Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in D...Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.展开更多
Objective:Type 2 diabetes mellitus(T2DM)is characterized by insufficient insulin secretion and insulin resistance.Gypenosides(GPs)are the major bioactive saponins extracted from Gynostemma pentaphyllum.Previous studie...Objective:Type 2 diabetes mellitus(T2DM)is characterized by insufficient insulin secretion and insulin resistance.Gypenosides(GPs)are the major bioactive saponins extracted from Gynostemma pentaphyllum.Previous studies suggest that GPs have beneficial effects on T2DM,but the underlying mechanisms remain unclear.This study aims to investigate whether GPs exert therapeutic effects by influencing RNA N^(6)-methyladenosine(m6A)methylation modification,thereby regulating the downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods:Expression levels and methylation changes of METTL3,METTL14,and FTO in T2DM were analyzed using public databases,and related pathways were explored via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The main active components of GPs were screened from pharmacological databases,followed by compound-target network construction,enrichment analyses,and prediction of potential targets and pathways.A T2DM model was induced in Sprague-Dawley rats using a high-fat/high-sugar diet combined with low-dose streptozotocin.Rats were randomly divided into 4 groups:GPs-treated group(GPG,400 mg/kg),positive control group(PCG,metformin 100 mg/kg),normal saline control group(CONTROL),and T2DM model group(MODEL).Fasting blood glucose(FBG),oral glucose tolerance test(OGTT)-area under the glucose curve from 0 to 120 min(AUC0-120),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),serum inflammatory factors,and tissue pathology of pancreas and liver hematoxylin and eosin(HE)staining were assessed.Real-time fluorescence quantitative PCR and Western blotting were used to detect RNA and protein expression levels of METTL3,METTL14,FTO,PI3K,and AKT in pancreatic tissues.Molecular docking was applied to evaluate interactions between GPs’main components and METTL3,METTL14,and FTO to infer potential binding modes.Results:Bioinformatic analyses showed downregulation of METTL3/14 and upregulation of FTO in T2DM samples(all P<0.05),with enrichment in pathways related to insulin signaling,PI3K/AKT activation,oxidative stress response,and hormone secretion.Network pharmacology indicated that GPs components may act on targets involved in RNA modification and insulin-related pathways.In diabetic rats,GPs significantly reduced FBG,improved glucose tolerance,decreased HOMA-IR,and decreased the serum tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 levels compared with MODEL(all P<0.05).Pancreatic pathology showed alleviated islet injury and improved cell morphology.GPs treatment upregulated METTL3/14 mRNA and protein levels,and down-regulated FTO mRNA/protein levels in pancreatic tissue(all P<0.05).PI3K and AKT expression levels increased(both P<0.05),consistent with activation of downstream signals related to glucose uptake and improved insulin sensitivity.Metformin also improved metabolic indices but exhibited a different regulatory pattern on m6A-related enzymes compared with GPs.Molecular docking revealed stable interactions between core GPs saponin structures and methyltransferase-like 3(METTL3),methyltransferase-like 14(METTL14),or obesityassociated protein(FTO),suggesting that GPs may directly or indirectly modulate m6A regulatory proteins.Conclusion:GPs can effectively improve glucose-metabolism disorders,reduce inflammation,and protect pancreatic tissue in T2DM rats.The mechanisms may be associated with METTL3/14 up-regulation and FTO down-regulation,leading to enhanced m6A methylation and subsequent activation of the PI3K/AKT signaling pathway.These findings provide strong evidence for GPs regulation of epigenetic m6A RNA modification and insulin-related downstream pathways,and suggest that natural compounds targeting m6A regulation may be explored in the future for metabolic disease interventions.展开更多
OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,bl...OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,blood glucose levels,serum biochemical indexes,as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD)combined with six intraperitoneal injections of 35 mg·kg^(-1)of streptozotocin(STZ).The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C.In addition,NRK-C could also significantly improve glucose tolerance,hepatic glycogen levels,and lipid levels(total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein),and significantly reduced insulin resistance of diabetic mice,which played an important role in the antidiabetic effects.Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3βexpression was up-regulated after NRK-C intervention,indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.展开更多
BACKGROUND The volar approach with plate fixation is the gold standard for treating distal radius fractures,often requiring incision of the pronator quadratus(PQ)muscle.Preserving the PQ during surgery may facilitate ...BACKGROUND The volar approach with plate fixation is the gold standard for treating distal radius fractures,often requiring incision of the pronator quadratus(PQ)muscle.Preserving the PQ during surgery may facilitate early postoperative recovery.However,conventional minimally invasive plate osteosynthesis(MIPO)techniques frequently necessitate multiple(3-4)intraoperative fluoroscopic adjustments to achieve optimal plate positioning,which can inadvertently damage the PQ muscle.Based on our clinical observations,we developed a novel 3-point positioning technique to minimize PQ injury while ensuring accurate plate placement.Preliminary results demonstrate promising early clinical outcomes.AIM To retrospectively analyze distal radius fractures treated using the 3-point positioning-assisted MIPO technique with preservation of the PQ.METHODS The 3-point positioning technique was applied:The Kirschner wire was inserted after fluoroscopy and was correctly adjusted the position of the plate above the PQ.With the aid of Kirschner wires positioning the PQ stripping was performed only once,and the plate then placed in a correct and satisfactory position.Operation time,incision length,wrist pain score,upper extremity function disabilities of the arm,shoulder and hand(DASH)score,wrist Gartland-Werley score,wrist grip strength,and range of motion were among the quantitative variables recorded.Qualitative variables including AO fracture classification,intraoperative and postoperative complications were evaluated.RESULTS At a mean follow-up of 6.9±0.8 months,the mean scar length was 25.4±1.5 mm,the pain score was 0.7±0.6,the DASH score for the upper limb was 4.7±1.3,and the Gartland-Werley score for wrist function was 4.1±1.1 at the last follow-up.Mean flexion was 97.3%,extension was 97.0%,pronation was 98.9%,supination was 98.9%,and grip strength was 86.6%compared to contralateral values.No unfavorable intraoperative or postoperative complications occurred.CONCLUSION The 3-point positioning technique may reduce the damage to the PQ muscle and is a safe and effective method for MIPO for distal radius fractures.展开更多
This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasize...This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.展开更多
BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of mi...BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of microRNAs(e.g.,miR-495-3p),adiponectin(ADPN),and cardiometabolic index(CMI)in metabolic and renal pathologies.However,their combined predictive value for T2DN prognosis is not well understood.AIM To explore serum miR-495-3p,ADPN,and CMI levels in T2DN and their value in predicting prognosis.METHODS A total of 98 T2DN patients(study group)and 49 type 2 diabetic patients with normal renal function(control group)were enrolled from February 2020 to February 2022.Serum levels of miR-495-3p,ADPN,and CMI were measured in both groups.Patients were followed up for 6 months to assess prognosis.Dif-ferences between groups were analyzed,and multivariate logistic regression and receiver operating characteristic(ROC)curve analyses were performed to eva-luate the predictive value of these biomarkers.RESULTS The study group exhibited significantly lower miR-495-3p levels and higher ADPN and CMI levels compared to the control group(P<0.05).Poor prognosis patients had even lower miR-495-3p and higher ADPN and CMI levels than those with good prognosis(P<0.05).Multivariate analysis identified alanine amino-transferase,aspartate aminotransferase,urea nitrogen,serum creatinine,miR-495-3p,ADPN,and CMI as independent predictors of prognosis(P<0.05).ROC analysis revealed area under the curve values of 0.762(miR-495-3p),0.902(ADPN),0.757(CMI),0.899(alanine aminotransferase),0.852(aspartate ami-notransferase),0.916(urea nitrogen),and 0.910(serum creatinine)for predicting poor prognosis(P<0.05).CONCLUSION Low miR-495-3p and high ADPN and CMI levels are linked to T2DN and poor prognosis,highlighting their potential for risk prediction and clinical management.展开更多
This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitu...This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.展开更多
Objective:To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus(T2DM).Methods:A rat model of T2DM was established by a high-fat diet and streptozotoc...Objective:To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus(T2DM).Methods:A rat model of T2DM was established by a high-fat diet and streptozotocin administration.Rats were then treated with imrecoxib 10,20,or 40 mg/kg for 5 weeks.Body weight and fasting blood glucose levels were measured.The analysis included serum liver function,blood lipid profiles,and the levels of inflammatory factors in the rats.Liver tissue histology was evaluated using hematoxylin and eosin staining.Western blotting was conducted to measure the liver expression of proteins such as AKT,PI3K,NF-κB,p-AKT,p-PI3K,and p-NF-κB.Results:Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats.Compared to untreated diabetic rats,imrecoxib at all three doses reduced alanine aminotransferase,aspartate aminotransferase,triglycerides,cholesterol,tumor necrosis factor-α,interleukin(IL)-6,and IL-1β,and significantly increased the levels of IL-10 and IL-4.In imrecoxib-treated rats,the expression levels of AKT,PI3K,p-AKT,and p-PI3K were higher in comparison to the diabetes group,whereas the expression of p-NF-κB was lower.Conclusions:Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.展开更多
Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacill...Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82130101)the Youth Innovation Promotion Association of CAS(Grant No.2021333).
文摘Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.
基金supported by College Students’Innovative Entrepreneurial Training Plan Program of Guizhou Province,China(S202210660105,S202310660055)。
文摘Objective:Type 2 diabetes mellitus(T2DM)is characterized by insufficient insulin secretion and insulin resistance.Gypenosides(GPs)are the major bioactive saponins extracted from Gynostemma pentaphyllum.Previous studies suggest that GPs have beneficial effects on T2DM,but the underlying mechanisms remain unclear.This study aims to investigate whether GPs exert therapeutic effects by influencing RNA N^(6)-methyladenosine(m6A)methylation modification,thereby regulating the downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods:Expression levels and methylation changes of METTL3,METTL14,and FTO in T2DM were analyzed using public databases,and related pathways were explored via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The main active components of GPs were screened from pharmacological databases,followed by compound-target network construction,enrichment analyses,and prediction of potential targets and pathways.A T2DM model was induced in Sprague-Dawley rats using a high-fat/high-sugar diet combined with low-dose streptozotocin.Rats were randomly divided into 4 groups:GPs-treated group(GPG,400 mg/kg),positive control group(PCG,metformin 100 mg/kg),normal saline control group(CONTROL),and T2DM model group(MODEL).Fasting blood glucose(FBG),oral glucose tolerance test(OGTT)-area under the glucose curve from 0 to 120 min(AUC0-120),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),serum inflammatory factors,and tissue pathology of pancreas and liver hematoxylin and eosin(HE)staining were assessed.Real-time fluorescence quantitative PCR and Western blotting were used to detect RNA and protein expression levels of METTL3,METTL14,FTO,PI3K,and AKT in pancreatic tissues.Molecular docking was applied to evaluate interactions between GPs’main components and METTL3,METTL14,and FTO to infer potential binding modes.Results:Bioinformatic analyses showed downregulation of METTL3/14 and upregulation of FTO in T2DM samples(all P<0.05),with enrichment in pathways related to insulin signaling,PI3K/AKT activation,oxidative stress response,and hormone secretion.Network pharmacology indicated that GPs components may act on targets involved in RNA modification and insulin-related pathways.In diabetic rats,GPs significantly reduced FBG,improved glucose tolerance,decreased HOMA-IR,and decreased the serum tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 levels compared with MODEL(all P<0.05).Pancreatic pathology showed alleviated islet injury and improved cell morphology.GPs treatment upregulated METTL3/14 mRNA and protein levels,and down-regulated FTO mRNA/protein levels in pancreatic tissue(all P<0.05).PI3K and AKT expression levels increased(both P<0.05),consistent with activation of downstream signals related to glucose uptake and improved insulin sensitivity.Metformin also improved metabolic indices but exhibited a different regulatory pattern on m6A-related enzymes compared with GPs.Molecular docking revealed stable interactions between core GPs saponin structures and methyltransferase-like 3(METTL3),methyltransferase-like 14(METTL14),or obesityassociated protein(FTO),suggesting that GPs may directly or indirectly modulate m6A regulatory proteins.Conclusion:GPs can effectively improve glucose-metabolism disorders,reduce inflammation,and protect pancreatic tissue in T2DM rats.The mechanisms may be associated with METTL3/14 up-regulation and FTO down-regulation,leading to enhanced m6A methylation and subsequent activation of the PI3K/AKT signaling pathway.These findings provide strong evidence for GPs regulation of epigenetic m6A RNA modification and insulin-related downstream pathways,and suggest that natural compounds targeting m6A regulation may be explored in the future for metabolic disease interventions.
文摘OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,blood glucose levels,serum biochemical indexes,as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD)combined with six intraperitoneal injections of 35 mg·kg^(-1)of streptozotocin(STZ).The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C.In addition,NRK-C could also significantly improve glucose tolerance,hepatic glycogen levels,and lipid levels(total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein),and significantly reduced insulin resistance of diabetic mice,which played an important role in the antidiabetic effects.Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3βexpression was up-regulated after NRK-C intervention,indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.
基金Supported by Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopaedic Trauma,No.2020Y2014Fuzhou Health Technology Innovation Platform Construction Project,No.2019-S-wp2.
文摘BACKGROUND The volar approach with plate fixation is the gold standard for treating distal radius fractures,often requiring incision of the pronator quadratus(PQ)muscle.Preserving the PQ during surgery may facilitate early postoperative recovery.However,conventional minimally invasive plate osteosynthesis(MIPO)techniques frequently necessitate multiple(3-4)intraoperative fluoroscopic adjustments to achieve optimal plate positioning,which can inadvertently damage the PQ muscle.Based on our clinical observations,we developed a novel 3-point positioning technique to minimize PQ injury while ensuring accurate plate placement.Preliminary results demonstrate promising early clinical outcomes.AIM To retrospectively analyze distal radius fractures treated using the 3-point positioning-assisted MIPO technique with preservation of the PQ.METHODS The 3-point positioning technique was applied:The Kirschner wire was inserted after fluoroscopy and was correctly adjusted the position of the plate above the PQ.With the aid of Kirschner wires positioning the PQ stripping was performed only once,and the plate then placed in a correct and satisfactory position.Operation time,incision length,wrist pain score,upper extremity function disabilities of the arm,shoulder and hand(DASH)score,wrist Gartland-Werley score,wrist grip strength,and range of motion were among the quantitative variables recorded.Qualitative variables including AO fracture classification,intraoperative and postoperative complications were evaluated.RESULTS At a mean follow-up of 6.9±0.8 months,the mean scar length was 25.4±1.5 mm,the pain score was 0.7±0.6,the DASH score for the upper limb was 4.7±1.3,and the Gartland-Werley score for wrist function was 4.1±1.1 at the last follow-up.Mean flexion was 97.3%,extension was 97.0%,pronation was 98.9%,supination was 98.9%,and grip strength was 86.6%compared to contralateral values.No unfavorable intraoperative or postoperative complications occurred.CONCLUSION The 3-point positioning technique may reduce the damage to the PQ muscle and is a safe and effective method for MIPO for distal radius fractures.
文摘This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.
文摘BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of microRNAs(e.g.,miR-495-3p),adiponectin(ADPN),and cardiometabolic index(CMI)in metabolic and renal pathologies.However,their combined predictive value for T2DN prognosis is not well understood.AIM To explore serum miR-495-3p,ADPN,and CMI levels in T2DN and their value in predicting prognosis.METHODS A total of 98 T2DN patients(study group)and 49 type 2 diabetic patients with normal renal function(control group)were enrolled from February 2020 to February 2022.Serum levels of miR-495-3p,ADPN,and CMI were measured in both groups.Patients were followed up for 6 months to assess prognosis.Dif-ferences between groups were analyzed,and multivariate logistic regression and receiver operating characteristic(ROC)curve analyses were performed to eva-luate the predictive value of these biomarkers.RESULTS The study group exhibited significantly lower miR-495-3p levels and higher ADPN and CMI levels compared to the control group(P<0.05).Poor prognosis patients had even lower miR-495-3p and higher ADPN and CMI levels than those with good prognosis(P<0.05).Multivariate analysis identified alanine amino-transferase,aspartate aminotransferase,urea nitrogen,serum creatinine,miR-495-3p,ADPN,and CMI as independent predictors of prognosis(P<0.05).ROC analysis revealed area under the curve values of 0.762(miR-495-3p),0.902(ADPN),0.757(CMI),0.899(alanine aminotransferase),0.852(aspartate ami-notransferase),0.916(urea nitrogen),and 0.910(serum creatinine)for predicting poor prognosis(P<0.05).CONCLUSION Low miR-495-3p and high ADPN and CMI levels are linked to T2DN and poor prognosis,highlighting their potential for risk prediction and clinical management.
基金Supported by Fujian Provincial Science and Technology Innovation Joint Fund Project,No.2024Y9555Youth Research Project of the Science and Technology Plan of Fujian Provincial Health Commission,No.2024QNB005+1 种基金Fujian Provincial Natural Science Foundation Project,No.2024J011124Fujian Provincial Medical Project for Creating Dual High-Quality Development(High Level and High Standard),No.ETK2025004.
文摘This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.
基金funded by the“Hengrui-Tianqing Medical Education Fund”of the Second Affiliated Hospital of Wannan Medical College(grant no.HXKT2022026)Natural Science Research Program for Universities in Anhui Province(grant no.2023AH051739).
文摘Objective:To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus(T2DM).Methods:A rat model of T2DM was established by a high-fat diet and streptozotocin administration.Rats were then treated with imrecoxib 10,20,or 40 mg/kg for 5 weeks.Body weight and fasting blood glucose levels were measured.The analysis included serum liver function,blood lipid profiles,and the levels of inflammatory factors in the rats.Liver tissue histology was evaluated using hematoxylin and eosin staining.Western blotting was conducted to measure the liver expression of proteins such as AKT,PI3K,NF-κB,p-AKT,p-PI3K,and p-NF-κB.Results:Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats.Compared to untreated diabetic rats,imrecoxib at all three doses reduced alanine aminotransferase,aspartate aminotransferase,triglycerides,cholesterol,tumor necrosis factor-α,interleukin(IL)-6,and IL-1β,and significantly increased the levels of IL-10 and IL-4.In imrecoxib-treated rats,the expression levels of AKT,PI3K,p-AKT,and p-PI3K were higher in comparison to the diabetes group,whereas the expression of p-NF-κB was lower.Conclusions:Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.
基金supported by research grants from the Guangdong Province Basic and Applied Basic Research Fund Project(2022A1515110447)Open Fund Project of the State Key Laboratory of Applied Microbiology in South China(SKLAM006-2022)+1 种基金74th batch of general funding from the China Postdoctoral Science Foundation(2023M740774)Guangdong Provincial People’s Hospital,Postdoctoral Research Launch Fund(BY012022017)。
文摘Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.
