In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence t...In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence that activins,which are members of the transforming growth factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA subunits,is critically involved in the regulation of cell growth,apoptosis,and tissue architecture in the liver,while the hepatic function of other activins is largely unexplored so far.Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG,and at the cell membrane antagonistic coreceptors like Cripto or BAMBI.Additionally,in the intracellular space inhibitory Smads can modulate and control activin activity.Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation,fibrosis and development of cancer.The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.展开更多
BACKGROUND It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia(CAP)predictors.AIM To evaluate the association betwee...BACKGROUND It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia(CAP)predictors.AIM To evaluate the association between serum activin A levels and prognosis in CAP patients.METHODS A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition,and 48 healthy individuals as the control group were enrolled in this study.Circulating concentrations of activin A were measured using enzymelinked immunoassays.The interaction between activin A levels and etiologies of CAP was determined.Based on the severity of CAP,110 patients(65.48%)were categorized into group-I,42(25%)cases were grouped into group-II,and 16(9.52%)cases were categorized into group-III.RESULTS Serum activin A levels were higher in patients with CAP than controls,but independent of etiology.Moreover,the scores of Pneumonia Severity Index(PSI)and CURB-65 positively correlated with the increasing levels of serum activin A,and were at their highest peak in individuals in group-III(P<0.001).Combining activin A with CURB-65 or PSI was more effective in improving predictive property(P<0.01).According to Cox proportional regression analysis,after adjusting clinical parameters,we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients(P<0.001).CONCLUSION Higher level of serum activin A was associated with poor prognosis of CAP.Activin A can be used as a more valuable biomarker of prognosis in CAP patients.展开更多
BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-lik...BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.展开更多
Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studie...Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studies have demonstrated that these growth factors play multifaceted roles in regulating various functions in multiple organs,including the ovary.The spatial and temporal expression of inhibin subunits(a,bA,bB,and bC),their cognate receptors,and activin-binding proteins(inhibins and follistatins)in the principal cells of growing follicles in human ovaries indicates that these activin isoforms are involved in ovarian biology.Information collected from animal studies and clinical samples suggests that these locally produced growth factors are crucial modulators of various ovarian functions,including primordial germ cell development,follicular growth and development,ovarian steroidogenesis,extracellular matrix remodeling,oocyte maturation,ovulation,and luteal function.Along with gonadotropins,intrafollicular activins exert synergistic and complementary effects on growing follicles to help them develop a mature,competent oocyte that is prepared for fertilization.Abnormal activin expression,an imbalanced activin/follistatin ratio,and the dysregulation of the activin signaling pathway have been observed in several ovarian pathologies,such as reproductive aging,polycystic ovary syndrome,and ovarian cancers.Recent advancements in our understanding of the molecular interactions and mechanisms that underlie activins and the development of related ovarian abnormalities have provided insights into disease pathogenesis and increased opportunities to achieve efficient and safe therapies.展开更多
Among the avian species, understanding the roles of activin happen to be a dominant challenge in genetic evolution due to its complexity in nature. A case study of the activin gene in avian species was carried out usi...Among the avian species, understanding the roles of activin happen to be a dominant challenge in genetic evolution due to its complexity in nature. A case study of the activin gene in avian species was carried out using bioinformatics. As a sedentary bird, guinea fowl is more susceptible to local selection processes and needs a proper genetic study for conservation. The present study provides the basis for the use of activin or its target genes for the improvement of impaired wound healing, and activin antagonists for the prevention and treatment of fibrosis and the end of malignant tumors that over-express activin. The information provided will serve as a basic tool for broader genetic diversity studies to identify valuable poultry genetic resources and major genes for the development of breeding programs. This study was done by retrieving hundred (100) nucleotides and amino acid sequences of the activin gene belonging to guinea fowl and other avians from the GeneBank, aligning the sequences using BlastP determined the percent identity and phylogenetic relationship of the activin gene of guinea fowl and other avians. The shortest activin nucleotide sequence (467 bp) was observed in chicken and the longest (39896445 bp) in duck. Using the comparative sequence analysis, it was observed that the activin gene of chickens, turkeys and guinea fowl shared percent identity ranging from 91% to 95%. The percent identity reflects the degree of relatedness of species. Although closely related (90%) in ancestral line, the activin gene of guinea fowl and quail cannot be compared with guinea fowl-turkey (95%) nor guinea fowl-chicken (90%), in both biological functions and evolutionary relationship. Finally, the percent identity and similarity in function of the activin gene of guinea fowl, turkey, and chicken were in the range of 93% - 100%, indicating that the activin gene of avians possesses similar functions, well conserved and is very effective in performing functions like increasing FSH bindings, FSH-induced aromatization, improves wound healing and enhances scar formation, regulates morphogenesis of branching organs, and enhances ovarian folliculogenesis. The study, therefore, recommends farmers select and breed for activin genes in order to promote reproductive efficiency, thereby barricading species extinction.展开更多
AIM: To examine the expression of activin A, a member of the transforming growth factor (TGFbeta) superfamily, recently has been reported to be overexpressed in liver cirrhosis, in the course of carbon tetrachloride-i...AIM: To examine the expression of activin A, a member of the transforming growth factor (TGFbeta) superfamily, recently has been reported to be overexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enhanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 +/- 0.094 vs 0.2860.0670, P【 0.01; 0.620 +/- 0.134 vs 0.286 +/- 0670, P【 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas. CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period.展开更多
文摘In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence that activins,which are members of the transforming growth factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA subunits,is critically involved in the regulation of cell growth,apoptosis,and tissue architecture in the liver,while the hepatic function of other activins is largely unexplored so far.Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG,and at the cell membrane antagonistic coreceptors like Cripto or BAMBI.Additionally,in the intracellular space inhibitory Smads can modulate and control activin activity.Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation,fibrosis and development of cancer.The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.
基金This study was approved by the ethical committee of Yixing People’s Hospital(Approval No.2018-036).
文摘BACKGROUND It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia(CAP)predictors.AIM To evaluate the association between serum activin A levels and prognosis in CAP patients.METHODS A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition,and 48 healthy individuals as the control group were enrolled in this study.Circulating concentrations of activin A were measured using enzymelinked immunoassays.The interaction between activin A levels and etiologies of CAP was determined.Based on the severity of CAP,110 patients(65.48%)were categorized into group-I,42(25%)cases were grouped into group-II,and 16(9.52%)cases were categorized into group-III.RESULTS Serum activin A levels were higher in patients with CAP than controls,but independent of etiology.Moreover,the scores of Pneumonia Severity Index(PSI)and CURB-65 positively correlated with the increasing levels of serum activin A,and were at their highest peak in individuals in group-III(P<0.001).Combining activin A with CURB-65 or PSI was more effective in improving predictive property(P<0.01).According to Cox proportional regression analysis,after adjusting clinical parameters,we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients(P<0.001).CONCLUSION Higher level of serum activin A was associated with poor prognosis of CAP.Activin A can be used as a more valuable biomarker of prognosis in CAP patients.
基金Supported by the Science and Technology Research Foundation of Guizhou Province,No.QKHJC-ZK[2022]YB642Science and Technology Research Foundation of Hubei Province,No.2022BCE030+2 种基金Science and Technology Research Foundation of Zunyi City,No.ZSKH-HZ(2022)344Research Project on Traditional Chinese Medicine and Ethnic Medicine Science and Technology of Guizhou Provincial Administration of Traditional Chinese Medicine,No.QZYY-2023-021Science and Technology Research Foundation of Bijie City,No.BKH[2022]8.
文摘BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.
基金This work was supported by the Foundation Scheme Grant FDN-143317 to PCKL.
文摘Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studies have demonstrated that these growth factors play multifaceted roles in regulating various functions in multiple organs,including the ovary.The spatial and temporal expression of inhibin subunits(a,bA,bB,and bC),their cognate receptors,and activin-binding proteins(inhibins and follistatins)in the principal cells of growing follicles in human ovaries indicates that these activin isoforms are involved in ovarian biology.Information collected from animal studies and clinical samples suggests that these locally produced growth factors are crucial modulators of various ovarian functions,including primordial germ cell development,follicular growth and development,ovarian steroidogenesis,extracellular matrix remodeling,oocyte maturation,ovulation,and luteal function.Along with gonadotropins,intrafollicular activins exert synergistic and complementary effects on growing follicles to help them develop a mature,competent oocyte that is prepared for fertilization.Abnormal activin expression,an imbalanced activin/follistatin ratio,and the dysregulation of the activin signaling pathway have been observed in several ovarian pathologies,such as reproductive aging,polycystic ovary syndrome,and ovarian cancers.Recent advancements in our understanding of the molecular interactions and mechanisms that underlie activins and the development of related ovarian abnormalities have provided insights into disease pathogenesis and increased opportunities to achieve efficient and safe therapies.
文摘Among the avian species, understanding the roles of activin happen to be a dominant challenge in genetic evolution due to its complexity in nature. A case study of the activin gene in avian species was carried out using bioinformatics. As a sedentary bird, guinea fowl is more susceptible to local selection processes and needs a proper genetic study for conservation. The present study provides the basis for the use of activin or its target genes for the improvement of impaired wound healing, and activin antagonists for the prevention and treatment of fibrosis and the end of malignant tumors that over-express activin. The information provided will serve as a basic tool for broader genetic diversity studies to identify valuable poultry genetic resources and major genes for the development of breeding programs. This study was done by retrieving hundred (100) nucleotides and amino acid sequences of the activin gene belonging to guinea fowl and other avians from the GeneBank, aligning the sequences using BlastP determined the percent identity and phylogenetic relationship of the activin gene of guinea fowl and other avians. The shortest activin nucleotide sequence (467 bp) was observed in chicken and the longest (39896445 bp) in duck. Using the comparative sequence analysis, it was observed that the activin gene of chickens, turkeys and guinea fowl shared percent identity ranging from 91% to 95%. The percent identity reflects the degree of relatedness of species. Although closely related (90%) in ancestral line, the activin gene of guinea fowl and quail cannot be compared with guinea fowl-turkey (95%) nor guinea fowl-chicken (90%), in both biological functions and evolutionary relationship. Finally, the percent identity and similarity in function of the activin gene of guinea fowl, turkey, and chicken were in the range of 93% - 100%, indicating that the activin gene of avians possesses similar functions, well conserved and is very effective in performing functions like increasing FSH bindings, FSH-induced aromatization, improves wound healing and enhances scar formation, regulates morphogenesis of branching organs, and enhances ovarian folliculogenesis. The study, therefore, recommends farmers select and breed for activin genes in order to promote reproductive efficiency, thereby barricading species extinction.
文摘AIM: To examine the expression of activin A, a member of the transforming growth factor (TGFbeta) superfamily, recently has been reported to be overexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enhanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 +/- 0.094 vs 0.2860.0670, P【 0.01; 0.620 +/- 0.134 vs 0.286 +/- 0670, P【 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas. CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period.
