Association between high-sensitivity troponin T levels below the ninety-ninth percentile and diabetic kidney disease: A crosssectional study

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.

The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes

Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including dementia.It is imperative to further understand the relation-ship between obesity,T2D,and cognitive deficits.Methods:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)mice.The CC mice are a genetically diverse panel derived from eight inbred strains.Results:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/6J.CC037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on sex.Glucose tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on HFD.Organ weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to HFD.Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.Conclusions:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and T2D.The genetic components may offer new tools for early prediction and prevention.

Recent progress in the genetics of diabetic microvascular complications

Diabetic complications including diabetic nephropathy,retinopathy,and neuropathy are as major causes of morbidity and mortality in diabetes individuals worldwide and current therapies are still unsatisfactory.One of the reasons for failure to develop effective treatment is the lack of fundamental understanding for underlying mechanisms.Genetic studies are powerful tools to dissect disease mechanism.The heritability(h2) was estimated to be 0.3-0.44 for diabetic nephropathy and 0.25-0.50 for diabetic retinopathy respectively.Previous linkage studies for diabetic nephropathy have identified overlapped linkage regions in 1q43-44,3q21-23,3q26,10p12-15,18q22-23,19q13,22q11-12.3 in multiple ethnic groups.Genome-wide association studies(GWAS) of diabetic nephropathy have been conducted in several populations.However,most of the identified risk loci could not be replicated by independent studies with a few exceptions including those in ELMO1,FRMD3,CARS,MYO16/IRS2,and APOL3-MYH9 genes.Functional studies of these genes revealed the involvement of cytoskeleton reorganization(especially non-muscle type myosin),phagocytosis of apoptotic cells,fibroblast migration,insulin signaling,and epithelial clonal expansion in the pathogenesis of diabetic nephropathy.Linkage analyses of diabetic retinopathy overlapped only in 1q36 region and current results from GWAS for diabetic retinopathy are inconsistent.Conclusive results from genetic studies for diabetic neuropathy are lacking.For now,small sample sizes,confounding by population stratification,different phenotype definitions between studies,ethnic-specific associations,the influence of environmental factors,and the possible contribution of rare variants may explain the inconsistencies between studies.

Non-Diabetic Nephropathies among Diabetic Patients of the Nephrology Department of Dakar

Introduction: Diabetic nephropathy is the most common cause of kidney disease in diabetics. However, in some cases the clinical symptoms is not typical and nephropathy may be different from diabetic and require the use of renal biopsy (RB) which is not usually indicated unless non-diabetic nephropathy (NND) is suspected. The objective of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) among the diabetic patients and to analyse the different predictive factors of its occurrence. Patients and methods: It was a retrospective, descriptive and analytical study which is carried out at the nephrology department of Aristide Le DANTEC hospital of Dakar over a period of 60 months. Diabetics with suspected NDN diagnosis based on renal anomalie that is associated with a recent diabetes, Acute renal failure with rapid progress, Diabetic retinopathy’s absence, and Extrarenal signs (cutaneous, digestive and articular) associated with an acute renal failure. Microscopic haematuria was included. The epidemiological, clinical, biological and histological parameters were collected and analysed using the SPSS, 3.5 version software. Results: Out of 34 biopsied diabetic patients, 12 had NDN that is a prevalence of 35, 3%. The average age was 49.88 ± 4.15 years, 0.78 for the sex-ratio and the mean duration of diabetes is 12.53 ± 4.7 years. Glomerular syndrome was found in 30 patients (88.23%), vascular nephropathy syndrome in 3 patients (8.82%) and tubule-interstitial nephropathy syndrome in only one patient (2.94%). Diabetic retinopathy (DR) and microscopic haematuria (HU) respectively existed in 10 patients (34%) and 15 patients (44. 12%). The Kidney biopsy (KB) indications were renal abnormalities associated with recent diabetes, acute renal failure with rapid progress, absence of DR, extrarenal signs associated with acute renal failure and microscopic haematuria. Twenty-two patients (64.7%) had diabetic nephropathy (DN) and 12 patients (38.2%) presented a NDN. Predictive factors of NDN diagnosis were a shorter diabetes duration (P = 0.0008), high blood pressure (P = 0.0015) and absence of DR (P = 0.005). Conclusion: Our data show that kidney injury in a diabetic is not always diabetic nephropathy. The Kidney biopsy (KB) is often needed in order to adopt an effective management.

Progress and challenges in genome-wide studies to understand the genetics of diabetic retinopathy

There are many advantages to understanding the genetics of human disease.Genetic markers can be used to calculate the risk of developing a disease,and elucidation of genetic risk factors can pinpoint the molecular aetiology of disease,which can facilitate the development of targeted therapies.Diabetic retinopathy(DR)is a common complication of diabetes that has a significant impact on quality of life.It has a clear genetic component,but determination of the genetic risk factors has proven difficult.To date,genome-wide studies for DR have been conducted on relatively small patient cohorts compared to other complex eye diseases and replication of genetic findings has been limited.The disease is highly heterogeneous,confounding attempts to classify patients into appropriate groups for genetic analysis and making direct comparisons between studies challenging.Future studies to determine the genetic causes of DR will need to focus on larger sample sizes,detailed phenotyping and appropriate classification of patients.Global co-operation and meta-analyses combining data from multiple studies will be critical to the discovery of genetic risk loci for DR.

The role of innate immunity in diabetic nephropathy and their therapeutic consequences

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.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

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.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

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.

Association of genetic variants with diabetic nephropathy

Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

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.

Genetics of type 2 diabetes

Type 2 diabetes(T2D) is the result of interaction between environmental factors and a strong hereditary component.We review the heritability of T2D as well as the history of genetic and genomic research in this area.Very few T2D risk genes were identified using candidate gene and linkage-based studies,but the advent of genome-wide association studies has led to the identification of multiple genes,including several that were not previously known to play any role in T2D.Highly replicated genes,for example TCF7L2,KCNQ1 and KCNJ11,are discussed in greater detail.Taken together,the genetic loci discovered to date explain only a small proportion of the observed heritability.We discuss possible explanations for this "missing heritability",including the role of rare variants,gene-environment interactions and epigenetics.The clinical utility of current findings and avenues of future research are also discussed.

Risk evaluation for diabetic retinopathy in Chinese renalbiopsied type 2 diabetes mellitus patients

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.

Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway

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.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

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.

Genetics of macrovascular complications in type 2 diabetes

Type 2 diabetes mellitus(T2DM)is a metabolic disorder that currently affects more than 400 million worldwide and is projected to cause 552 million cases by the year 2030.Long-term vascular complications,such as coronary artery disease,myocardial infarction,stroke,are the leading causes of morbidity and mortality among diabetic patients.The recent advances in genome-wide technologies have given a powerful impetus to the study of risk markers for multifactorial diseases.To date,the role of genetic and epigenetic factors in modulating susceptibility to T2DM and its vascular complications is being successfully studied that provides the accumulation of genomic knowledge.In the future,this will provide an opportunity to reveal the pathogenetic pathways in the development of the disease and allow to predict the macrovascular complications in T2DM patients.This review is focused on the evidence of the role of genetic variants and epigenetic changes in the development of macrovascular pathology in diabetic patients.

Recent advances in the molecular genetics of type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM) is a complex disease in which both genetic and environmental factors interact in determining impaired β-cell insulin secretion and peripheral insulin resistance. Insulin resistance in muscle, liver and fat is a prominent feature of most patients with T2DM and obesity, resulting in a reduced response of these tissues to insulin. Considerable evidence has been accumulated to indicate that heredity is a major determinant of insulin resistance and T2DM. It is believed that, among individuals destined to develop T2DM, hyperinsulinemia is the mechanism by which the pancreatic β-cell initially compensates for deteriorating peripheral insulin sensitivity, thus ensuring normal glucose tolerance. Most of these people will develop T2DM when β-cells fail to compensate. Despite the progress achieved in this field in recent years, the genetic causes of insulin resistance and T2DM remain elusive.Candidate gene association, linkage and genome-wide association studies have highlighted the role of genetic factors in the development of T2DM. Using these strategies, a large number of variants have been identified in many of these genes, most of which may influence both hepatic and peripheral insulin resistance, adipogenesis and β-cell mass and function. Recently, a new gene has been identified by our research group, the HMGA1 gene, whose loss of function can greatly raise the risk of developing T2DM in humans and mice. Functional genetic variants of the HMGA1 gene have been associated with insulin resistance syndromes among white Europeans, Chinese individuals and Americans of Hispanic ancestry. These findings may represent new ways to improve or even prevent T2DM.

Tiliroside protects against diabetic nephropathy in streptozotocininduced diabetes rats by attenuating oxidative stress and inflammation

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.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

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.

Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

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.

Exploring the genetic basis of childhood monogenic diabetes

Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being.The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity.In rare instances,mutations leading to severe insulin resistance can also result in the development of diabetes.Individuals diagnosed with specific types of monogenic diabetes,which are commonly found,can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes.Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments.This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.