BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
Pasteurellosis is the most prevalent, extremely contagious bacterial disease among domestic rabbits and is considered the leading cause of deaths in rabbits, resulting in enormous economic losses to the rabbit industr...Pasteurellosis is the most prevalent, extremely contagious bacterial disease among domestic rabbits and is considered the leading cause of deaths in rabbits, resulting in enormous economic losses to the rabbit industry. Screening for bacterial agents causing mortalities in rabbits revealed the presence of Enterobacteriacae species in approximately 42% of studied cases, with E. coli the most commonly isolated organism. The present study was designed to evaluate the immune response of rabbits vaccinated with a locally prepared, combined inactivated vaccine of Pasteurella multocida and E. coli, adjuvanated with Montanide ISA70. A total of 370 rabbits, aged 2 - 3 weeks, were divided into four groups: (G1) vaccinated with a polyvalent P. multocida vaccine, (G2) vaccinated with a polyvalent E. coli vaccine, (G3) vaccinated with a combined inactivated Montanide ISA70 vaccine of P. multocida and E. coli, and (G4) kept as a non-vaccinated control group. All rabbits received two doses of 0.5 ml of the prepared vaccines, administered one month apart, and were then challenged with virulent strains of P. multocida and E. coli three weeks after the second vaccination. The prepared vaccines were evaluated by determining humoral immunity using indirect haemagglutination (IHA) test and ELISA. The potency of the vaccines was assessed through challenge and determination of LD50. Experimental findings on the prepared polyvalent combined inactivated P. multocida and E. coli vaccine indicated that it is a potent vaccine, producing the highest antibody titers and a 90% protection rate against challenges with virulent strains of P. multocida type A, D2, and E. coli types O157, O151 and O125. Thus, this vaccine is promising in addressing both P. multocida and E. coli problems in rabbits, farms, providing significant protection, and we recommend its commercial production to help rabbit producers control these two major bacterial infections.展开更多
Aqueous zinc metal batteries(AZMBs)have garnered widespread attention due to their low cost and high safety.However,current researches are still primarily focused on reversible cycling at low areal capacity,which is f...Aqueous zinc metal batteries(AZMBs)have garnered widespread attention due to their low cost and high safety.However,current researches are still primarily focused on reversible cycling at low areal capacity,which is far from practical application.Addressing interfacial stability issues encountered during cycling and employing interfacial optimization strategies can promote the development of safe and eco-friendly AZMBs.By introducingγ-valerolactone(GVL),which disrupts the original hydrogen bonding network of water,the electrochemical window of electrolyte is expanded,and the reactivity of water is significantly reduced.Additionally,the incorporation of GVL in Zn ion solvation alters the deposition pattern on the Zn anode surface,resulting in improved cyclic performance.The cells demonstrated excellent performance,maintaining stable over 400 h at 5 mA/cm^(2)-5 mA·h/cm^(2),and nearly 300 h in Zn||Zn symmetric cell at 80%depth of discharge(DOD).The full cells matched with NH_(4)V_(4)O_(10) could cycle over 200 cycles under the condition of high areal capacity(7 mA·h/cm^(2)),an N/P ratio of 1.99 and an E/C ratio of 9.3μL/(mA·h).展开更多
Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic ac...Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.展开更多
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
文摘Pasteurellosis is the most prevalent, extremely contagious bacterial disease among domestic rabbits and is considered the leading cause of deaths in rabbits, resulting in enormous economic losses to the rabbit industry. Screening for bacterial agents causing mortalities in rabbits revealed the presence of Enterobacteriacae species in approximately 42% of studied cases, with E. coli the most commonly isolated organism. The present study was designed to evaluate the immune response of rabbits vaccinated with a locally prepared, combined inactivated vaccine of Pasteurella multocida and E. coli, adjuvanated with Montanide ISA70. A total of 370 rabbits, aged 2 - 3 weeks, were divided into four groups: (G1) vaccinated with a polyvalent P. multocida vaccine, (G2) vaccinated with a polyvalent E. coli vaccine, (G3) vaccinated with a combined inactivated Montanide ISA70 vaccine of P. multocida and E. coli, and (G4) kept as a non-vaccinated control group. All rabbits received two doses of 0.5 ml of the prepared vaccines, administered one month apart, and were then challenged with virulent strains of P. multocida and E. coli three weeks after the second vaccination. The prepared vaccines were evaluated by determining humoral immunity using indirect haemagglutination (IHA) test and ELISA. The potency of the vaccines was assessed through challenge and determination of LD50. Experimental findings on the prepared polyvalent combined inactivated P. multocida and E. coli vaccine indicated that it is a potent vaccine, producing the highest antibody titers and a 90% protection rate against challenges with virulent strains of P. multocida type A, D2, and E. coli types O157, O151 and O125. Thus, this vaccine is promising in addressing both P. multocida and E. coli problems in rabbits, farms, providing significant protection, and we recommend its commercial production to help rabbit producers control these two major bacterial infections.
基金Project(2023YFC2908305)supported by the National Key R&D Program of ChinaProjects(52072411,52301273)supported by the National Natural Science Foundation of China+1 种基金Project(2023CXQD038)supported by the Central South University Innovation-Driven Research Program,ChinaProject(S202310533413)supported by the Fundamental Research Funds for the Central Universities of Central South University,China。
文摘Aqueous zinc metal batteries(AZMBs)have garnered widespread attention due to their low cost and high safety.However,current researches are still primarily focused on reversible cycling at low areal capacity,which is far from practical application.Addressing interfacial stability issues encountered during cycling and employing interfacial optimization strategies can promote the development of safe and eco-friendly AZMBs.By introducingγ-valerolactone(GVL),which disrupts the original hydrogen bonding network of water,the electrochemical window of electrolyte is expanded,and the reactivity of water is significantly reduced.Additionally,the incorporation of GVL in Zn ion solvation alters the deposition pattern on the Zn anode surface,resulting in improved cyclic performance.The cells demonstrated excellent performance,maintaining stable over 400 h at 5 mA/cm^(2)-5 mA·h/cm^(2),and nearly 300 h in Zn||Zn symmetric cell at 80%depth of discharge(DOD).The full cells matched with NH_(4)V_(4)O_(10) could cycle over 200 cycles under the condition of high areal capacity(7 mA·h/cm^(2)),an N/P ratio of 1.99 and an E/C ratio of 9.3μL/(mA·h).
基金financially supported by National Natural Science Foundation of China(81700524)Natural Science Foundation of Fujian Province(2022J01866)from Fujian Provincial Department of Science and Technology+1 种基金Key Project of Fujian University of Traditional Chinese Medicine(X2021019)Collaborative Innovation and Platform Establishment Project of Department of Science and Technology of Guangdong Province(2019A050520003)。
文摘Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.
