BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between...BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.展开更多
Calix[n]arenes was utilized to detect PABA,the primary sunscreen component.This study investigates the interaction of calix[4]arene(C4),calix[6]arene(C6),and PABA using the Langmuir method and first-principle density ...Calix[n]arenes was utilized to detect PABA,the primary sunscreen component.This study investigates the interaction of calix[4]arene(C4),calix[6]arene(C6),and PABA using the Langmuir method and first-principle density functional theory(DFT).Using the Langmuir-Schaefer(LS)technique,an ultrathin film composed of calix[n]arenes and their complexes with PABA was deposited on various substrates.Based on the Langmuir study,the PABA molecule was bonded to the lower rims of both C4 and C6 with the host-guest ratio of 1:1.All of the LS films formed were then characterized by ultravioletvisible spectroscopy(UV-Vis),Fourier-transform infrared spectroscopy(FTIR)and carbon,hydrogen,nitrogen,sulfur elemental analyzer(CHNS).The band gap reduction obtained in the DFT study denotes the charge transfer interaction with promising reactivity between the calix[n]arenes and PABA.The sensing of PABA by C4 and C6 is successful based on the formation of bonding between them due to the hosts’effective trapping capacity.The outcomes of this study could be applied to drug delivery systems for future pharmaceutical and medical applications.展开更多
Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especiall...Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especially with respect to immu-nization coverage and linkage to care.The lack of governmental and public awar-eness regarding the long-term implications of hepatitis B burden cause under-funding of developmental projects.The presently approved treatment modalities have limited efficacy in complete viral eradication,hence the need for newer molecules to achieve functional cure(sustained undetectable hepatitis B surface antigen(HBsAg)and hepatitis B virus DNA in peripheral blood after a finite period of therapy).However,preliminary results from trials of novel therapies show their inadequacy to achieve this end by themselves but better performance with a low baseline serum HBsAg with nucleos(t)ide analogues(NA)treatment which need to be combined with/without pegylated interferon as an immu-nomodulator.Such therapy is limited by cost and adverse events and need to show incremental benefit over the standard of care(long-term NA therapy)with respect to efficacy and drug toxicities,making the development process tenuous.Thus,while such therapies continue to be tested,strategies should still focus on prevention of transmission by non-pharmaceutical measures,vaccination and increasing linkage to care.展开更多
●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were tre...●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.展开更多
Many approaches to neurodegenerative diseases that focus on amyloid-βclearance and gene therapy have not been successful.Some therapeutic applications focus on enhancing neuronal cell survival during the pathogenesis...Many approaches to neurodegenerative diseases that focus on amyloid-βclearance and gene therapy have not been successful.Some therapeutic applications focus on enhancing neuronal cell survival during the pathogenesis of neurodegenerative diseases,including mitochondrial dysfunction.Plasma membrane(PM)redox enzymes are crucial in maintaining cellular physiology and redox homeostasis in response to mitochondrial dysfunction.Neurohormetic phytochemicals are known to induce the expression of detoxifying enzymes under stress conditions.In this study,mechanisms of neuroprotective effects of 4-hydroxycinnamic acid(HCA)were examined by analyzing cell survival,levels of abnormal proteins,and mitochondrial functions in two different neuronal cells.HCA protected two neuronal cells exhibited high expression of PM redox enzymes and the consequent increase in the NAD^(+)/NADH ratio.Cells cultured with HCA showed delayed apoptosis and decreased oxidative/nitrative damage accompanied by decreased ROS production in the mitochondria.HCA increased the mitochondrial complexes I and II activities and ATP production.Also,HCA increased mitochondrial fusion and decreased mitochondrial fission.Overall,HCA maintains redox homeostasis and energy metabolism under oxidative/metabolic stress conditions.These findings suggest that HCA could be a promising therapeutic approach for neurodegenerative diseases.展开更多
基金Supported by The Health System Research Project of Ningxia Hui Autonomous Region of China,No.2022-NWKY-061.
文摘BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.
基金Funded by the Sultan Idris Education University(UPSI)(No.2020-0256-103-02(FRGS/1/2020/STG07/UPSI/02/2))provided by the Ministry of Higher Education,Malaysia。
文摘Calix[n]arenes was utilized to detect PABA,the primary sunscreen component.This study investigates the interaction of calix[4]arene(C4),calix[6]arene(C6),and PABA using the Langmuir method and first-principle density functional theory(DFT).Using the Langmuir-Schaefer(LS)technique,an ultrathin film composed of calix[n]arenes and their complexes with PABA was deposited on various substrates.Based on the Langmuir study,the PABA molecule was bonded to the lower rims of both C4 and C6 with the host-guest ratio of 1:1.All of the LS films formed were then characterized by ultravioletvisible spectroscopy(UV-Vis),Fourier-transform infrared spectroscopy(FTIR)and carbon,hydrogen,nitrogen,sulfur elemental analyzer(CHNS).The band gap reduction obtained in the DFT study denotes the charge transfer interaction with promising reactivity between the calix[n]arenes and PABA.The sensing of PABA by C4 and C6 is successful based on the formation of bonding between them due to the hosts’effective trapping capacity.The outcomes of this study could be applied to drug delivery systems for future pharmaceutical and medical applications.
文摘Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especially with respect to immu-nization coverage and linkage to care.The lack of governmental and public awar-eness regarding the long-term implications of hepatitis B burden cause under-funding of developmental projects.The presently approved treatment modalities have limited efficacy in complete viral eradication,hence the need for newer molecules to achieve functional cure(sustained undetectable hepatitis B surface antigen(HBsAg)and hepatitis B virus DNA in peripheral blood after a finite period of therapy).However,preliminary results from trials of novel therapies show their inadequacy to achieve this end by themselves but better performance with a low baseline serum HBsAg with nucleos(t)ide analogues(NA)treatment which need to be combined with/without pegylated interferon as an immu-nomodulator.Such therapy is limited by cost and adverse events and need to show incremental benefit over the standard of care(long-term NA therapy)with respect to efficacy and drug toxicities,making the development process tenuous.Thus,while such therapies continue to be tested,strategies should still focus on prevention of transmission by non-pharmaceutical measures,vaccination and increasing linkage to care.
基金Supported by the National Natural Science Foundation of China(No.81770889)Zhuhai Science and Technology Program(No.ZH22036201210134PWC).
文摘●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.
基金supported by the National Research Foundation of Korea(NRF)of the Korean Government(NRF-2021R1F1A1051212)by Logsynk Co.Ltd.(2-2021-1435-001).
文摘Many approaches to neurodegenerative diseases that focus on amyloid-βclearance and gene therapy have not been successful.Some therapeutic applications focus on enhancing neuronal cell survival during the pathogenesis of neurodegenerative diseases,including mitochondrial dysfunction.Plasma membrane(PM)redox enzymes are crucial in maintaining cellular physiology and redox homeostasis in response to mitochondrial dysfunction.Neurohormetic phytochemicals are known to induce the expression of detoxifying enzymes under stress conditions.In this study,mechanisms of neuroprotective effects of 4-hydroxycinnamic acid(HCA)were examined by analyzing cell survival,levels of abnormal proteins,and mitochondrial functions in two different neuronal cells.HCA protected two neuronal cells exhibited high expression of PM redox enzymes and the consequent increase in the NAD^(+)/NADH ratio.Cells cultured with HCA showed delayed apoptosis and decreased oxidative/nitrative damage accompanied by decreased ROS production in the mitochondria.HCA increased the mitochondrial complexes I and II activities and ATP production.Also,HCA increased mitochondrial fusion and decreased mitochondrial fission.Overall,HCA maintains redox homeostasis and energy metabolism under oxidative/metabolic stress conditions.These findings suggest that HCA could be a promising therapeutic approach for neurodegenerative diseases.
文摘目的分析体质量指数(Body mass index,BMI)与老年慢性心力衰竭(Chronic heart failure,CHF)患者血浆胱抑素C(cystatinC,Cys-C)、N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平相关性,并分析血浆Cys-C、NT-proBNP评估老年CHF患者预后价值。方法选择2021年7月—2022年10月在本院接受治疗的192例老年慢性心力衰竭(CHF)患者作为研究对象,按照BMI指数分为肥胖组(49例)、超重组(68例)和正常组(75例)三组。对比各亚组患者血浆Cys-C、NT-proBNP水平差异,采用Pearson相关性分析的方式探究老年CHF患者BMI指数与血浆Cys-C、NT-proBNP相关性,对入组患者实施12个月随访,将患者按照预后情况区分为死亡组和存活组,对比两亚组患者血浆Cys-C、NT-proBNP水平差异并评估预后评估价值。结果肥胖组患者血浆Cys-C、NT-proBNP水平高于超重组,超重组患者血浆Cys-C、NT-proBNP水平高于正常组,差异具有统计学意义(P<0.05);入组老年CHF患者的BMI指数与其血浆Cys-C、NT-proBN水平均呈现明显的正相关性(r=0.7104,P<0.0001)(r=0.6603,P<0.0001);随访12个月显示,死亡组患者的血浆Cys-C、NT-proBNP水平显著高于存活组患者,差异具有统计学意义(P<0.05);血浆Cys-C、NT-proBNP对老年CHF预后评估曲线下面积(area under curv,AUC)为0.6930(P=0.0009)、0.7982(P<0.0001)。结论老年CHF患者随BMI指数升高,血浆Cys-C、NT-proBNP水平逐渐升高,血浆Cys-C、NT-proBNP对老年CHF临床结局具有一定的预测价值,进一步研究有推广应用于老年CHF预后评估潜力。
