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
Saline and hypersaline wetlands account for almost half of the volume of inland water globally.They provide pivotal habitat for a vast range of species,including crucial ecosystem services for humans such as carbon si...Saline and hypersaline wetlands account for almost half of the volume of inland water globally.They provide pivotal habitat for a vast range of species,including crucial ecosystem services for humans such as carbon sink storage and extractive resource reservoirs.Despite their importance,effective ecological assessment is in its infancy compared to current conventional surveys carried out in freshwater ecosystems.The integration of environmental DNA(eDNA)analysis and traditional techniques has the potential to transform biomonitoring processes,particularly in remote and understudied saline environments.In this context,this preliminary study aims to explore the potential of eDNA coupled with conventional approaches by targeting five hypersaline lakes at Rottnest Island(Wadjemup)in Western Australia.We focused on the invertebrate community,a widely accepted key ecological indicator to assess the conservational status in rivers and lakes.The combination of metabarcoding with morphology-based taxonomic analysis described 16 taxa belonging to the orders Anostraca,Diptera,Isopoda,and Coleoptera.DNA-based diversity assessment revealed more taxa at higher taxonomic resolution than the morphology-based taxonomic analysis.However,certain taxa(i.e.,Ephydridae,Stratyiomidae,Ceratopogonidae)were only identified via net surveying.Overall,our results indicate that great potential resides in combining conventional net-based surveys with novel eDNA approaches in saline and hypersaline lakes.Indeed,urgent and effective conservational frameworks are required to contrast the enormous pressure that these ecosystems are increasingly facing.Further investigations at larger spatial temporal scales will allow consolidation of robust,reliable,and affordable biomonitoring frameworks in the underexplored world of saline wetlands.展开更多
The rapid growth of distributed renewable energy penetration is promoting the evolution of the energy system toward decentralization and decentralized and digitized smart grids.This study was based on energy blockchai...The rapid growth of distributed renewable energy penetration is promoting the evolution of the energy system toward decentralization and decentralized and digitized smart grids.This study was based on energy blockchain,and developed a dual-biding mechanism based on the real-time energy surplus and demand in the local smart grid,which is expected to enable reliable,affordable,and clean energy supply in smart communities.In the proposed system,economic benefits could be achieved by replacing fossil-fuel-based electricity with the high penetration of affordable solar PV electricity.The reduction of energy surplus realized by distributed energy production and P2P energy trading,within the smart grid results in less transmission loss and lower requirements for costly upgrading of existing grids.By adopting energy blockchain and smart contract technologies,energy secure trading with a low risk of privacy leakage could be accommodated.The prototype is examined through a case study,and the feasibility and efficiency of the proposed mechanism are further validated by scenario analysis.展开更多
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
AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subject...AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.展开更多
The present paper is basically written as a non-apologetic strong defence of the thesis that computation is part and parcel of a physical theory and by no means a mere numerical evaluation of the prediction of a theor...The present paper is basically written as a non-apologetic strong defence of the thesis that computation is part and parcel of a physical theory and by no means a mere numerical evaluation of the prediction of a theory which comes towards the end. Various general considerations as well as specific examples are given to illustrate and support our arguments. These examples range from the practical aspect to almost esoteric considerations but at the end, everything converges towards a unity of theory and computation presented in the form of modern fractal logic and transfinite quantum field theory in a Cantorian spacetime. It is true that all our examples are taken from physics but our discussion is applicable in equal measure to a much wider aspect of life.展开更多
Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm...Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm﹣1. The band due to C-H band and called hydrocarbon band was found only in paralytic and Alzheimer diseased along with normal healthy controls. Carbide band (C=C) is found only in Duchenne muscular dystrophy, paralytic and Alzheimer’s disease patients. Amide I was intact in all disorders with normal persons. Peroxide band (O-O) was found in all the cases of study. Amide IV band was found in paralytic, muscular dystrophy, Alzheimer’s diseases and normal controls. The amide V band was found in Alzheimer’s diseases only. The appearance or disappearance of the bands is a good sign to understand the mechanisms at the molecular level. FTIR spectroscopy may help in the diagnosis of the disease at the early stage of the onset. This spectroscopy can be used nicely for the study of hair, vaginal fluid, nails, urine, mucus, semen, synovial fluid, blood, hemoproteins, skin, and tears for human beings. We can also use it to understand the effect of adulteration on food and paint technology. FTIR is an indicator to explore the changes occurring at molecular level.展开更多
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.
基金Supported by the Curtin-BHP alliance within the framework of the“eDNA for Global Environment Studies(eDGES)”program。
文摘Saline and hypersaline wetlands account for almost half of the volume of inland water globally.They provide pivotal habitat for a vast range of species,including crucial ecosystem services for humans such as carbon sink storage and extractive resource reservoirs.Despite their importance,effective ecological assessment is in its infancy compared to current conventional surveys carried out in freshwater ecosystems.The integration of environmental DNA(eDNA)analysis and traditional techniques has the potential to transform biomonitoring processes,particularly in remote and understudied saline environments.In this context,this preliminary study aims to explore the potential of eDNA coupled with conventional approaches by targeting five hypersaline lakes at Rottnest Island(Wadjemup)in Western Australia.We focused on the invertebrate community,a widely accepted key ecological indicator to assess the conservational status in rivers and lakes.The combination of metabarcoding with morphology-based taxonomic analysis described 16 taxa belonging to the orders Anostraca,Diptera,Isopoda,and Coleoptera.DNA-based diversity assessment revealed more taxa at higher taxonomic resolution than the morphology-based taxonomic analysis.However,certain taxa(i.e.,Ephydridae,Stratyiomidae,Ceratopogonidae)were only identified via net surveying.Overall,our results indicate that great potential resides in combining conventional net-based surveys with novel eDNA approaches in saline and hypersaline lakes.Indeed,urgent and effective conservational frameworks are required to contrast the enormous pressure that these ecosystems are increasingly facing.Further investigations at larger spatial temporal scales will allow consolidation of robust,reliable,and affordable biomonitoring frameworks in the underexplored world of saline wetlands.
基金Fundings that permitted this research were granted by Australia CRC for Low Carbon Living through the Project“Integrated Carbon Metrics(ICM)”(RP2007)the National Natural Science Foundation of China(51908064)the Natural Science Foundation of Hunan Province(2021JJ30717).
文摘The rapid growth of distributed renewable energy penetration is promoting the evolution of the energy system toward decentralization and decentralized and digitized smart grids.This study was based on energy blockchain,and developed a dual-biding mechanism based on the real-time energy surplus and demand in the local smart grid,which is expected to enable reliable,affordable,and clean energy supply in smart communities.In the proposed system,economic benefits could be achieved by replacing fossil-fuel-based electricity with the high penetration of affordable solar PV electricity.The reduction of energy surplus realized by distributed energy production and P2P energy trading,within the smart grid results in less transmission loss and lower requirements for costly upgrading of existing grids.By adopting energy blockchain and smart contract technologies,energy secure trading with a low risk of privacy leakage could be accommodated.The prototype is examined through a case study,and the feasibility and efficiency of the proposed mechanism are further validated by scenario analysis.
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.
基金Supported by Theodor Bilharz Research Institute(Grant# 74D) in collaboration with the American University of Cairo
文摘AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.
文摘The present paper is basically written as a non-apologetic strong defence of the thesis that computation is part and parcel of a physical theory and by no means a mere numerical evaluation of the prediction of a theory which comes towards the end. Various general considerations as well as specific examples are given to illustrate and support our arguments. These examples range from the practical aspect to almost esoteric considerations but at the end, everything converges towards a unity of theory and computation presented in the form of modern fractal logic and transfinite quantum field theory in a Cantorian spacetime. It is true that all our examples are taken from physics but our discussion is applicable in equal measure to a much wider aspect of life.
文摘Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm﹣1. The band due to C-H band and called hydrocarbon band was found only in paralytic and Alzheimer diseased along with normal healthy controls. Carbide band (C=C) is found only in Duchenne muscular dystrophy, paralytic and Alzheimer’s disease patients. Amide I was intact in all disorders with normal persons. Peroxide band (O-O) was found in all the cases of study. Amide IV band was found in paralytic, muscular dystrophy, Alzheimer’s diseases and normal controls. The amide V band was found in Alzheimer’s diseases only. The appearance or disappearance of the bands is a good sign to understand the mechanisms at the molecular level. FTIR spectroscopy may help in the diagnosis of the disease at the early stage of the onset. This spectroscopy can be used nicely for the study of hair, vaginal fluid, nails, urine, mucus, semen, synovial fluid, blood, hemoproteins, skin, and tears for human beings. We can also use it to understand the effect of adulteration on food and paint technology. FTIR is an indicator to explore the changes occurring at molecular level.
