BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported m...BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported mutations that associate with complete TBG deficiency(TBG-CD).Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family.CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine,free triiodothyronine,thyrotropin,but lower total thyroxine and total triiodothyronine,and undetectable serum TBG,indicative of TBG-CD.Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated.Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s).Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly(L283F)among 117 Chinese men.A novel mutation of TBG(p.Phe135Alafs*21),a 19-nucleotide insertion in exon 1,was identified,which resulted in a truncated TBG protein product and caused TBG-CD.The other mutation,identified in the proband’s father,is a known polymorphism,TBG-Poly(L283F).The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%.CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family.Additionally,it was found that 21.37%of Chinese males had TBG-Poly(L283F).展开更多
Objective: The objective is to explore the mechanism of inhibitory effect of three main SCFAs (acetate, propionate and butyrate) on inflammatory response of A549 cells. Methods: Human lung adenocarcinoma cells (A549 c...Objective: The objective is to explore the mechanism of inhibitory effect of three main SCFAs (acetate, propionate and butyrate) on inflammatory response of A549 cells. Methods: Human lung adenocarcinoma cells (A549 cells) were cultured, and were divided into normal control group (NC group), A. baumannii infection group (A. baumannii group), NF-κB inhibitor group (JSH group), A. baumannii infection + sodium acetate group (NaAc group), A. baumannii infection + sodium propionate group (NaPc group) and A. baumannii infection + sodium butyrate group (NaB group). Real-time quantitative PCR was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, IL-6, and TGF-β in A549 cells. Western blotting assay was used to determine the expression of autophagy and “pyroptosis” related proteins of NRLP3, cleaved-Caspase-1 (P20), GSDMD (P30), LC-3 and Beclin-1. At the same time, the expression of NF-κB p65 protein in nucleus and cytoplasm of A549 cells was detected. The level of reactive oxygen species in A549 cells was detected by flow cytometry. Results: Compared with A. baumannii group, the mRNA expression of NLRP3, IL-1β and IL-6 in NaAc group, NaPc group and NaB group decreased significantly, the mRNA expression of Caspase-1 in NaPc group and NaB group decreased significantly, only the mRNA expression of TGF-β in NaB group increased significantly;LC3-II expression increased significantly in NaPc group and NaB group, only Beclin-1 expression increased and GSDMD (p30) expression decreased significantly in NaB group. All three kinds of SCFAs could significantly inhibit the expression of cleaved-Caspase-1 (p20) after A. baumannii infection, but there was no significant change in the protein expression of NLRP3. Compared with NC group, the production of reactive oxygen species in A. baumannii group increased significantly at 3 h after A. baumannii infection. Compared with A. baumannii group, NaB could significantly suppress the production of reactive oxygen species induced by A. baumannii. Compared with A. baumannii group, the expression of NF-κB p65 in nucleus was significantly decreased and the expression of NF-κB p65 in cytoplasm was significantly increased after 24 h pre-incubation with NaB, NaPc and NaAc, respectively. Conclusion: A. baumannii can induce inflammatory injury of pulmonary epithelial cells, and the three major SCFAs can inhibit the activation of NLRP3 inflammasome and the release of pro-inflammatory factors through NF-κB/ROS/NLRP3 pathway, which provides a new way for clinical prevention of severe inflammatory injury caused by A. baumannii infection.展开更多
Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic ...Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied.In this investigation,we established mouse models of depression using aversive stimuli including exposure to fox urine,air puff and foot shock and physical restraint.Concurrently,we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days.Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxietylike behaviors evaluated using the open field test.In addition,aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula.Importantly,concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes.These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula.The study was approved by the Jinan University Institutional Animal Care and Use Committee(approval No.20170301003)on March 1,2017.展开更多
Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardia...Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardial infarction(MI)by inducing angiogenesis.Methods:Male,adult Sprague-Dawley rats were randomly divided into 5 groups(n=12 in each group):sham group(S),sedentary MI group(MI),MI+resistance exercise group(MR),MI+adeno-associated virus(AAV)-FSTL1 injection group(MA),and MI+AAV-FSTL1 injection+resistance exercise group(MAR).The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle.The MI model was established by ligation of the left anterior descending coronary artery.Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder.Heart function was evaluated by hemodynamic measures.Collagen volume fraction of myocardium was observed and analyzed by Masson’s staining.Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-b receptor 1(TGFbR1)inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1.Angiogenesis,cell proliferation,and disco interacting protein 2 homolog A(DIP2A)location were observed by immunofluorescence staining.The expression of FSTL1,DIP2A,and the activation of signaling pathways were detected by Western blotting.Angiogenesis of endothelial cells was observed by tubule experiment.One-way analysis of variance and Student’s t test were used for statistical analysis.Results:Resistance exercise stimulated the secretion of skeletal muscle FSTL1,which promoted myocardial angiogenesis,inhibited pathological remodeling,and protected cardiac function in MI rats.Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart.Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A,while TGFbR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A,which was not conducive to angiogenesis.FSTL1 bound to the receptor,DIP2A,to regulate angiogenesis mainly through the Smad2/3 signaling pathway.FSTL1-DIP2A directly activated Smad2/3 and was not affected by TGFbR1.Conclusion:Dynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1,which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A-Smad2/3 signaling pathway in MI rats.展开更多
The prevalence of diabetes has increased rapidly throughout the world in recent years.Currently,approximately 463 million people are living with diabetes,and the number has tripled over the last two decades.Here,we de...The prevalence of diabetes has increased rapidly throughout the world in recent years.Currently,approximately 463 million people are living with diabetes,and the number has tripled over the last two decades.Here,we describe the global epidemiology of diabetes in 2019 and forecast the trends to 2030 and 2045 in China,India,USA,and the globally.The gut microbiota plays a major role in metabolic diseases,especially diabetes.In this review,we describe the interaction between diabetes and gut microbiota in three aspects:probiotics,antidiabetic medication,and diet.Recent findings indicate that probiotics,antidiabetic medications,or dietary interventions treat diabetes by shifting the gut microbiome,particularly by raising beneficial bacteria and reducing harmful bacteria.We conclude that targeting the gut microbiota is becoming a novel therapeutic strategy for diabetes.展开更多
基金Supported by the National Natural Science Foundation of China,No.81570711National Clinical Key College Fund and the Key Platform Foundation of Science and Technology for the Universities in Liaoning Province,No.16010
文摘BACKGROUND Thyroxine-binding globulin(TBG;the gene product of SERPINA7)is the main transporter of thyroid hormones in humans.Mutations in the TBG gene may lead to inherited TBG deficiency.There have been 28 reported mutations that associate with complete TBG deficiency(TBG-CD).Here we identified a novel frameshift mutation causing early termination of the TBG protein and TBG-CD in a Chinese family.CASE SUMMARY A 46-year-old Chinese man was referred to our hospital with normal free thyroxine,free triiodothyronine,thyrotropin,but lower total thyroxine and total triiodothyronine,and undetectable serum TBG,indicative of TBG-CD.Blood samples were obtained from the patient’s family members and thyroid function and serum TBG were evaluated.Genomic DNA from peripheral blood was sequenced to detect possible TBG mutation(s).Quantitative PCR high-resolution melting curve analysis was used to screen TBG-Poly(L283F)among 117 Chinese men.A novel mutation of TBG(p.Phe135Alafs*21),a 19-nucleotide insertion in exon 1,was identified,which resulted in a truncated TBG protein product and caused TBG-CD.The other mutation,identified in the proband’s father,is a known polymorphism,TBG-Poly(L283F).The frequency of the TBG-Poly allele among 117 unrelated Han Chinese men from northeast China was 21.37%.CONCLUSION A novel mutation in the TBG gene associated with the TBG-CD phenotype was identified in a Chinese family.Additionally,it was found that 21.37%of Chinese males had TBG-Poly(L283F).
文摘Objective: The objective is to explore the mechanism of inhibitory effect of three main SCFAs (acetate, propionate and butyrate) on inflammatory response of A549 cells. Methods: Human lung adenocarcinoma cells (A549 cells) were cultured, and were divided into normal control group (NC group), A. baumannii infection group (A. baumannii group), NF-κB inhibitor group (JSH group), A. baumannii infection + sodium acetate group (NaAc group), A. baumannii infection + sodium propionate group (NaPc group) and A. baumannii infection + sodium butyrate group (NaB group). Real-time quantitative PCR was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, IL-6, and TGF-β in A549 cells. Western blotting assay was used to determine the expression of autophagy and “pyroptosis” related proteins of NRLP3, cleaved-Caspase-1 (P20), GSDMD (P30), LC-3 and Beclin-1. At the same time, the expression of NF-κB p65 protein in nucleus and cytoplasm of A549 cells was detected. The level of reactive oxygen species in A549 cells was detected by flow cytometry. Results: Compared with A. baumannii group, the mRNA expression of NLRP3, IL-1β and IL-6 in NaAc group, NaPc group and NaB group decreased significantly, the mRNA expression of Caspase-1 in NaPc group and NaB group decreased significantly, only the mRNA expression of TGF-β in NaB group increased significantly;LC3-II expression increased significantly in NaPc group and NaB group, only Beclin-1 expression increased and GSDMD (p30) expression decreased significantly in NaB group. All three kinds of SCFAs could significantly inhibit the expression of cleaved-Caspase-1 (p20) after A. baumannii infection, but there was no significant change in the protein expression of NLRP3. Compared with NC group, the production of reactive oxygen species in A. baumannii group increased significantly at 3 h after A. baumannii infection. Compared with A. baumannii group, NaB could significantly suppress the production of reactive oxygen species induced by A. baumannii. Compared with A. baumannii group, the expression of NF-κB p65 in nucleus was significantly decreased and the expression of NF-κB p65 in cytoplasm was significantly increased after 24 h pre-incubation with NaB, NaPc and NaAc, respectively. Conclusion: A. baumannii can induce inflammatory injury of pulmonary epithelial cells, and the three major SCFAs can inhibit the activation of NLRP3 inflammasome and the release of pro-inflammatory factors through NF-κB/ROS/NLRP3 pathway, which provides a new way for clinical prevention of severe inflammatory injury caused by A. baumannii infection.
基金supported by the National Natural Science Foundation of China,Nos.31900825(to SL),31922030(to CRR),31771170(to CRR)Science and Technology Program of Guangdong Province of China,No.2018B030334001(to CRR)+3 种基金Science and Techology of Guangzhou of China,No.202007030012(to CRR)Guangdong Special Support Program of China,No.2017TQ04R173(to CRR)Pearl River S&T Nova Program of Guangzhou Province of China,No.201806010198(to CRR)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China,No.2018GZR110102002(to KFS)。
文摘Previous studies have shown that Lycium barbarum polysaccharide,the main active component of Lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied.In this investigation,we established mouse models of depression using aversive stimuli including exposure to fox urine,air puff and foot shock and physical restraint.Concurrently,we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days.Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxietylike behaviors evaluated using the open field test.In addition,aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula.Importantly,concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes.These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula.The study was approved by the Jinan University Institutional Animal Care and Use Committee(approval No.20170301003)on March 1,2017.
基金supported this research:The National Natural Science Foundation of China(No.31671240 to ZT,No.31900828 to YX).
文摘Purpose:The aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1(FSTL1),which may induce cardioprotection in rats following myocardial infarction(MI)by inducing angiogenesis.Methods:Male,adult Sprague-Dawley rats were randomly divided into 5 groups(n=12 in each group):sham group(S),sedentary MI group(MI),MI+resistance exercise group(MR),MI+adeno-associated virus(AAV)-FSTL1 injection group(MA),and MI+AAV-FSTL1 injection+resistance exercise group(MAR).The AAV-FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle.The MI model was established by ligation of the left anterior descending coronary artery.Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder.Heart function was evaluated by hemodynamic measures.Collagen volume fraction of myocardium was observed and analyzed by Masson’s staining.Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-b receptor 1(TGFbR1)inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1.Angiogenesis,cell proliferation,and disco interacting protein 2 homolog A(DIP2A)location were observed by immunofluorescence staining.The expression of FSTL1,DIP2A,and the activation of signaling pathways were detected by Western blotting.Angiogenesis of endothelial cells was observed by tubule experiment.One-way analysis of variance and Student’s t test were used for statistical analysis.Results:Resistance exercise stimulated the secretion of skeletal muscle FSTL1,which promoted myocardial angiogenesis,inhibited pathological remodeling,and protected cardiac function in MI rats.Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart.Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A,while TGFbR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A,which was not conducive to angiogenesis.FSTL1 bound to the receptor,DIP2A,to regulate angiogenesis mainly through the Smad2/3 signaling pathway.FSTL1-DIP2A directly activated Smad2/3 and was not affected by TGFbR1.Conclusion:Dynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1,which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A-Smad2/3 signaling pathway in MI rats.
基金Supported by Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology,Ministry of Education,No.201705.
文摘The prevalence of diabetes has increased rapidly throughout the world in recent years.Currently,approximately 463 million people are living with diabetes,and the number has tripled over the last two decades.Here,we describe the global epidemiology of diabetes in 2019 and forecast the trends to 2030 and 2045 in China,India,USA,and the globally.The gut microbiota plays a major role in metabolic diseases,especially diabetes.In this review,we describe the interaction between diabetes and gut microbiota in three aspects:probiotics,antidiabetic medication,and diet.Recent findings indicate that probiotics,antidiabetic medications,or dietary interventions treat diabetes by shifting the gut microbiome,particularly by raising beneficial bacteria and reducing harmful bacteria.We conclude that targeting the gut microbiota is becoming a novel therapeutic strategy for diabetes.
