The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was foun...The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.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
Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the pre...Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.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
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 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
Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 c...Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects.The patients were divided into two groups according to the urinary albumin excretion rate(UAER),with 53 cases in the type 2 diabetes group(UAER<30μg/min)and 43 cases in the early diabetic nephropathy group(30μg/min≤UAER<300μg/min).PBG,FINS,and HbA1c levels were detected in 87 healthy patients.Results:The levels of PBG,FINS,and HbA1c in the early diabetic nephropathy group were higher than those in the control group(P<0.01)and the type 2 diabetes group(P<0.01).Conclusion:PBG,FINS,and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes;thus,controlling the levels of PBG,FINS,and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.展开更多
While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a p...While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.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
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
Objective:To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy(DN).Methods:The clinical data and biochemical indexes of 100 diabetic patients admitted t...Objective:To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy(DN).Methods:The clinical data and biochemical indexes of 100 diabetic patients admitted to our hospital from October 2021 to October 2022 were retrospectively analyzed.The patients were divided into a DN group,which consisted of 55 cases,and a nondiabetic nephropathy group(NDN),which consisted of 45 cases.The urinary microalbumin to creatinine ratio,the clinical data(gender,age,duration of the disease,and BMI),and the biochemical indexes(triglycerides[TG],low-density lipoprotein cholesterol[LDL-C],high-density lipoprotein cholesterol[HDL-C],total cholesterol[TC],glycated hemoglobin A1c[HbA1c],systolic blood pressure[SBP],diastolic blood pressure[DBP])of the two groups were compared.Subsequently,the risk factors related to the progression of renal function deterioration in DN were analyzed through multifactorial logistic regression analysis.Results:No statistically significant difference was observed in the comparison of gender,age,BMI,LDL-C,and DBP between the two groups(P>0.05).The DN group demonstrated a longer disease duration and higher SBP,TC,HDL-C,HbA1c,and TG compared to the NDN group(P<0.05).Through multifactorial logistic regression analysis,it was found that the duration of the disease,the TC,the HDL-C,the HbA1c,the TG,and the SBP were independent risk factors of the deterioration of renal function in DN patients.Conclusion:Other than conventional indicators,TC,HDL-C,HbA1c,TG,and SBP are also crucial indicators in determining the progression of renal function deterioration in DN patients.展开更多
Objective:To explore the efficacy of auricular acupoint pressure patch combined with modified Huangqi Decoction in treating diabetic nephropathy.Methods:60 patients with diabetic nephropathy treated in our hospital fr...Objective:To explore the efficacy of auricular acupoint pressure patch combined with modified Huangqi Decoction in treating diabetic nephropathy.Methods:60 patients with diabetic nephropathy treated in our hospital from January 2021 to December 2022 were selected for this study.The patients were randomly divided into two groups using the random number table method,with 30 patients in each group.Among them,the control group was treated with conventional Western medicine,while the experimental group was treated with auricular acupoint pressure patches combined with modified Huangqi Decoction.The patients’fasting blood glucose(FPG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),urinary protein quantification,urea nitrogen(BUN),serum creatinine(SCr),and other indicators were detected and recorded before and after treatment.Results:Before treatment,there was no statistically significant difference in the FPG,the 2hPG,and the HbA1c between the two groups of patients(P>0.05);after treatment,the FPG,the 2hPG,and the HbA1c of the patients in the experimental group were significantly lower than those in the control group(P<0.05).Before treatment,there was no statistically significant difference in the urinary protein quantification,the BUN,and the SCr between the two groups of patients(P>0.05);after treatment,the urinary protein quantification,BUN,and SCr of the patients in the experimental group were significantly lower than those in the control group(P<0.05).The experimental group showed better improvement in symptoms such as fatigue,backache,and frequency of nocturia(P<0.05).Conclusion:Auricular acupoint pressure patch combined with modified Huangqi Decoction effectively treats diabetic nephropathy and it helps control blood sugar and renal function indicators and improve clinical symptoms,therefore improving the patients’quality of life.展开更多
Objectives: Diabetic nephropathy (DN) is one of the chronic microangiopathic complications of type 2 diabetes (T2DM) and has become the most frequent cause of end-stage renal disease. The XbaI polymorphism in the gluc...Objectives: Diabetic nephropathy (DN) is one of the chronic microangiopathic complications of type 2 diabetes (T2DM) and has become the most frequent cause of end-stage renal disease. The XbaI polymorphism in the glucose transporter (GLUT1) has been suggested in the development of DN. We examined the association between XbaI polymorphism of GLUT1 and susceptibility to T2DM and development of DN. Methods: The study included 227 T2DM patients divided into 107 without DN (DM ? DN) and 120 with DN (DM + DN), in addition to 100 apparently healthy controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The GLUT1 XbaI T allele was associated with increased susceptibility to T2DM, when comparing the healthy controls to the whole diabetic group, odds ratio (OR) = 1.899, 95% confidence interval (CI) (1.149 - 3.136), p = 0.011. This association was also significant between healthy controls and DM ? DN OR = 1.997 (1.079 - 3.699), p = 0.026 as well as between healthy controls and DM + DN OR = 1.818 (1.016 - 3.253), p = 0.042. However there was no significant association of XbaI polymorphism with DN when comparing DM ? DN to DM + DN OR = 0.910 (0.474 - 1.747), p = 0.777. Conclusion: XbaI T allele is associated with increased susceptibility to T2DM, but not to development of DN. Further studies are needed to replicate such findings.展开更多
The chronic complications of diabetes mellitus constitute a major public health problem.For example,diabetic eye diseases are the most important cause of blindness,and diabetic nephropathy is the most frequent cause o...The chronic complications of diabetes mellitus constitute a major public health problem.For example,diabetic eye diseases are the most important cause of blindness,and diabetic nephropathy is the most frequent cause of chronic kidney disease worldwide.The cellular and molecular mechanisms of these chronic complications are still poorly understood,preventing the development of effective treatment strategies.Tight junctions(TJs)are epithelial intercellular junctions located at the most apical region of cell-cell contacts,and their main function is to restrict the passage of molecules through the paracellular space.The TJs consist of over 40 proteins,and the most important are occludin,claudins and the zonula occludens.Accumulating evidence suggests that TJ disruption in different organs,such as the brain,nerves,retina and kidneys,plays a fundamental pathophysiological role in the development of chronic complications.Increased permeability of the blood-brain barrier and the blood-retinal barrier has been demonstrated in diabetic neuropathy,brain injury and diabetic retinopathy.The consequences of TJ disruption on kidney function or progression of kidney disease are currently unknown.In the present review,we highlighted the molecular events that lead to barrier dysfunction in diabetes.Further investigation of the mechanisms underlying TJ disruption is expected to provide new insights into therapeutic approaches to ameliorate the chronic complications of diabetes mellitus.展开更多
BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health b...BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.展开更多
Diabetic nephropathy is a major microvascular complication of diabetes,and it is one of the most common causes of the development of end-stage renal disease in patients with diabetes.MicroRNA is a kind of non-coding s...Diabetic nephropathy is a major microvascular complication of diabetes,and it is one of the most common causes of the development of end-stage renal disease in patients with diabetes.MicroRNA is a kind of non-coding single-stranded small molecule RNA,and miRNA-192 is highly expressed in the kidney and plays an important role in the development of diabetic nephropathy.This article reviews the pathogenesis of diabetic nephropathy,the mechanism of action of miRNA-192,and the treatment progress of diabetic nephropathy in order to provide new clues for the diagnosis and treatment of diabetic nephropathy.展开更多
Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin...Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.展开更多
Background:The increasing occurrence of diabetes mellitus(DM)noted worldwide has considerably elicited concern in the recent past.DM is associated with elevated vascular complications,morbidity,mortality,and poor qual...Background:The increasing occurrence of diabetes mellitus(DM)noted worldwide has considerably elicited concern in the recent past.DM is associated with elevated vascular complications,morbidity,mortality,and poor quality of life.In this context,mesenchymal stem cells(MSCs)have shown significant therapeutic potentialities in managing and curing type 1 DM owing to their self-renewable,immunosuppressive,and differentiation capacities.We investigated the potential action of N,N′-diphenyl-1,4-phenylenediamine(DPPD),a well-known synthetic antioxidant to enhance the therapeutic ability of the adipose-derived stem cells(AD-MSCs)in alleviating kidney and liver complications in diabetic rats.Methods:Over the four weeks of experiments,albino male rats(n=36)were split into six test groups:control,DPPD(250 mg/kg,i.p.),STZ-diabetic(D),D+DPPD,D+AD-MSCs(1×10^(6)cell/rat,i.v.),and D+AD-MSCs+DPPD treated groups.Results:Significant declines in the renal and hepatic oxidative stress markers(MDA,ROS,and AGEs)were observed coupled with a significant elevation in many antioxidant marker levels(GSH,SOD,CAT,GPx,HO-1,and TAC)in the diabetic rats treated with either DPPD or AD-MSCs or their co-administered injection compared to the diabetic untreated rats.This was suggested to be the leading cause of amelioration of the kidney functions(as measured by urea,uric acid,and creatine levels)and liver functions(as evidenced by the levels of AST,ALT,ALP,bilirubin,total proteins,albumin,and globulins).Conclusion:DPPD and AD-MSCs co-administration showed superior results in terms of the enhancement of the relative hepato-renal function,indicating the beneficial role of DPPD supplementation in increasing the therapeutic potential of AD-MSCs.展开更多
Background:Diabetic nephropathy(DN)is a serious complication of diabetes with rising prevalence worldwide.We aimed to explore the anti-DN mechanisms of the compound celastrol derived from the medicinal plant Tripteryg...Background:Diabetic nephropathy(DN)is a serious complication of diabetes with rising prevalence worldwide.We aimed to explore the anti-DN mechanisms of the compound celastrol derived from the medicinal plant Tripterygium wilfordii.Methods:Celastrol-related targets were obtained from Herbal Ingredients’Targets(HIT)and GeneCards databases.DN-related targets were retrieved from GeneCards,DisGeNET,and Therapeutic Targets Database(TTD).A Protein-protein interaction(PPI)network was established using the Search Tool for the Retrieval of Interacting Genes(STRING)database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using ClusterProfiler.The cytoHubba plugin was used to select the top 10 hub targets.Molecular docking was performed employing PyMOL and AutoDock software.Cell counting kit-8(CCK-8)and flow cytometry assays were used to detect the viability and apoptosis of NRK-52E cells,respectively.The mRNA expression levels of mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),and AKT serine/threonine kinase 1(AKT1)in NRK-52E cells were assessed using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We obtained sixty-six overlapping targets of celastrol and DN.GO and KEGG analyses demonstrated that the core targets of celastrol and DN were mainly involved in the inflammatory and immune response,oxidative stress,advanced glycation end products(AGEs)and their receptors(RAGEs)(AGE-RAGE),TNF,interleukin 17(IL-17),and MAPK signaling pathways.Finally,based on the good binding activity with celastrol,MAPK3,TNF,and AKT1 were identified as the foremost targets of celastrol.We observed that celastrol enhanced the viability of high glucose(HG)-treated NRK-52E cells and inhibited apoptosis in the in vitro assays.Moreover,celastrol decreased the mRNA expression levels of MAPK3,TNF,and AKT1 in high glucose(HG)-treated NRK-52E cells.Conclusion:Celastrol may treat DN by targeting APK3,TNF,and AKT1 and regulating inflammatory responses and oxidative stress through the AGE-RAGE,TNF,IL-17,and MAPK signaling pathways.展开更多
Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of D...Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.展开更多
文摘The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.
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.
基金supported by the Open Fund of State Key Laboratory of Tea Plant Biology and Utilization (SKLTOF20200127 and SKLT0F20200108)the Open Fund of Key Laboratory of Tea Plant Resources Comprehensive Development in South Henan Province (HNKLTOF2020005)the Zhejiang Provincial Basic Public Welfare Research Program Project (LGF20H280007)。
文摘Our previous study found that large-leaf yellow tea(LYT)had interesting hypoglycemic activity in high-fat diet-induced obese mice and highly safety in healthy mice. To study the anti-diabetic potential of LYT, the present study further investigated the preventive effects and mechanisms of action of LYT administration on diabetes and diabetic nephropathy in high-fat diet plus streptozotocin-induced diabetic mice. Results showed that LYT infusions(1/100 and 1/50, m/V)as drinking fluid for 4 weeks reduced diabetic polydipsia and polyuria, enhanced glucose tolerance and insulin sensitivity, and lowered fasting blood glucose level. The underlying mechanisms involve downregulation of gluconeogenesis(lower protein levels of TXNIP and FBP and enzyme activity of FBP), upregulation of lipid catabolism(higher protein levels of CPT-1α and PPARα), downregulation of lipogenesis(lower protein level of SREBP-1), and modification of the structure and abundance of gut microbiota to modulate metabolic homeostasis. Moreover, LYT administration prevented diabetic nephropathy, possibly due to reduced glucose-caused osmotic diuresis and lowered levels of renal PKC-β2, NLRP3 as well as membrane PKC-α, AQP2 and glycosylated AQP2 proteins. Taken together, LYT exhibits the activities in alleviating diabetic symptoms, ameliorating glucose and lipid dysmetabolism and fatty liver, and preventing diabetic nephropathy in diabetic mice. These activities may be explored for the prevention and treatment of diabetes in humans.
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.
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 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.
文摘Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects.The patients were divided into two groups according to the urinary albumin excretion rate(UAER),with 53 cases in the type 2 diabetes group(UAER<30μg/min)and 43 cases in the early diabetic nephropathy group(30μg/min≤UAER<300μg/min).PBG,FINS,and HbA1c levels were detected in 87 healthy patients.Results:The levels of PBG,FINS,and HbA1c in the early diabetic nephropathy group were higher than those in the control group(P<0.01)and the type 2 diabetes group(P<0.01).Conclusion:PBG,FINS,and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes;thus,controlling the levels of PBG,FINS,and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.
文摘While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.
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 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.
文摘Objective:To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy(DN).Methods:The clinical data and biochemical indexes of 100 diabetic patients admitted to our hospital from October 2021 to October 2022 were retrospectively analyzed.The patients were divided into a DN group,which consisted of 55 cases,and a nondiabetic nephropathy group(NDN),which consisted of 45 cases.The urinary microalbumin to creatinine ratio,the clinical data(gender,age,duration of the disease,and BMI),and the biochemical indexes(triglycerides[TG],low-density lipoprotein cholesterol[LDL-C],high-density lipoprotein cholesterol[HDL-C],total cholesterol[TC],glycated hemoglobin A1c[HbA1c],systolic blood pressure[SBP],diastolic blood pressure[DBP])of the two groups were compared.Subsequently,the risk factors related to the progression of renal function deterioration in DN were analyzed through multifactorial logistic regression analysis.Results:No statistically significant difference was observed in the comparison of gender,age,BMI,LDL-C,and DBP between the two groups(P>0.05).The DN group demonstrated a longer disease duration and higher SBP,TC,HDL-C,HbA1c,and TG compared to the NDN group(P<0.05).Through multifactorial logistic regression analysis,it was found that the duration of the disease,the TC,the HDL-C,the HbA1c,the TG,and the SBP were independent risk factors of the deterioration of renal function in DN patients.Conclusion:Other than conventional indicators,TC,HDL-C,HbA1c,TG,and SBP are also crucial indicators in determining the progression of renal function deterioration in DN patients.
文摘Objective:To explore the efficacy of auricular acupoint pressure patch combined with modified Huangqi Decoction in treating diabetic nephropathy.Methods:60 patients with diabetic nephropathy treated in our hospital from January 2021 to December 2022 were selected for this study.The patients were randomly divided into two groups using the random number table method,with 30 patients in each group.Among them,the control group was treated with conventional Western medicine,while the experimental group was treated with auricular acupoint pressure patches combined with modified Huangqi Decoction.The patients’fasting blood glucose(FPG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),urinary protein quantification,urea nitrogen(BUN),serum creatinine(SCr),and other indicators were detected and recorded before and after treatment.Results:Before treatment,there was no statistically significant difference in the FPG,the 2hPG,and the HbA1c between the two groups of patients(P>0.05);after treatment,the FPG,the 2hPG,and the HbA1c of the patients in the experimental group were significantly lower than those in the control group(P<0.05).Before treatment,there was no statistically significant difference in the urinary protein quantification,the BUN,and the SCr between the two groups of patients(P>0.05);after treatment,the urinary protein quantification,BUN,and SCr of the patients in the experimental group were significantly lower than those in the control group(P<0.05).The experimental group showed better improvement in symptoms such as fatigue,backache,and frequency of nocturia(P<0.05).Conclusion:Auricular acupoint pressure patch combined with modified Huangqi Decoction effectively treats diabetic nephropathy and it helps control blood sugar and renal function indicators and improve clinical symptoms,therefore improving the patients’quality of life.
文摘Objectives: Diabetic nephropathy (DN) is one of the chronic microangiopathic complications of type 2 diabetes (T2DM) and has become the most frequent cause of end-stage renal disease. The XbaI polymorphism in the glucose transporter (GLUT1) has been suggested in the development of DN. We examined the association between XbaI polymorphism of GLUT1 and susceptibility to T2DM and development of DN. Methods: The study included 227 T2DM patients divided into 107 without DN (DM ? DN) and 120 with DN (DM + DN), in addition to 100 apparently healthy controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The GLUT1 XbaI T allele was associated with increased susceptibility to T2DM, when comparing the healthy controls to the whole diabetic group, odds ratio (OR) = 1.899, 95% confidence interval (CI) (1.149 - 3.136), p = 0.011. This association was also significant between healthy controls and DM ? DN OR = 1.997 (1.079 - 3.699), p = 0.026 as well as between healthy controls and DM + DN OR = 1.818 (1.016 - 3.253), p = 0.042. However there was no significant association of XbaI polymorphism with DN when comparing DM ? DN to DM + DN OR = 0.910 (0.474 - 1.747), p = 0.777. Conclusion: XbaI T allele is associated with increased susceptibility to T2DM, but not to development of DN. Further studies are needed to replicate such findings.
文摘The chronic complications of diabetes mellitus constitute a major public health problem.For example,diabetic eye diseases are the most important cause of blindness,and diabetic nephropathy is the most frequent cause of chronic kidney disease worldwide.The cellular and molecular mechanisms of these chronic complications are still poorly understood,preventing the development of effective treatment strategies.Tight junctions(TJs)are epithelial intercellular junctions located at the most apical region of cell-cell contacts,and their main function is to restrict the passage of molecules through the paracellular space.The TJs consist of over 40 proteins,and the most important are occludin,claudins and the zonula occludens.Accumulating evidence suggests that TJ disruption in different organs,such as the brain,nerves,retina and kidneys,plays a fundamental pathophysiological role in the development of chronic complications.Increased permeability of the blood-brain barrier and the blood-retinal barrier has been demonstrated in diabetic neuropathy,brain injury and diabetic retinopathy.The consequences of TJ disruption on kidney function or progression of kidney disease are currently unknown.In the present review,we highlighted the molecular events that lead to barrier dysfunction in diabetes.Further investigation of the mechanisms underlying TJ disruption is expected to provide new insights into therapeutic approaches to ameliorate the chronic complications of diabetes mellitus.
基金Supported by Ningxia Natural Science Foundation,No.2022AAC02039National Natural Science Foundation of China,No.81860894,82260879,81674096Ningxia Innovation Team of the Foundation and Clinical Researches of Diabetes and its Complications,No.NXKJT2019010.
文摘BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.
基金Shandong provincial traditional Chinese medicine technology development plan(No.2019-0043)。
文摘Diabetic nephropathy is a major microvascular complication of diabetes,and it is one of the most common causes of the development of end-stage renal disease in patients with diabetes.MicroRNA is a kind of non-coding single-stranded small molecule RNA,and miRNA-192 is highly expressed in the kidney and plays an important role in the development of diabetic nephropathy.This article reviews the pathogenesis of diabetic nephropathy,the mechanism of action of miRNA-192,and the treatment progress of diabetic nephropathy in order to provide new clues for the diagnosis and treatment of diabetic nephropathy.
基金supported by the Joe,Pentti,and Tor Borg Memorial Fund.
文摘Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.
基金the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research at King Faisal University,Saudi Arabia,for financial support under the annual funding track(Grant 3730).
文摘Background:The increasing occurrence of diabetes mellitus(DM)noted worldwide has considerably elicited concern in the recent past.DM is associated with elevated vascular complications,morbidity,mortality,and poor quality of life.In this context,mesenchymal stem cells(MSCs)have shown significant therapeutic potentialities in managing and curing type 1 DM owing to their self-renewable,immunosuppressive,and differentiation capacities.We investigated the potential action of N,N′-diphenyl-1,4-phenylenediamine(DPPD),a well-known synthetic antioxidant to enhance the therapeutic ability of the adipose-derived stem cells(AD-MSCs)in alleviating kidney and liver complications in diabetic rats.Methods:Over the four weeks of experiments,albino male rats(n=36)were split into six test groups:control,DPPD(250 mg/kg,i.p.),STZ-diabetic(D),D+DPPD,D+AD-MSCs(1×10^(6)cell/rat,i.v.),and D+AD-MSCs+DPPD treated groups.Results:Significant declines in the renal and hepatic oxidative stress markers(MDA,ROS,and AGEs)were observed coupled with a significant elevation in many antioxidant marker levels(GSH,SOD,CAT,GPx,HO-1,and TAC)in the diabetic rats treated with either DPPD or AD-MSCs or their co-administered injection compared to the diabetic untreated rats.This was suggested to be the leading cause of amelioration of the kidney functions(as measured by urea,uric acid,and creatine levels)and liver functions(as evidenced by the levels of AST,ALT,ALP,bilirubin,total proteins,albumin,and globulins).Conclusion:DPPD and AD-MSCs co-administration showed superior results in terms of the enhancement of the relative hepato-renal function,indicating the beneficial role of DPPD supplementation in increasing the therapeutic potential of AD-MSCs.
基金supported by the Zhejiang Province Chinese Medicine Modernization Program Grant[Number 2020ZX001]the“Pioneer”and“Leading Goose”R&D Program of Zhejiang Grant[Number 2023C03075].
文摘Background:Diabetic nephropathy(DN)is a serious complication of diabetes with rising prevalence worldwide.We aimed to explore the anti-DN mechanisms of the compound celastrol derived from the medicinal plant Tripterygium wilfordii.Methods:Celastrol-related targets were obtained from Herbal Ingredients’Targets(HIT)and GeneCards databases.DN-related targets were retrieved from GeneCards,DisGeNET,and Therapeutic Targets Database(TTD).A Protein-protein interaction(PPI)network was established using the Search Tool for the Retrieval of Interacting Genes(STRING)database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using ClusterProfiler.The cytoHubba plugin was used to select the top 10 hub targets.Molecular docking was performed employing PyMOL and AutoDock software.Cell counting kit-8(CCK-8)and flow cytometry assays were used to detect the viability and apoptosis of NRK-52E cells,respectively.The mRNA expression levels of mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),and AKT serine/threonine kinase 1(AKT1)in NRK-52E cells were assessed using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We obtained sixty-six overlapping targets of celastrol and DN.GO and KEGG analyses demonstrated that the core targets of celastrol and DN were mainly involved in the inflammatory and immune response,oxidative stress,advanced glycation end products(AGEs)and their receptors(RAGEs)(AGE-RAGE),TNF,interleukin 17(IL-17),and MAPK signaling pathways.Finally,based on the good binding activity with celastrol,MAPK3,TNF,and AKT1 were identified as the foremost targets of celastrol.We observed that celastrol enhanced the viability of high glucose(HG)-treated NRK-52E cells and inhibited apoptosis in the in vitro assays.Moreover,celastrol decreased the mRNA expression levels of MAPK3,TNF,and AKT1 in high glucose(HG)-treated NRK-52E cells.Conclusion:Celastrol may treat DN by targeting APK3,TNF,and AKT1 and regulating inflammatory responses and oxidative stress through the AGE-RAGE,TNF,IL-17,and MAPK signaling pathways.
基金the National Natural Science Foundation of China(Grant Number:81970631 to W.L.).
文摘Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.
