibitors, two leading agents（sitagliptin and vildagliptin） have been shown to be effective in reducing glycosylated hemoglobin（HbAlc） and fasting plasma glucose（FPG） in patients with type 2 diabetes. This review summarizes the evidence supporting DPP IV inhibitors as potential antidiabetic agents.展开更多
The last few years important changes have occurred in the field of diabetes treatment.The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors,w...The last few years important changes have occurred in the field of diabetes treatment.The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors,while individualization of glycemic target is suggested.Furthermore,regulatory authorities now require evidence of cardiovascular(CV)safety in order to approve new antidiabetic agents.The most novel drug classes,i.e.,sodium-glucose transporter 2 inhibitors(SGLT2-i)and some glucagon-like peptide-1 receptor agonists(GLP-1 RA),have been demonstrated to reduce major adverse CV events and,thus,have a prominent position in the therapeutic algorithm of hyperglycemia.In this context,the role of previously used hypoglycemic agents,including dipeptidyl peptidase 4(DPP-4)inhibitors,has been modified.DPP-4 inhibitors have a favorable safety profile,do not cause hypoglycemia or weight gain and do not require dose uptitration.Furthermore,they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes.Still,though,they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA.Overall,DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.展开更多
The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bio...The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.展开更多
Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research.Here,we took a retrospective validation approach built on the mutuality between s...Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research.Here,we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by a-naphthyl isothiocyanate(ANIT).We found that carboxylesterase 1(CES1),as an intrahepatic marker,and dipeptidyl peptidase 4(DPP-IV),as an extrahepatic marker,can reflect the different pathophysiologies of liver injury.Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state,respectively.While the levels of the conventional serological biomarkers alkaline phosphatase(ALP),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were all concomitantly elevated in serum and tissues after ANIT-induced injury,the levels of bile acids decreased in bile,increased in serum,and ascended in intrahepatic tissue.Although the level of γ-glutamyl transpeptidase(γ-GT)changed in an opposite direction,the duration was much shorter than that of CES1 and was quickly restored to normal levels.Therefore,among the abovementioned biomarkers,only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation.CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid(UDCA;single component)and Qing Fei Pai Du Decoction(QFPDD;multicomponent).We found that both QFPDD and UDCA attenuated ANIT-induced liver damage.UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and antiinflammatory effects than QFPDD,whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage.Our data highlights the potential of the combined use of CES1(as an intrahepatic marker of liver damage)and DPP-IV(as an extrahepatic marker of inflammation)for the accurate evaluation and tracking of liver-specific injury—an application that allows for the differentiation of liver damage and inflammatory liver injury.展开更多
AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were s...AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.展开更多
Emotional and motivational disorders in adults are often considered to be the result of altered neurodevelopment. Clinical and experimental data provide evidence that serine protease dipeptidyl peptidase-IV (DPP-IV, E...Emotional and motivational disorders in adults are often considered to be the result of altered neurodevelopment. Clinical and experimental data provide evidence that serine protease dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) is involved in the pathophysiology of psycho-emotional disorders. Recently, we have shown that adolescent and adult rats exhibit an increase in anxiety and depression-related behaviors after neonatal administration of a synthetic non-competitive inhibitor of DPP-IV, methionyl-2(S)-cyano-pyrrolidine. In the present study, we tested the effects of two competitive, selective DPP-IV inhibitors, sitagliptin (4 mg/kg) and diprotin A (2 mg/kg), administered at postnatal days 5 - 18 on the emotional and motivational behavior of adolescent and adult rats. We observed increased anxiety in one-month-old diprotin A- or sitagliptin-treated rats in the elevated plus maze;diprotin A also enhanced the animals’ anxiety score using a ranked scale for evaluating anxiety and phobias. In the sucrose consumption and preference test, depressive-like behavior was pronounced in both the diprotin A- and sitagliptin-treated one-month-old animals, while only the diprotin A-treated rats exhibited a decrease in sucrose consumption at the age of 2 months. The diprotin A-treated rats also demonstrated behavioral despair and decreased activity in the forced swimming test within 1 - 3 months of age. Increased aggression was observed in 1 - 3-month-old diprotin A-treated rats and in two-month-old sitagliptin-treated rats. These findings support the hypothesis that DPP-IV is involved in the genesis of emotional and motivational disorders. Additionally, the results show that diprotin А impairs the adolescent and adult rats’ behavior more significantly than sitagliptin when the animals were treated with the DPP-IV inhibitors in the early postnatal period.展开更多
Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of hu...Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction （RT-PCR） and Southern-blot analysis. Results： A new transcript variant of the human dipeptidyl peptidase （DPP8）, exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 （DPP8-v3）. The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. Conclusion： DPPS-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility. （Asian J Androl 2005 Sep; 7： 245-255）展开更多
Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatme...Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.展开更多
AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for nonparenchymal cell (NPC) transplantation.METHODS: Livers of dipeptidyl peptidase(DPP)-deficient rats were pre-c...AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for nonparenchymal cell (NPC) transplantation.METHODS: Livers of dipeptidyl peptidase(DPP)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lob-ule. DPP-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation.RESULTS: Host liver staining demonstrated 3 different repopulation types. Well def ined clusters of donor-derived hepatocytes with canalicular expression of DPP were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPP-positive duct-like structures which co-localized with biliary epithelial CD49f.CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells.展开更多
Cystic fibrosis(CF)is a common autosomal recessive disease.Life expectancy of patients with CF continues to improve mainly driven by the evolving therapies for CF-related organ dysfunction.The prevalence of CF-related...Cystic fibrosis(CF)is a common autosomal recessive disease.Life expectancy of patients with CF continues to improve mainly driven by the evolving therapies for CF-related organ dysfunction.The prevalence of CF-related diabetes(CFRD)increases exponentially as patients’age.Clinical care guidelines for CFRD from 2010,recommend insulin as the mainstay of treatment.Many patients with CFRD may not require exogenous insulin due to the heterogeneity of this clinical entity.Maintenance of euglycemia by enhancing endogenous insulin production,secretion and degradation with novel pharmacological therapies like glucagonlike peptide-1 agonist is an option that remains to be fully explored.As such,the scope of this article will focus on our perspective of glucagon-like peptide-1 receptor agonist in the context of CFRD.Other potential options such as sodiumglucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors and their impact on this patient population is limited and further studies are required.展开更多
Subject Code:H30With the support by the National Natural Science Foundation of China and National Basic Research Program of China,the group led by Prof.Ge Guangbo(葛广波)and Prof.Yang Ling(杨凌)from the Laboratory of ...Subject Code:H30With the support by the National Natural Science Foundation of China and National Basic Research Program of China,the group led by Prof.Ge Guangbo(葛广波)and Prof.Yang Ling(杨凌)from the Laboratory of Pharmaceutical Resource Discovery,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,reported a highly specific ratiometric two-photon fluorescent probe to detect展开更多
Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized i...Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine.Among the designed compounds,41d-1 was the most po tent one with an IC_(50) value of 16.00 nM.展开更多
OBJECTIVE: To investigate the protective effects and molecular mechanisms of Lizhong decoction( 理中汤, LZD) against non-alcoholic fatty liver disease(NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for fou...OBJECTIVE: To investigate the protective effects and molecular mechanisms of Lizhong decoction( 理中汤, LZD) against non-alcoholic fatty liver disease(NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined. RESULTS: Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage,inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor(PPAR)-γ expression, and suppressed dipeptidyl peptidase 4(DPP4) expression in the liver. CONCLUSION: It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.展开更多
Thirteen thiomorpholine-bearing compounds were designed and synthesized as dipeptidyl peptidase IV（DPP-IV） inhibitors, with natural and non-natural L-amino acids as the starting materials.Their structures were chara...Thirteen thiomorpholine-bearing compounds were designed and synthesized as dipeptidyl peptidase IV（DPP-IV） inhibitors, with natural and non-natural L-amino acids as the starting materials.Their structures were characterized by ~1H NMR,^（13）C NMR and HR-MS.The target compounds were screened for the DPP-IV inhibition,and the preliminary SAR result was obtained.Particularly, compounds 4c,4d and 4f with good DPP-IV inhibition in vitro were further evaluated through a mouse oral glucose tolerance test （OGTT）.The preliminary result showed the potential value for further studies on those thiomorpholine-bearing compounds as DPP-IV inhibitors.展开更多
文摘The enzyme, dipeptidyl peptidase IV（DPP IV）, is a novel target for the treatment of type 2 diabetes. Dipeptidyl peptidase IV inhibition improves the impaired insulin secretion and decrease postprandial concentrations of glucagon by enhancing the incretin hormone levels lucagon-like peptide-1（GLP-1） and glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide（GIP）. Recently, DPP IV inhibitors have attracted more and more attention, several of which have entered pre-clinical and clinical trials, and one has received approval for use as an anti-diabetic agent. Among the DPP IV inhibitors, two leading agents（sitagliptin and vildagliptin） have been shown to be effective in reducing glycosylated hemoglobin（HbAlc） and fasting plasma glucose（FPG） in patients with type 2 diabetes. This review summarizes the evidence supporting DPP IV inhibitors as potential antidiabetic agents.
文摘The last few years important changes have occurred in the field of diabetes treatment.The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors,while individualization of glycemic target is suggested.Furthermore,regulatory authorities now require evidence of cardiovascular(CV)safety in order to approve new antidiabetic agents.The most novel drug classes,i.e.,sodium-glucose transporter 2 inhibitors(SGLT2-i)and some glucagon-like peptide-1 receptor agonists(GLP-1 RA),have been demonstrated to reduce major adverse CV events and,thus,have a prominent position in the therapeutic algorithm of hyperglycemia.In this context,the role of previously used hypoglycemic agents,including dipeptidyl peptidase 4(DPP-4)inhibitors,has been modified.DPP-4 inhibitors have a favorable safety profile,do not cause hypoglycemia or weight gain and do not require dose uptitration.Furthermore,they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes.Still,though,they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA.Overall,DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.
文摘The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.
基金This article is supported by the National Key Research and Development Program of China(2017YFC1702000,2020YFC0845400,and 2021YFE0200900)National Natural Science Foundation of China(81773810,81922070,and 81973393).The authors would like to thank Peter for his help in publishing the article,and the support provided by Zhaoyan(Suzhou)New Drug Research Center Co,.Ltd.
文摘Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research.Here,we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by a-naphthyl isothiocyanate(ANIT).We found that carboxylesterase 1(CES1),as an intrahepatic marker,and dipeptidyl peptidase 4(DPP-IV),as an extrahepatic marker,can reflect the different pathophysiologies of liver injury.Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state,respectively.While the levels of the conventional serological biomarkers alkaline phosphatase(ALP),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were all concomitantly elevated in serum and tissues after ANIT-induced injury,the levels of bile acids decreased in bile,increased in serum,and ascended in intrahepatic tissue.Although the level of γ-glutamyl transpeptidase(γ-GT)changed in an opposite direction,the duration was much shorter than that of CES1 and was quickly restored to normal levels.Therefore,among the abovementioned biomarkers,only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation.CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid(UDCA;single component)and Qing Fei Pai Du Decoction(QFPDD;multicomponent).We found that both QFPDD and UDCA attenuated ANIT-induced liver damage.UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and antiinflammatory effects than QFPDD,whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage.Our data highlights the potential of the combined use of CES1(as an intrahepatic marker of liver damage)and DPP-IV(as an extrahepatic marker of inflammation)for the accurate evaluation and tracking of liver-specific injury—an application that allows for the differentiation of liver damage and inflammatory liver injury.
文摘AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.
文摘Emotional and motivational disorders in adults are often considered to be the result of altered neurodevelopment. Clinical and experimental data provide evidence that serine protease dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) is involved in the pathophysiology of psycho-emotional disorders. Recently, we have shown that adolescent and adult rats exhibit an increase in anxiety and depression-related behaviors after neonatal administration of a synthetic non-competitive inhibitor of DPP-IV, methionyl-2(S)-cyano-pyrrolidine. In the present study, we tested the effects of two competitive, selective DPP-IV inhibitors, sitagliptin (4 mg/kg) and diprotin A (2 mg/kg), administered at postnatal days 5 - 18 on the emotional and motivational behavior of adolescent and adult rats. We observed increased anxiety in one-month-old diprotin A- or sitagliptin-treated rats in the elevated plus maze;diprotin A also enhanced the animals’ anxiety score using a ranked scale for evaluating anxiety and phobias. In the sucrose consumption and preference test, depressive-like behavior was pronounced in both the diprotin A- and sitagliptin-treated one-month-old animals, while only the diprotin A-treated rats exhibited a decrease in sucrose consumption at the age of 2 months. The diprotin A-treated rats also demonstrated behavioral despair and decreased activity in the forced swimming test within 1 - 3 months of age. Increased aggression was observed in 1 - 3-month-old diprotin A-treated rats and in two-month-old sitagliptin-treated rats. These findings support the hypothesis that DPP-IV is involved in the genesis of emotional and motivational disorders. Additionally, the results show that diprotin А impairs the adolescent and adult rats’ behavior more significantly than sitagliptin when the animals were treated with the DPP-IV inhibitors in the early postnatal period.
文摘Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction （RT-PCR） and Southern-blot analysis. Results： A new transcript variant of the human dipeptidyl peptidase （DPP8）, exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 （DPP8-v3）. The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. Conclusion： DPPS-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility. （Asian J Androl 2005 Sep; 7： 245-255）
基金supported by the National Natural Science Foundation of China,Nos.81771271(to JF),31800898(to WL),81430025(to JYL),and U1801681(to JYL)Key Research and Development Program of Liaoning Province,No.2020JH2/10300047(to JF)+1 种基金the Key Field Research Development Program of Guangdong Province,No.2018B030337001(to JYL)the Outstanding Scientific Fund of Shengjing Hospital,No.M0475(to JF)。
文摘Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.
文摘AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for nonparenchymal cell (NPC) transplantation.METHODS: Livers of dipeptidyl peptidase(DPP)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lob-ule. DPP-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation.RESULTS: Host liver staining demonstrated 3 different repopulation types. Well def ined clusters of donor-derived hepatocytes with canalicular expression of DPP were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPP-positive duct-like structures which co-localized with biliary epithelial CD49f.CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells.
文摘Cystic fibrosis(CF)is a common autosomal recessive disease.Life expectancy of patients with CF continues to improve mainly driven by the evolving therapies for CF-related organ dysfunction.The prevalence of CF-related diabetes(CFRD)increases exponentially as patients’age.Clinical care guidelines for CFRD from 2010,recommend insulin as the mainstay of treatment.Many patients with CFRD may not require exogenous insulin due to the heterogeneity of this clinical entity.Maintenance of euglycemia by enhancing endogenous insulin production,secretion and degradation with novel pharmacological therapies like glucagonlike peptide-1 agonist is an option that remains to be fully explored.As such,the scope of this article will focus on our perspective of glucagon-like peptide-1 receptor agonist in the context of CFRD.Other potential options such as sodiumglucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors and their impact on this patient population is limited and further studies are required.
文摘Subject Code:H30With the support by the National Natural Science Foundation of China and National Basic Research Program of China,the group led by Prof.Ge Guangbo(葛广波)and Prof.Yang Ling(杨凌)from the Laboratory of Pharmaceutical Resource Discovery,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,reported a highly specific ratiometric two-photon fluorescent probe to detect
基金This work was supported by the National Key Research and Development Program(No.2016YFA0502304 to H.L.)the National Natural Science Foundation of China(No.81825020 to H.L,No.81803437 to SL.)+3 种基金the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(No.2018ZX09711002)the Fundamental Research Funds for the Central Universities,Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund(the second phase)under Grant No.U1501501Shiliang Li is sponsored by Shanghai Sailing Program(No.18YF1405100)Honglin Li is also sponsored by the National Program for Special Supports of Emi nent Professionals and the National Program for Support of Top-notch Young Professionals.
文摘Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine.Among the designed compounds,41d-1 was the most po tent one with an IC_(50) value of 16.00 nM.
基金Supported by Backbone Talents for TCM Clinical Characteristic Technology Inheritance Foundation of State Administration of Traditional Chinese Medicine:Protective Effects and Mechanisms of Lizhong Decoction Against Non-Alcoholic Fatty Liver Disease in a Rat Model [National Education Letter of Traditional Chinese Medicine (2018) No. 224]。
文摘OBJECTIVE: To investigate the protective effects and molecular mechanisms of Lizhong decoction( 理中汤, LZD) against non-alcoholic fatty liver disease(NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined. RESULTS: Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage,inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor(PPAR)-γ expression, and suppressed dipeptidyl peptidase 4(DPP4) expression in the liver. CONCLUSION: It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.
基金the Fundamental Scientific Research Fund ofInstitute of Materia Medica(Li Peng 504-Basic 10 DPP IV inhibitor)for financial support on this project
文摘Thirteen thiomorpholine-bearing compounds were designed and synthesized as dipeptidyl peptidase IV（DPP-IV） inhibitors, with natural and non-natural L-amino acids as the starting materials.Their structures were characterized by ~1H NMR,^（13）C NMR and HR-MS.The target compounds were screened for the DPP-IV inhibition,and the preliminary SAR result was obtained.Particularly, compounds 4c,4d and 4f with good DPP-IV inhibition in vitro were further evaluated through a mouse oral glucose tolerance test （OGTT）.The preliminary result showed the potential value for further studies on those thiomorpholine-bearing compounds as DPP-IV inhibitors.
