BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this th...BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this threshold represent a heterogeneous group with an inadequately characterized risk profile.AIM To investigate the association between hs-TnT levels below the 99th percentile and the presence of diabetic kidney disease(DKD)in patients with diabetes mellitus.METHODS This study analyzed data from the National Health and Nutrition Examination Survey obtained between 1999 and 2004,focusing on adults with type 2 diabetes mellitus.Serum hs-TnT concentrations were evaluated.DKD was defined as impaired glomerular filtration rate(<60 mL/minute/1.73 m^(2)),proteinuria(urinary albumin-to-creatinine ratio of≥30 mg/g),or both conditions in patients with diabetes mellitus.Weighted multivariable logistic regression analysis and restricted cubic spline analyses were employed to examine the independent association between hs-TnT and DKD,with the likelihood ratio test being used to evaluate nonlinearity.RESULTS The study included 2505 patients with a mean age of 55.02(standard error:0.72)years,of whom 44.87%were females.Among the participants,909(32.34%)were diagnosed with DKD.Multivariable logistic regression analysis indicated that,compared to the lowest tertile of hs-TnT(<5.93 ng/L),tertile 2(5.94-9.79 ng/L)had an odds ratio of 1.25(95%confidence interval:0.77-2.02,P=0.350),while tertile 3(9.80-21.88 ng/L)had an odds ratio of 2.07(95%confidence interval:1.13-3.80,P=0.022),with a significant trend(P for trend=0.022).Smoothed curve fitting demonstrated a linear association between hs-TnT levels and DKD in the overall population(P=0.061 for nonlinearity)and in male(P=0.136 for nonlinearity)and female(P=0.067 for nonlinearity)subgroups.Further stratification and sensitivity analyses yielded consistent conclusions.CONCLUSION Our study findings suggest that in individuals with type 2 diabetes,detectable hs-TnT levels below the 99th percentile are associated with DKD.展开更多
Objective:To evaluate the efficacy of the modified Gui Fu Ling Wu Decoction in treating diabetic nephropathy(DN)of the spleen-kidney Yang deficiency type.Methods:A total of 100 DN patients admitted to Changyi Traditio...Objective:To evaluate the efficacy of the modified Gui Fu Ling Wu Decoction in treating diabetic nephropathy(DN)of the spleen-kidney Yang deficiency type.Methods:A total of 100 DN patients admitted to Changyi Traditional Chinese Medicine Hospital between August 2023 and March 2024 were included in the study.Patients were randomly divided into a control group and a study group,each comprising 50 cases,using a computerized random number generator.The control group received kallikrein treatment,while the study group received a combination of kallikrein and the modified Gui Fu Ling Wu Decoction.Blood glucose control,renal function,and inflammatory markers were assessed before and after treatment in both groups.Results:Before treatment,there were no significant differences in blood glucose and renal function indicators between the two groups(P>0.05).After treatment,postprandial blood glucose,fasting blood glucose,24-hour urinary protein,urinary microalbumin,serum creatinine,serum C-reactive protein(CRP),and interleukin-6 levels significantly decreased in both groups,with the study group showing superior results compared to the control group(P<0.05).Conclusion:The combination of Gui Fu Ling Wu Decoction and kallikrein for treating spleen-kidney Yang deficiency type DN significantly improves blood glucose control,enhances renal function,and reduces inflammatory responses.展开更多
AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA scree...AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.展开更多
Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of prot...Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.展开更多
BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations...BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.展开更多
BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therap...BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.展开更多
BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importanc...BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.展开更多
BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-f...BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-fibrotic properties,suggesting potential therapeutic benefits for DN.This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)antioxidant pathway.METHODS The effects of AC on high glucose(HG)-induced proliferation,inflammation,oxidative stress,and fibrosis were evaluated in rat glomerular mesangial cells(HBZY-1)in vitro.A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury,inflammation,oxidative stress,and fibrosis.The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats,including reduced body weight,and elevated blood glucose,serum creatinine,blood urea nitrogen,and 24-h urine protein.Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin(IL)-6,IL-8,tumor necrosis factor-alpha,reactive oxygen species,and malondialdehyde levels while increasing superoxide dismutase activity.Additionally,AC suppressed the expression of fibrogenic markers such as collagen I,collagen IV,and fibronectin.AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase(Quinone)1 protein expression in renal tissues and HG-induced HBZY-1 cells.CONCLUSION AC improves DN by reducing inflammation,oxidative stress,and fibrosis through the activation of the NRF2/HO-1 signaling pathway.These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.展开更多
BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascu...BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.展开更多
Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin...Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.展开更多
Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)i...Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or viruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.展开更多
AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)inci...AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this population.METHODS:A total of 84 renal-biopsied T2DM patients were included.Fundus and imaging examinations were employed for DR diagnosis.Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups.Risk factors on DR development were analyzed with multiple logistic regression.RESULTS:DR prevalence was 50%in total.The incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR group.Systolic blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR group.Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively correlated.CONCLUSION:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.展开更多
AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 20...AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.展开更多
BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(...BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.展开更多
BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the ro...BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN.展开更多
BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become anoth...BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.展开更多
Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor dete...Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.展开更多
BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuance...BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria.AIM To investigate Tiliroside's(Til)protective effect against diabetic nephropathy(DN)in rats under diabetic conditions.METHODS Five groups of six rats each were included in this study:Rats treated with DMSO by intraperitoneal injection as controls,those treated with STZ by intraperitoneal injection,those treated with STZ+Til(25 mg/kg body weight[bwt])or Til(50 mg/kg bwt),and those treated with anti-diabetic medication glibenclamide(600μg/kg bwt).Biochemical markers,fasting blood glucose,food intake,kidney weight,antioxidant enzymes,inflammatory and fibrotic markers,and renal injury were monitored in different groups.Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers.RESULTS Til significantly reduced biochemical markers,fasting blood glucose,food intake,and kidney weight and elevated antioxidant enzymes in diabetic rats.It also mitigated inflammatory and fibrotic markers,lessened renal injury,and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis.CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment,highlighting its promise for future drug development.展开更多
Diabetes is one of the most catastrophic diseases ruling every corner of the world,and this has led to elevated incidents of end-stage kidney disease(ESKD).The standard treatment for ESKD is kidney transplantation/rep...Diabetes is one of the most catastrophic diseases ruling every corner of the world,and this has led to elevated incidents of end-stage kidney disease(ESKD).The standard treatment for ESKD is kidney transplantation/replacement,which is limited due to a deficiency of donors.Hence,dialysis has become the second-best option for treating patients with ESKD.Patients with ESKD with underlying diabetes have an additional risk of complications and infections over non-diabetic ESKD patients.Furthermore,these patients also experience variations in blood glucose levels and are more liable to develop malnutrition.This article elaborates on the different dialysis methods for ESKD patients.This editorial highlights the evidence-based studies that include randomized clinical trials,cohort studies,retrospective studies and case-control studies and suggests the most suitable type of dialysis under the following components.展开更多
Renal epithelial-to-mesenchymal transition(EMT)is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells,resulting in renal abnormalities,including fibrosis.EMT can c...Renal epithelial-to-mesenchymal transition(EMT)is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells,resulting in renal abnormalities,including fibrosis.EMT can cause diabetic neph-ropathy through triggering kidney fibrosis,inflammation,and functional impair-ment.The diverse molecular pathways that drive EMT-mediated renal fibrosis are not utterly known.Targeting key signaling pathways involved in EMT may help ameliorate diabetic nephropathy and improve renal function.In such settings,un-derstanding precisely the complicated signaling networks is critical for develo-ping customized therapies to intervene in EMT-mediated diabetic nephropathy.展开更多
基金This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Gannan Medical University(approval No.EFYJ20240113007).
文摘BACKGROUND Identification of myocardial injury has traditionally relied on high-sensitivity troponin T(hs-TnT)levels exceeding the 99th percentile threshold.However,patients with detectable hs-TnT levels below this threshold represent a heterogeneous group with an inadequately characterized risk profile.AIM To investigate the association between hs-TnT levels below the 99th percentile and the presence of diabetic kidney disease(DKD)in patients with diabetes mellitus.METHODS This study analyzed data from the National Health and Nutrition Examination Survey obtained between 1999 and 2004,focusing on adults with type 2 diabetes mellitus.Serum hs-TnT concentrations were evaluated.DKD was defined as impaired glomerular filtration rate(<60 mL/minute/1.73 m^(2)),proteinuria(urinary albumin-to-creatinine ratio of≥30 mg/g),or both conditions in patients with diabetes mellitus.Weighted multivariable logistic regression analysis and restricted cubic spline analyses were employed to examine the independent association between hs-TnT and DKD,with the likelihood ratio test being used to evaluate nonlinearity.RESULTS The study included 2505 patients with a mean age of 55.02(standard error:0.72)years,of whom 44.87%were females.Among the participants,909(32.34%)were diagnosed with DKD.Multivariable logistic regression analysis indicated that,compared to the lowest tertile of hs-TnT(<5.93 ng/L),tertile 2(5.94-9.79 ng/L)had an odds ratio of 1.25(95%confidence interval:0.77-2.02,P=0.350),while tertile 3(9.80-21.88 ng/L)had an odds ratio of 2.07(95%confidence interval:1.13-3.80,P=0.022),with a significant trend(P for trend=0.022).Smoothed curve fitting demonstrated a linear association between hs-TnT levels and DKD in the overall population(P=0.061 for nonlinearity)and in male(P=0.136 for nonlinearity)and female(P=0.067 for nonlinearity)subgroups.Further stratification and sensitivity analyses yielded consistent conclusions.CONCLUSION Our study findings suggest that in individuals with type 2 diabetes,detectable hs-TnT levels below the 99th percentile are associated with DKD.
基金Shandong Province Traditional Chinese Medicine Science and Technology Project(Project No.M-2023290)。
文摘Objective:To evaluate the efficacy of the modified Gui Fu Ling Wu Decoction in treating diabetic nephropathy(DN)of the spleen-kidney Yang deficiency type.Methods:A total of 100 DN patients admitted to Changyi Traditional Chinese Medicine Hospital between August 2023 and March 2024 were included in the study.Patients were randomly divided into a control group and a study group,each comprising 50 cases,using a computerized random number generator.The control group received kallikrein treatment,while the study group received a combination of kallikrein and the modified Gui Fu Ling Wu Decoction.Blood glucose control,renal function,and inflammatory markers were assessed before and after treatment in both groups.Results:Before treatment,there were no significant differences in blood glucose and renal function indicators between the two groups(P>0.05).After treatment,postprandial blood glucose,fasting blood glucose,24-hour urinary protein,urinary microalbumin,serum creatinine,serum C-reactive protein(CRP),and interleukin-6 levels significantly decreased in both groups,with the study group showing superior results compared to the control group(P<0.05).Conclusion:The combination of Gui Fu Ling Wu Decoction and kallikrein for treating spleen-kidney Yang deficiency type DN significantly improves blood glucose control,enhances renal function,and reduces inflammatory responses.
文摘AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.:82100801,81974096,81770711,81974097,and 81961138007).
文摘Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.
基金Supported by National Natural Science Foundation of China,No.82205025,No.82374355 and No.82174293Subject of Jiangsu Province Hospital of Chinese Medicine,No.Y21023Forth Batch of Construction Program for Inheritance Office of Jiangsu Province Famous TCM Experts,No.[2021]7.
文摘BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.
基金Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province,China,No.2023257.
文摘BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.
基金Supported by Key Research and Development Program of Shandong Province,No.2021CXGC011101Special Fund for Taishan Scholars Project,No.tsqn202211324+2 种基金National Natural Science Foundation of China,No.81900669Natural Science Foundation of Shandong Province,China,No.ZR2018PH007the Multidisciplinary Innovation Center for Nephrology of the Second Hospital of Shandong University.
文摘BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.
基金Supported by the General Project of Anhui Provincial Health and Construction Commission,No.AHWJ2022b056.
文摘BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-fibrotic properties,suggesting potential therapeutic benefits for DN.This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)antioxidant pathway.METHODS The effects of AC on high glucose(HG)-induced proliferation,inflammation,oxidative stress,and fibrosis were evaluated in rat glomerular mesangial cells(HBZY-1)in vitro.A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury,inflammation,oxidative stress,and fibrosis.The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats,including reduced body weight,and elevated blood glucose,serum creatinine,blood urea nitrogen,and 24-h urine protein.Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin(IL)-6,IL-8,tumor necrosis factor-alpha,reactive oxygen species,and malondialdehyde levels while increasing superoxide dismutase activity.Additionally,AC suppressed the expression of fibrogenic markers such as collagen I,collagen IV,and fibronectin.AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase(Quinone)1 protein expression in renal tissues and HG-induced HBZY-1 cells.CONCLUSION AC improves DN by reducing inflammation,oxidative stress,and fibrosis through the activation of the NRF2/HO-1 signaling pathway.These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.
基金The study was reviewed and approved by the First People’s Hospital of Wenling(Approval No.KY-2023-2034-01).
文摘BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.
文摘Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.
基金sponsored by the National Natural Science Foundation of China(Grant No.:32371185)the Shanghai Science and Technology Plan Project,China(Project No.:23010504200)+3 种基金the“Shuguang Program”(Program No.:20SG50)funded by Shanghai Education Development FoundationShanghai Municipale Education Commission,China,the Shanghai Talent Development Fund,China(Grant No.:2020125)the Key Lab of Exercise and Health Sciences of Ministry of Education(Shanghai University of Sport,China)(Grant No.:2022KF001)the Shanghai Key Lab of Human Performance(Shanghai University of Sport,China)(Grant No.:11DZ2261100).
文摘Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or viruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.
基金Supported by the National Natural Science Foundation of China(No.82000885)Natural Science Foundation of Shanghai(No.21ZR1439700).
文摘AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this population.METHODS:A total of 84 renal-biopsied T2DM patients were included.Fundus and imaging examinations were employed for DR diagnosis.Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups.Risk factors on DR development were analyzed with multiple logistic regression.RESULTS:DR prevalence was 50%in total.The incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR group.Systolic blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR group.Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively correlated.CONCLUSION:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.
文摘AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.
基金Supported by Shanghai Pudong New Area Leading Talents Training Program Project,No.PWR12020-02Shanghai Pudong New Area Excellent Young Medical Talents Training Program Project,No.PWRq2023-40Shanghai Pudong New Area Health and Family Planning Scientific Research Project,No.PW2022A-91.
文摘BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.
基金pported by the Natural Science Foundation of Inner Mongolia Autonomous Region,No.2022MS08057.
文摘BACKGROUND The intricate relationship between type 2 diabetes mellitus(T2DM)and diabetic nephropathy(DN)presents a challenge in understanding the significance of various biomarkers in diagnosis.AIM To elucidate the roles and diagnostic values ofα2-macroglobulin(α2-MG),podocalyxin(PCX),α-L-fucosidase(AFU),retinol-binding protein-4(RBP-4),and cystatin C(CysC)in DN.METHODS From December 2018 to December 2020,203 T2DM patients were enrolled in the study.Of these,115 were diagnosed with DN(115 patients),while the remaining 88 patients were classified as non-DN.The urinary levels ofα2-MG,PCX,and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility.RESULTS After adjustments for age and gender,significant positive correlations were observed between the biomarkers CysC,RBP-4,α2-MG/urinary creatinine(UCr),PCX/UCr,and AFU/UCr,and clinical indicators such as urinary albumin-to-creatinine ratio(UACR),serum creatinine,urea,24-h total urine protein,and neutrophil-to-lymphocyte ratio(NLR).Conversely,these biomarkers exhibited negative correlations with the estimated glomerular filtration rate(P<0.05).Receiver operating characteristic(ROC)curve analysis further demonstrated the diagnostic performance of these biomarkers,with UACR showcasing the highest area under the ROC curve(AUC^(ROC))at 0.97.CONCLUSION This study underscores the diagnostic significance ofα2-MG,PCX,and AFU in the development of DN.The biomarkers RBP-4,CysC,PCX,AFU,andα2-MG provide promising diagnostic insights,while UACR is the most potent diagnostic biomarker in assessing DN.
基金Supported by the Natural Science Funds for Young Scholar of Hebei,China,No.H2020206108the Subject of Health Commission of Hebei,China,No.20210151.
文摘BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy(DN).The regulatory relationship between long noncoding RNAs(lncRNAs)and podocyte apoptosis has recently become another research hot spot in the DN field.AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3(Pdia3)could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.METHODS Using normal glucose or high glucose(HG)-cultured podocytes,the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress(ERS)were explored.LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction.Relative cell viability was detected through the cell counting kit-8 colorimetric assay.The podocyte apoptosis rate in each group was measured through flow cytometry.The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay.Finally,western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes.Next,lncRNA Pdia3 was involved in HG-induced podocyte apoptosis.Furthermore,the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p.LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.CONCLUSION Taken together,this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p,which might provide a potential therapeutic target for DN.
基金Supported by the National Natural Science Foundation of China,No.82100883the Research Project of Educational Commission of Jilin Province of China,No.JJKH20231214KJ.
文摘Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
基金the Ethical Committee of Shanxi Bethune Hospital(Approval No.YXLL-2023-222).
文摘BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria.AIM To investigate Tiliroside's(Til)protective effect against diabetic nephropathy(DN)in rats under diabetic conditions.METHODS Five groups of six rats each were included in this study:Rats treated with DMSO by intraperitoneal injection as controls,those treated with STZ by intraperitoneal injection,those treated with STZ+Til(25 mg/kg body weight[bwt])or Til(50 mg/kg bwt),and those treated with anti-diabetic medication glibenclamide(600μg/kg bwt).Biochemical markers,fasting blood glucose,food intake,kidney weight,antioxidant enzymes,inflammatory and fibrotic markers,and renal injury were monitored in different groups.Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers.RESULTS Til significantly reduced biochemical markers,fasting blood glucose,food intake,and kidney weight and elevated antioxidant enzymes in diabetic rats.It also mitigated inflammatory and fibrotic markers,lessened renal injury,and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis.CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment,highlighting its promise for future drug development.
文摘Diabetes is one of the most catastrophic diseases ruling every corner of the world,and this has led to elevated incidents of end-stage kidney disease(ESKD).The standard treatment for ESKD is kidney transplantation/replacement,which is limited due to a deficiency of donors.Hence,dialysis has become the second-best option for treating patients with ESKD.Patients with ESKD with underlying diabetes have an additional risk of complications and infections over non-diabetic ESKD patients.Furthermore,these patients also experience variations in blood glucose levels and are more liable to develop malnutrition.This article elaborates on the different dialysis methods for ESKD patients.This editorial highlights the evidence-based studies that include randomized clinical trials,cohort studies,retrospective studies and case-control studies and suggests the most suitable type of dialysis under the following components.
文摘Renal epithelial-to-mesenchymal transition(EMT)is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells,resulting in renal abnormalities,including fibrosis.EMT can cause diabetic neph-ropathy through triggering kidney fibrosis,inflammation,and functional impair-ment.The diverse molecular pathways that drive EMT-mediated renal fibrosis are not utterly known.Targeting key signaling pathways involved in EMT may help ameliorate diabetic nephropathy and improve renal function.In such settings,un-derstanding precisely the complicated signaling networks is critical for develo-ping customized therapies to intervene in EMT-mediated diabetic nephropathy.
