Objective To investigate the effects of the topical use of aprotinin on thebasis of comprehensive blood conservations in cardiopulmonary bypass (CPB). Methods In a prospectiveclinical trial, 20 patients were randomly ...Objective To investigate the effects of the topical use of aprotinin on thebasis of comprehensive blood conservations in cardiopulmonary bypass (CPB). Methods In a prospectiveclinical trial, 20 patients were randomly divided into 2 groups. Control group: placebo was usedtopically. Aprotinin group: aprotinin was poured into the pericardial cavity before closure of thesternotomy. Before and 24h after surgery, hemoglobin (Hb), hematocrit (Hct), bleeding time (BT),clotting time (CT) and prothrombin time (PT) were measured. Meanwhile, amounts of the mediastinaldrainage and the hemoglobin loss were observed at 0, 2, 6 and 24h after operation. The samples fromthe mediastinal drainage were also collected to measure D-Dimer (D-D), tissue type plasminogenactivator (t-PA) activity, plasminogen activator inhibitor (PAI) activity and protein C (PC).Results In Aprotinin group, D-D, t-PA activity and PC were significantly reduced, compared withthose in Control group (P<0.05, P<0.05, P<0.01). On the contrary, PAI activity was significantlyincreased, compared with that in Control group. Amounts of the mediastinal drainage and thehemoglobin loss were decreased by 43% and 52%, compared with those in Control group. Conclusion Ourresults suggest that the topical use of aprotinin can have better effects on the basis ofcomprehensive moderate blood conservation.展开更多
Three angiotensin I converting enzyme(ACE) inhibition peptides were isolated from sandworm Sipunculus nudus protein hydrolysate prepared using protamex. Consecutive purification methods, including size exclusion chrom...Three angiotensin I converting enzyme(ACE) inhibition peptides were isolated from sandworm Sipunculus nudus protein hydrolysate prepared using protamex. Consecutive purification methods, including size exclusion chromatography and reverse-phase high performance liquid chromatography(RP-HPLC), were used to isolate the ACE inhibition peptides. The amino acid sequences of the peptides were identified as Ile-Asn-Asp, Val-Glu-Pro-Gly and Leu-Ala-Asp-Glu-Phe. The IC_(50) values of the purified peptides for ACE inhibition activity were 34.72 μmol L^(-1), 20.55 μmol L^(-1) and 22.77 μmol L^(-1), respectively. These results suggested that S. nudus proteins contain specific peptides that can be released by enzymatic hydrolysis. This study may provide an experimental basis for further systematic research, rational development and clinical utilization of sandworm resources.展开更多
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitill valsartan (previously known as LCZ696) is a new oral agent approved for...Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitill valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-Ⅱ receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.展开更多
AIM: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our...AIM: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our purpose was to determine the correlation between the expression of cysteine peptidases and their endogenous inhibitors,and the level of vitamin E in sera of patients with colorectal cancer in comparison with healthy individuals.METHODS: The levels of cysteine peptidases and their inhibitors were determined in the sera of patients with primary and metastatic colorectal carcinoma and healthy individuals using fluorogenic substrate, and the level of vitamin E was determined by HPLC.RESULTS: The levels of cysteine peptidases and their inhibitors were significantly higher in the metastatic colorectal cancer patients than that in the healthy controls (P<0.05).The activity of CP increased 2.2-fold, CPI 2.8-fold and vitamin E decreased 3.4-fold in sera of patients with metastasis in comparison with controls. The level of vitamin E in healthy individuals was higher, whereas the activity of cysteine peptidases and their inhibitors associated with complexes was lower than that in patients with cancer of the digestive tract.CONCLUSION: These results suggest that the serum levels of CP and their inhibitors could be an indicator of the prognosis for patients with metastatic colorectal cancer. Vitamin E can be administered prophylactically to prevent digestive tract neoplasmas.展开更多
Objective: To investigate the role of aprotinin blood anesthesia used in hepatotomy. Methods: Patients with liver cancer undergoing hepatotomy were divided into two groups. In experimental group (40 patients) a loadin...Objective: To investigate the role of aprotinin blood anesthesia used in hepatotomy. Methods: Patients with liver cancer undergoing hepatotomy were divided into two groups. In experimental group (40 patients) a loading dose with 1112 EPU aprotinin and maintained by 278 EPU/h was used until 2 h after operation. The control group (42 patients) was treated with 0.9% normal saline. The venous blood was withdrew for blood routine, thrombelastography and coagulable test at the time of preinduced, 1 h, 2 h and 4 h following the operation beginning, 6 h and 12 h after operation. The change of TEG and coagulable profile were monitored during the whole surgery. The volume of blood transfusion and hemorrhage between two groups were compared. Results: After the usage of aprotinin, the preoperative hypercoagulability of the experimental group was remitted and the coagulative state was kept relatively stable during the operation. However, hypercoagulability of the control group aggravated following the operation beginning and some of them switched to hypocoagulability. The volumes and rates of hemorrhage and transfusion were smaller in the experimental group than in the control group. Conclusion: Aprotinin can stabilize the coagulable state, reduce the volumes and rates of hemorrhage and transfusion, and is worth using in the surgery of operations of liver cancer.展开更多
AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera afte...AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma. METHODS: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates. RESULTS: Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 μg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment(P<0.0001) CONCLUSION: The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.展开更多
AIM: To investigate the effect of selective Cyclooxygenase-2 (COX-2) inhibitor 4-[5-(4-Chloro-phenyl)-3- (trifluoromethyl)- 1H-pyrazol- 1-yl] benzenesulfonamide (SC-236), on the cholecystokinin (CCK)-octape...AIM: To investigate the effect of selective Cyclooxygenase-2 (COX-2) inhibitor 4-[5-(4-Chloro-phenyl)-3- (trifluoromethyl)- 1H-pyrazol- 1-yl] benzenesulfonamide (SC-236), on the cholecystokinin (CCK)-octapeptideinduced acute pancreatitis (AP) in rats. METHODS: Wistar rat weighing 240 g to 260 g were divided into three groups. (1) Normal DMSO treated group, (2) SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous (i.v.) catheter, followed by 75 μg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. (3) Dimethyl sulfoxide (DMSO) treated group: an identical protocol was used in this group as in the SC-236 cohort (see 2. above). Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats. RESULTS: SC-236 improved the severity of CCK- octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight (p.w/ b.w) ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein (HSP)-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-KB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP. CONCLUSION: Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.展开更多
As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse even...As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events (AE) and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus (T2DM). Randomized clinical trials (RCTs) comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference (WMD) was used to analyze the effect of hypoglycemic agents on HbAlc, weight and fasting plasma glucose (FPG). While the patients who achieved HbAlc〈7.0% and had AE were analyzed as relative risks (RR). A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbAlc compared with placebo was certified for 2.5 mg/day saxagliptin (WMD = -0.45%, 95% CI, -0.48% to -0.42%) and 5 mg/d saxagliptin (WMD = -0.52%, 95% CI, -0.60% to -0.44%). Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c〈7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia (RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40) and serious adverse experiences (RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13). No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections. The present study showed that saxagliptin was effective in improving glycaemic control in T2DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.展开更多
On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method...On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.展开更多
This study investigated the effect of heat treatment combined with acid and alkali on the angiotensin-I- converting enzyme (ACE) inhibitory activity of peptides derived from bovine casein. The free amino group conte...This study investigated the effect of heat treatment combined with acid and alkali on the angiotensin-I- converting enzyme (ACE) inhibitory activity of peptides derived from bovine casein. The free amino group content, color, and cytotoxicity of the peptides were measured under different conditions. When heated at 100 ℃ in the pH range from 9.0 to 12.0, ACE inhibitory activity was reduced and the appearance of the peptides was significantly darkened. After thermal treatment in the presence of acid and alkali, the free amino group content of ACE inhibitory peptides decreased markedly. High temperature and prolonged heating also resulted in the loss of ACE inhibitory activity, the loss of free amino groups, and the darker coloration of bovine casein-derived peptides. However, ACE inhibitory peptides, within a concentration range of from 0.01 to 0.2 mg/ml, showed no cytotoxicity to Caco-2 and ECV-304 cell lines after heat treatment. This indicated that high temperature and alkaline heat treatment impaired the stability of bovine casein-derived ACE inhibitory peptides.展开更多
To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro an...To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.展开更多
基金Supported by the Jiangsu Health Bureau Grand (B9606)
文摘Objective To investigate the effects of the topical use of aprotinin on thebasis of comprehensive blood conservations in cardiopulmonary bypass (CPB). Methods In a prospectiveclinical trial, 20 patients were randomly divided into 2 groups. Control group: placebo was usedtopically. Aprotinin group: aprotinin was poured into the pericardial cavity before closure of thesternotomy. Before and 24h after surgery, hemoglobin (Hb), hematocrit (Hct), bleeding time (BT),clotting time (CT) and prothrombin time (PT) were measured. Meanwhile, amounts of the mediastinaldrainage and the hemoglobin loss were observed at 0, 2, 6 and 24h after operation. The samples fromthe mediastinal drainage were also collected to measure D-Dimer (D-D), tissue type plasminogenactivator (t-PA) activity, plasminogen activator inhibitor (PAI) activity and protein C (PC).Results In Aprotinin group, D-D, t-PA activity and PC were significantly reduced, compared withthose in Control group (P<0.05, P<0.05, P<0.01). On the contrary, PAI activity was significantlyincreased, compared with that in Control group. Amounts of the mediastinal drainage and thehemoglobin loss were decreased by 43% and 52%, compared with those in Control group. Conclusion Ourresults suggest that the topical use of aprotinin can have better effects on the basis ofcomprehensive moderate blood conservation.
基金supported by research grant of Guangxi Key Laboratory Traditional Chinese Medicine Quality Standards (No. GXGZZK201501)the Open Research Fund Program of Guangxi Key Laboratory of Marine Biotechnology (No. GLMBT-201407)+1 种基金partly supported by Shanghai Fengxian District Science and Technology Project (Nos. 20141001 and 20151205)Shanghai No. 6 People’s Medical Group Project and research project of Shanghai municipal health and Family Planning Commission (No. 201540027)
文摘Three angiotensin I converting enzyme(ACE) inhibition peptides were isolated from sandworm Sipunculus nudus protein hydrolysate prepared using protamex. Consecutive purification methods, including size exclusion chromatography and reverse-phase high performance liquid chromatography(RP-HPLC), were used to isolate the ACE inhibition peptides. The amino acid sequences of the peptides were identified as Ile-Asn-Asp, Val-Glu-Pro-Gly and Leu-Ala-Asp-Glu-Phe. The IC_(50) values of the purified peptides for ACE inhibition activity were 34.72 μmol L^(-1), 20.55 μmol L^(-1) and 22.77 μmol L^(-1), respectively. These results suggested that S. nudus proteins contain specific peptides that can be released by enzymatic hydrolysis. This study may provide an experimental basis for further systematic research, rational development and clinical utilization of sandworm resources.
文摘Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitill valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-Ⅱ receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.
文摘AIM: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our purpose was to determine the correlation between the expression of cysteine peptidases and their endogenous inhibitors,and the level of vitamin E in sera of patients with colorectal cancer in comparison with healthy individuals.METHODS: The levels of cysteine peptidases and their inhibitors were determined in the sera of patients with primary and metastatic colorectal carcinoma and healthy individuals using fluorogenic substrate, and the level of vitamin E was determined by HPLC.RESULTS: The levels of cysteine peptidases and their inhibitors were significantly higher in the metastatic colorectal cancer patients than that in the healthy controls (P<0.05).The activity of CP increased 2.2-fold, CPI 2.8-fold and vitamin E decreased 3.4-fold in sera of patients with metastasis in comparison with controls. The level of vitamin E in healthy individuals was higher, whereas the activity of cysteine peptidases and their inhibitors associated with complexes was lower than that in patients with cancer of the digestive tract.CONCLUSION: These results suggest that the serum levels of CP and their inhibitors could be an indicator of the prognosis for patients with metastatic colorectal cancer. Vitamin E can be administered prophylactically to prevent digestive tract neoplasmas.
文摘Objective: To investigate the role of aprotinin blood anesthesia used in hepatotomy. Methods: Patients with liver cancer undergoing hepatotomy were divided into two groups. In experimental group (40 patients) a loading dose with 1112 EPU aprotinin and maintained by 278 EPU/h was used until 2 h after operation. The control group (42 patients) was treated with 0.9% normal saline. The venous blood was withdrew for blood routine, thrombelastography and coagulable test at the time of preinduced, 1 h, 2 h and 4 h following the operation beginning, 6 h and 12 h after operation. The change of TEG and coagulable profile were monitored during the whole surgery. The volume of blood transfusion and hemorrhage between two groups were compared. Results: After the usage of aprotinin, the preoperative hypercoagulability of the experimental group was remitted and the coagulative state was kept relatively stable during the operation. However, hypercoagulability of the control group aggravated following the operation beginning and some of them switched to hypocoagulability. The volumes and rates of hemorrhage and transfusion were smaller in the experimental group than in the control group. Conclusion: Aprotinin can stabilize the coagulable state, reduce the volumes and rates of hemorrhage and transfusion, and is worth using in the surgery of operations of liver cancer.
文摘AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma. METHODS: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates. RESULTS: Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 μg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment(P<0.0001) CONCLUSION: The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.
基金Supported by the Ministry of Science & Technology/Korea Science & Engineering Foundation through the Vestibuloco-chlear Research Center at Wonkwang University, No. R13-2002- 055-00000-0
文摘AIM: To investigate the effect of selective Cyclooxygenase-2 (COX-2) inhibitor 4-[5-(4-Chloro-phenyl)-3- (trifluoromethyl)- 1H-pyrazol- 1-yl] benzenesulfonamide (SC-236), on the cholecystokinin (CCK)-octapeptideinduced acute pancreatitis (AP) in rats. METHODS: Wistar rat weighing 240 g to 260 g were divided into three groups. (1) Normal DMSO treated group, (2) SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous (i.v.) catheter, followed by 75 μg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. (3) Dimethyl sulfoxide (DMSO) treated group: an identical protocol was used in this group as in the SC-236 cohort (see 2. above). Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats. RESULTS: SC-236 improved the severity of CCK- octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight (p.w/ b.w) ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein (HSP)-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-KB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP. CONCLUSION: Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.
基金Xinjiang Medical University Scientific Research and Innovation Foundation(Grant No.XYDCX2014117)
文摘As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events (AE) and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus (T2DM). Randomized clinical trials (RCTs) comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference (WMD) was used to analyze the effect of hypoglycemic agents on HbAlc, weight and fasting plasma glucose (FPG). While the patients who achieved HbAlc〈7.0% and had AE were analyzed as relative risks (RR). A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbAlc compared with placebo was certified for 2.5 mg/day saxagliptin (WMD = -0.45%, 95% CI, -0.48% to -0.42%) and 5 mg/d saxagliptin (WMD = -0.52%, 95% CI, -0.60% to -0.44%). Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c〈7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia (RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40) and serious adverse experiences (RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13). No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections. The present study showed that saxagliptin was effective in improving glycaemic control in T2DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.
基金Natural Science Foundation of China for the financial support(Grant No.30772626)
文摘On the basis of the Michael-addition mechanism of classical proteasome inhibitors, six dipeptide vinyl sulfonamide and dipeptide vinyl sulfonate derivatives were designed and synthesized. Moreover, an efficient method for the synthesis of g-amino vinyl sulfonamides, key intermediates to the target molecules, was developed via the Wittig-Horner reaction of peptide aldehyde with Wittig reagents derived from methanesulfonamides.
基金supported by the Innovative Research Team of Higher Education of Heilongjiang Province(No.2010td11)the National Natural Science Foundation of China(No.31000801)+1 种基金the National Key Technology R&D Program of China during the 12th Five-Year Plan Period(No.2013BAD18B06)the 2009 Doctoral Science Research of Northeast Agricultural University,China
文摘This study investigated the effect of heat treatment combined with acid and alkali on the angiotensin-I- converting enzyme (ACE) inhibitory activity of peptides derived from bovine casein. The free amino group content, color, and cytotoxicity of the peptides were measured under different conditions. When heated at 100 ℃ in the pH range from 9.0 to 12.0, ACE inhibitory activity was reduced and the appearance of the peptides was significantly darkened. After thermal treatment in the presence of acid and alkali, the free amino group content of ACE inhibitory peptides decreased markedly. High temperature and prolonged heating also resulted in the loss of ACE inhibitory activity, the loss of free amino groups, and the darker coloration of bovine casein-derived peptides. However, ACE inhibitory peptides, within a concentration range of from 0.01 to 0.2 mg/ml, showed no cytotoxicity to Caco-2 and ECV-304 cell lines after heat treatment. This indicated that high temperature and alkaline heat treatment impaired the stability of bovine casein-derived ACE inhibitory peptides.
基金National Natural Science Foundation of China (Grant No.30772626)
文摘To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.