BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,severa...BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.展开更多
AIM:To examine whether a dose-up to 900 mg of ursodeoxycholic acid(UDCA) decreases transaminases in hepatitis C patients.METHODS:From January to December 2007,patients with chronic hepatitis C or compensated liver cir...AIM:To examine whether a dose-up to 900 mg of ursodeoxycholic acid(UDCA) decreases transaminases in hepatitis C patients.METHODS:From January to December 2007,patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus(HCV)(43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study.Blood parameters were examined at 4,8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d.RESULTS:Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT) levels were signifi cantly decreased following the administration of 900 mg/d as compared to 600 mg/d.The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L,while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L.Platelet count tended to increase after the dose-up of UDCA,although it did not show a statistically signifi cant level(P=0.05).Minor adverse events were observed in 3 cases,although no drop-outs from the study occurred.CONCLUSION:Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT,AST,and GGT levels in patients with HCV-related chronic liver disease.展开更多
Irritable bowel syndrome(IBS)is an important health care concern.Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS.Some dietary intake could contribute to produce various ...Irritable bowel syndrome(IBS)is an important health care concern.Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS.Some dietary intake could contribute to produce various metabolites including Damino acids by the fermentation by the gut microbiota.D-amino acids are the enantiomeric counterparts of L-amino acids,in general,which could play key roles in cellular physiological processes against various oxidative stresses.Therefore,the presence of D-amino acids has been shown to be linked to the protection of several organs in the body.In particular,the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids.Here,we would like to shed light on the roles of D-amino acids,which could be used for the treatment of IBS.展开更多
Immobilization of D-amino acid dehydrogenase(DAADH)by the assembly of peptide linker was studied for the biosynthesis of Dphenylalanine.Hybrid material of zeolitic imidazolate framework-8(ZIF-8)combined with reduced g...Immobilization of D-amino acid dehydrogenase(DAADH)by the assembly of peptide linker was studied for the biosynthesis of Dphenylalanine.Hybrid material of zeolitic imidazolate framework-8(ZIF-8)combined with reduced graphene oxide(RGO)was applied for the immobilization of DAADH from Ureibacillus thermosphaericus.The recovery rate of DAADH/ZIF-8/RGO was 165.6%.DAADH/ZIF-8/RGO remained 53.4%of its initial activity at 50°C for 10 h while the free enzyme was inactivated.DAADH/ZIF-8/RGO maintained 70.5%activity in hyperalkaline solution with pH 12.Kinetic parameters indicated that DAADH/ZIF-8/RGO had greater affinity of phenylpyruvate as V_(max)/K_(m)of DAADH/ZIF-8/RGO was 1.27-fold than free enzyme.After seven recycles,the activity of DAADH/ZIF-8/RGO remained 64.3%.Furthermore,one-step separation and in situ immobilization of DAADH by ZIF-8/RGO/Ni was carried out with 1.5-fold activity enhancement.Combining peptide linker and metal-organic framework(MOF)immobilization,thermostability and activity of the immobilized DAADH were significantly improved.展开更多
目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本...目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本汤治疗。比较两组患者的临床疗效、不良反应发生率及治疗前后中医证候积分、肝功能指标[谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartateaminotransferase,AST)、γ-谷氨酰转肽酶(γ-GT)]、胆汁生化指标[总胆红素(total bilirubin,TBIL)、总胆汁酸(total bile acid,TBA)]。结果:两组患者发热、腹痛、黄疸等中医证候积分低于本组治疗前,且治疗后观察组低于对照组(P<0.05)。观察组有效率高于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后AST、ALT以及γ-GT低于本组治疗前,且治疗后观察组低于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后TBA高于本组治疗前,TBIL低于本组治疗前,且治疗后组间比较,差异具有统计学意义(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:扶正固本汤运用于胆总管结石手术后,能明显提高临床疗效,改善患者肝功能及胆汁生化指标,降低不良反应。展开更多
BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基...BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。展开更多
Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids(AAs),no D-AA should be found in natural products.This is not what is observed in the living w...Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids(AAs),no D-AA should be found in natural products.This is not what is observed in the living world.D-AAs are found in numerous natural compounds produced by bacteria,algae,fungi,or marine animals,and even vertebrates.A review of the literature indicated the existence of at least 132 peptide natural compounds in which D-AAs are an essential part of their structure.All compounds are listed,numbered and described herein.The two biosynthetic routes leading to the presence of D-AA in natural products are:non-ribosomal peptide synthesis(NRPS),and ribosomally synthesized and post-translationally modified peptide(RiPP)synthesis which are described.The methods used to identify the AA chirality within naturally occurring peptides are briefly discussed.The biological activity of an all-L synthetic peptide is most often completely different from that of the D-containing natural compounds.Analyzing the selected natural compounds showed that D-Ala,D-Val,D-Leu and D-Ser are the most commonly encountered D-AAs closely followed by the non-proteinogenic D-allo-Thr.D-Lys and D-Met were the least prevalent D-AAs in natu-rally occurring compounds.展开更多
In the present investigation, in vivo effects of purified ticks’ saliva toxin were evaluated on the level of certain important cellular metabolic enzymes i.e. acid phosphatase (ACP), alkaline phosphatase (ALP), gluta...In the present investigation, in vivo effects of purified ticks’ saliva toxin were evaluated on the level of certain important cellular metabolic enzymes i.e. acid phosphatase (ACP), alkaline phosphatase (ALP), glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and lactic dehydrogenase. For this purpose, sub-lethal doses, 40% and 80% of 24 h LD50 purified saliva toxins of Rhipicephalus microplus (Canestrini, 1888) were injected subcutaneously in the albino mice. In treated mice saliva toxins targeted membrane-bound enzymes i.e. serum acid phosphatase and alkaline phosphatase, its level was increased from 118.30% to 163.63% at the 6th hr in comparison to the control. Besides this, the levels of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) and lactic dehydrogenase (LDH) also increased up to 161.11% (at 6th hr), 148.27 (at 8th hr) and 125.45% (at 6th hr) respectively in comparison to control. An increase in the level of LDH showed insufficient oxygen supply, massive disintegration of cells and leakage of the enzyme into the circulation. It clearly indicated the toxic effects of saliva toxins on the membrane of blood cells, hepatocytes and myocardial muscle cell functions in albino mice. On the other hand activity of acetyl cholinesterase was reduced by 65.51% at the 6th hr of the saliva toxin injection in comparison to the control. This inhibition of acetyl cholinesterase activity caused the accumulation of acetylcholine molecules at the synaptic junctions and led to prolonged activation of acetylcholine receptors. It caused permanent stimulation of nerves and muscle cells that may result in muscular paralysis and finally death of the animal.展开更多
In the present, investigation effects of sub-lethal dose of purified paper wasp Ropalidia marginata venom toxins were evaluated on important metabolic enzymes i.e. ALP ACP, GPT, GOT, LDH, and AchE enzyme activity in s...In the present, investigation effects of sub-lethal dose of purified paper wasp Ropalidia marginata venom toxins were evaluated on important metabolic enzymes i.e. ALP ACP, GPT, GOT, LDH, and AchE enzyme activity in serum, liver, and gastrocnemius muscles of albino mice. Alkaline phosphatase was found to be increased up to 119.9% at the 6<sup>th</sup> hr of the toxin injection in comparison to control. This elevation may be due to cytolysis. Maximum increase i.e., 153.33% level of glutamate pyruvate transaminase (GPT) was found at 6 hrs of 40% of 24-h LD<sub>50</sub> treatment while it was found to be 151.1% at 6 hrs of 24 hr 80% of LD<sub>50</sub>, venom injection. A significant elevation was observed in LDH activity in serum, liver, and muscles, while the activity of AchE was decreased in serum, liver, and gastrocnemius muscles of albino mice after injecting the sub-lethal dose of Ropalidia marginata venom. This increase in the activity of LDH produces liver damage, massive disintegration and necrosis of hepatic cells. This elevation in LDH level led to a significant increase in the glucose catabolism and elevated oxidative stress in muscle and liver cells. It also displays insufficient oxygen supply and consequently leads to cell death. In experimental animals, venom toxin treatment decreased AchE level, and animals showed muscular paralysis. When mice were treated with 40% and 80% of 24-h LD<sub>50</sub> of purified venom caused a significant (p < 0.05) elevation in the level of ACP, GOT, GPT, and LDH while the reduction in ALP and AChE level. Present study will be useful in the development of prototypes for study of pharmacological and therapeutic effects of various venom toxins. For this purpose structure activity relationship of enzyme and venom toxin, its due interaction to various metabolic enzymes and receptors must be explored.展开更多
基金Supported by Natural Science Foundation of Sichuan Province,No.2023NSFSC0729Wu Jieping Foundation Special Fund for Clinical Research,No.320.6750.2022-19-100+1 种基金Foundation of Key Clinical Specialty of Sichuan Province,No.2022School Foundation of Chengdu Medical College,No.CYZYB21-05.
文摘BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.
文摘AIM:To examine whether a dose-up to 900 mg of ursodeoxycholic acid(UDCA) decreases transaminases in hepatitis C patients.METHODS:From January to December 2007,patients with chronic hepatitis C or compensated liver cirrhosis with hepatitis C virus(HCV)(43-80 years old) showing positive serum HCV-RNA who had already taken 600 mg/d of UDCA were recruited into this study.Blood parameters were examined at 4,8 and 24 wk after increasing the dose of oral UDCA from 600 to 900 mg/d.RESULTS:Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT) levels were signifi cantly decreased following the administration of 900 mg/d as compared to 600 mg/d.The decrease in ALT from immediately before the dose-up of UDCA to 8 wk after the dose-up was 14.3 IU/L,while that for AST was 10.5 IU/L and for GGT was 9.8 IU/L.Platelet count tended to increase after the dose-up of UDCA,although it did not show a statistically signifi cant level(P=0.05).Minor adverse events were observed in 3 cases,although no drop-outs from the study occurred.CONCLUSION:Oral administration of 900 mg/d of UDCA was more effective than 600 mg/d for reducing ALT,AST,and GGT levels in patients with HCV-related chronic liver disease.
文摘Irritable bowel syndrome(IBS)is an important health care concern.Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS.Some dietary intake could contribute to produce various metabolites including Damino acids by the fermentation by the gut microbiota.D-amino acids are the enantiomeric counterparts of L-amino acids,in general,which could play key roles in cellular physiological processes against various oxidative stresses.Therefore,the presence of D-amino acids has been shown to be linked to the protection of several organs in the body.In particular,the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids.Here,we would like to shed light on the roles of D-amino acids,which could be used for the treatment of IBS.
基金supported by the National Natural Science Foundation of China(Nos.21776233 and 22078273)National Key Research and Development Program(No.2022YFA0912000).
文摘Immobilization of D-amino acid dehydrogenase(DAADH)by the assembly of peptide linker was studied for the biosynthesis of Dphenylalanine.Hybrid material of zeolitic imidazolate framework-8(ZIF-8)combined with reduced graphene oxide(RGO)was applied for the immobilization of DAADH from Ureibacillus thermosphaericus.The recovery rate of DAADH/ZIF-8/RGO was 165.6%.DAADH/ZIF-8/RGO remained 53.4%of its initial activity at 50°C for 10 h while the free enzyme was inactivated.DAADH/ZIF-8/RGO maintained 70.5%activity in hyperalkaline solution with pH 12.Kinetic parameters indicated that DAADH/ZIF-8/RGO had greater affinity of phenylpyruvate as V_(max)/K_(m)of DAADH/ZIF-8/RGO was 1.27-fold than free enzyme.After seven recycles,the activity of DAADH/ZIF-8/RGO remained 64.3%.Furthermore,one-step separation and in situ immobilization of DAADH by ZIF-8/RGO/Ni was carried out with 1.5-fold activity enhancement.Combining peptide linker and metal-organic framework(MOF)immobilization,thermostability and activity of the immobilized DAADH were significantly improved.
文摘目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本汤治疗。比较两组患者的临床疗效、不良反应发生率及治疗前后中医证候积分、肝功能指标[谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartateaminotransferase,AST)、γ-谷氨酰转肽酶(γ-GT)]、胆汁生化指标[总胆红素(total bilirubin,TBIL)、总胆汁酸(total bile acid,TBA)]。结果:两组患者发热、腹痛、黄疸等中医证候积分低于本组治疗前,且治疗后观察组低于对照组(P<0.05)。观察组有效率高于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后AST、ALT以及γ-GT低于本组治疗前,且治疗后观察组低于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后TBA高于本组治疗前,TBIL低于本组治疗前,且治疗后组间比较,差异具有统计学意义(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:扶正固本汤运用于胆总管结石手术后,能明显提高临床疗效,改善患者肝功能及胆汁生化指标,降低不良反应。
文摘BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。
文摘Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids(AAs),no D-AA should be found in natural products.This is not what is observed in the living world.D-AAs are found in numerous natural compounds produced by bacteria,algae,fungi,or marine animals,and even vertebrates.A review of the literature indicated the existence of at least 132 peptide natural compounds in which D-AAs are an essential part of their structure.All compounds are listed,numbered and described herein.The two biosynthetic routes leading to the presence of D-AA in natural products are:non-ribosomal peptide synthesis(NRPS),and ribosomally synthesized and post-translationally modified peptide(RiPP)synthesis which are described.The methods used to identify the AA chirality within naturally occurring peptides are briefly discussed.The biological activity of an all-L synthetic peptide is most often completely different from that of the D-containing natural compounds.Analyzing the selected natural compounds showed that D-Ala,D-Val,D-Leu and D-Ser are the most commonly encountered D-AAs closely followed by the non-proteinogenic D-allo-Thr.D-Lys and D-Met were the least prevalent D-AAs in natu-rally occurring compounds.
文摘In the present investigation, in vivo effects of purified ticks’ saliva toxin were evaluated on the level of certain important cellular metabolic enzymes i.e. acid phosphatase (ACP), alkaline phosphatase (ALP), glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and lactic dehydrogenase. For this purpose, sub-lethal doses, 40% and 80% of 24 h LD50 purified saliva toxins of Rhipicephalus microplus (Canestrini, 1888) were injected subcutaneously in the albino mice. In treated mice saliva toxins targeted membrane-bound enzymes i.e. serum acid phosphatase and alkaline phosphatase, its level was increased from 118.30% to 163.63% at the 6th hr in comparison to the control. Besides this, the levels of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) and lactic dehydrogenase (LDH) also increased up to 161.11% (at 6th hr), 148.27 (at 8th hr) and 125.45% (at 6th hr) respectively in comparison to control. An increase in the level of LDH showed insufficient oxygen supply, massive disintegration of cells and leakage of the enzyme into the circulation. It clearly indicated the toxic effects of saliva toxins on the membrane of blood cells, hepatocytes and myocardial muscle cell functions in albino mice. On the other hand activity of acetyl cholinesterase was reduced by 65.51% at the 6th hr of the saliva toxin injection in comparison to the control. This inhibition of acetyl cholinesterase activity caused the accumulation of acetylcholine molecules at the synaptic junctions and led to prolonged activation of acetylcholine receptors. It caused permanent stimulation of nerves and muscle cells that may result in muscular paralysis and finally death of the animal.
文摘In the present, investigation effects of sub-lethal dose of purified paper wasp Ropalidia marginata venom toxins were evaluated on important metabolic enzymes i.e. ALP ACP, GPT, GOT, LDH, and AchE enzyme activity in serum, liver, and gastrocnemius muscles of albino mice. Alkaline phosphatase was found to be increased up to 119.9% at the 6<sup>th</sup> hr of the toxin injection in comparison to control. This elevation may be due to cytolysis. Maximum increase i.e., 153.33% level of glutamate pyruvate transaminase (GPT) was found at 6 hrs of 40% of 24-h LD<sub>50</sub> treatment while it was found to be 151.1% at 6 hrs of 24 hr 80% of LD<sub>50</sub>, venom injection. A significant elevation was observed in LDH activity in serum, liver, and muscles, while the activity of AchE was decreased in serum, liver, and gastrocnemius muscles of albino mice after injecting the sub-lethal dose of Ropalidia marginata venom. This increase in the activity of LDH produces liver damage, massive disintegration and necrosis of hepatic cells. This elevation in LDH level led to a significant increase in the glucose catabolism and elevated oxidative stress in muscle and liver cells. It also displays insufficient oxygen supply and consequently leads to cell death. In experimental animals, venom toxin treatment decreased AchE level, and animals showed muscular paralysis. When mice were treated with 40% and 80% of 24-h LD<sub>50</sub> of purified venom caused a significant (p < 0.05) elevation in the level of ACP, GOT, GPT, and LDH while the reduction in ALP and AChE level. Present study will be useful in the development of prototypes for study of pharmacological and therapeutic effects of various venom toxins. For this purpose structure activity relationship of enzyme and venom toxin, its due interaction to various metabolic enzymes and receptors must be explored.