Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg...Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg-Glu-Lys-Ala)is a pentapeptide that specifically binds to fibronectin(FN),and the CREKA-modified liposome(CREKA-Lip)represents a novel FN-targeted drug delivery system.This study aimed to investigate the role of TP in diabetic db/db mice and determine whether encapsulation within CREKA-Lip enhances therapeutic efficacy while reducing the multi-organ toxicity of TP.Methods Eight-week-old diabetic db/db mice received tail vein injections twice weekly with vehicle,free TP,or CREKA-Lip/TP for 10 weeks.Urine and serum parameters were measured,and kidney,heart,liver,and testis tissues were collected for pathological evaluation.Protein-protein interaction networks were constructed using Cytoscape and its plug-ins to identify core targets and elucidate the therapeutic mechanism of TP against DN.Inflammatory,fibrotic,apoptotic,and lipid metabolism markers were evaluated in the kidneys of diabetic mice with DN and in high glucose-treated mouse mesangial cells and podocytes using qPCR,Western blot,immunohistochemistry,and immunofluorescence assays.Results TP administration reduced fasting blood glucose levels and glomerular mesangial expansion in diabetic mice.TP significantly suppressed renal inflammation,fibrosis,and apoptosis while enhancing lipid metabolism.Integration of network pharmacology,molecular docking,and transcriptomics revealed that TP ameliorated DN by inhibiting the JAK2-STAT1 signaling pathway.In vitro,TP inhibited high glucose-induced phosphorylation of JAK2 and STAT1,reduced collagen production in mesangial cells,decreased apoptosis,and improved lipid metabolism in podocytes.Moreover,CREKA-Lip/TP exhibited superior efficacy compared with free TP,with a more sustained reduction in urine albumin-to-creatinine ratio and greater inhibition of mesangial expansion.Notably,CREKA-Lip/TP treatment did not induce systemic toxicity.Conclusion TP improves renal inflammation,fibrosis,apoptosis,and lipid homeostasis,thereby ameliorating DN by inhibiting JAK2-STAT1 activation.Targeted delivery of TP via FN-binding CREKA-Lip enhances therapeutic efficacy while minimizing multi-organ toxicity.展开更多
BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies re...BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies reveal a high prevalence of BCN,little is known about this orphan acute kidney injury syndrome.AIM To address this knowledge gap,we performed a systematic review of case reports and case series of BCN,focusing on risk factors,diagnostic criteria,clinical presentation,kidney biopsy findings,severity,treatment approaches,and outcomes.METHODS Electronic databases were searched to identify eligible studies of patients with possible,probable,or definite BCN,using pre-established criteria.Relevant variables were extracted and analyzed.We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease.Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.RESULTS Sixty-seven case reports and six case series(involving 2 patients each)met the inclusion criteria,totaling 79 cases of BCN.The mean age was 48.3 years,and 83.5%were men.The most common cause of liver disease was drug-induced injury(30.4%),followed by infection(18.9%)and alcoholism(12.7%).BCN diagnosis was deemed definite,probable,and possible in 65.8%,32.9%,and 1.3%of cases,respectively.Levels of serum creatinine,dialysis requirement,and renal recovery did not differ among the total bilirubin tertile groups.However,both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group(P=0.011 and P=0.012,respectively).There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group(80%vs 52%,P=0.098).Finally,higher initial serum creatinine(per 1 mg/dL increase)was independently associated with dialysis requirement or death(adjusted odds ratio 1.291,95%confidence interval:1.032-1.615,P=0.025).CONCLUSION BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease.The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes.However,in alcoholic liver disease,BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease.Serum creatinine may be a valuable predictor of BCN prognosis.Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.展开更多
BACKGROUND Diabetic nephropathy(DN)is one of the most serious microvascular complications of type 2 diabetes mellitus(T2DM),and its incidence increases with the global rise in diabetes prevalence.It is the leading cau...BACKGROUND Diabetic nephropathy(DN)is one of the most serious microvascular complications of type 2 diabetes mellitus(T2DM),and its incidence increases with the global rise in diabetes prevalence.It is the leading cause of chronic kidney disease and end-stage kidney disease.Patients with DN often experience complex metabolic disorders and chronic inflammatory states,which not only accelerate the decline of renal function but are also closely related to complications such as cardiovascular events and osteoporosis(OP),seriously compromising quality of life.With the in-depth research on the gut microbiota and the emergence of concepts such as the"gut-kidney axis"and the"enteric-bone axis",the key roles of the gut microbiota and its metabolites in metabolic disorders,inflammatory responses,and target organ damage have been increasingly recognized.However,the specific role of gut microbiota in the pathogenesis of DN remains to be further explored.The results obtained may provide evidence to better understand the pathogenesis of DN and to identify high-risk populations at an early stage.This research direction is of strategic significance.AIM To assess the correlation of the gut microbiota metabolite trimethylamine N-oxide(TMAO)with inflammatory marker levels and OP in patients with DN.METHODS A total of 115 patients diagnosed with type 2 DN and treated at the Department of Endocrinology,Second Affiliated Hospital of Shandong First Medical University from August 2022 to December 2024 were enrolled in the DN group,and 115 patients with T2DM without nephropathy were included in the T2DM group.The two groups were compared in terms of gastrointestinal microbiota abundance and relative abundance at the genus level;levels of TMAO,inflammatory markers[including C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)],and bone metabolism markers[including procollagen type I N-terminal propeptide(PINP),β-CrossLaps(β-CTX),and alkaline phosphatase(ALP)];and lumbar spine and hip bone mineral density(BMD).The correlation of TMAO level with inflammatory factor and bone metabolism indicator levels was further analyzed.RESULTS The DN group had higher Chao1 and Simpson indices of gastrointestinal microbiota diversity than the T2DM group,whereas the ACE and Shannon indices were lower(P<0.05).The relative abundance of Firmicutes was higher,and the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria were lower in the DN group than in the T2DM group(P<0.05).CRP,IL-6,IL-8,TNF-α,and TMAO levels were considerably elevated in the DN group compared to the T2DM group(P<0.05).Moreover,the DN group had higher levels of bone turnover markers-including PINP,β-CTX,and ALP-but lower lumbar spine and hip BMDs than the T2DM group(P<0.05).TMAO level positively correlated with the Chao1 and Simpson indices and negatively correlated with the ACE and Shannon indices of gut microbiota diversity.TMAO level also negatively correlated with the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria and positively correlated with the abundance of Firmicutes.Additionally,TMAO level positively correlated with the inflammatory markers CRP,IL-6,IL-8,and TNF-α,as well as with the bone turnover markers PINP,β-CTX,and ALP.It negatively correlated with lumbar spine and hip BMDs(P<0.05).CONCLUSION Inflammatory and bone metabolic levels in patients with DN were found to be associated with the gut microbiota–derived metabolite TMAO.Elevated TMAO levels may mediate inflammatory responses and bone metabolism disorders in patients with DN,thereby contributing to the progression of systemic inflammation and OP.展开更多
BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effec...BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effective treatment options remain limited.AIM To evaluate the therapeutic impact of Shenzhuo formulation(SZF)on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.METHODS We established a DN mouse model through a high-fat diet combined with streptozotocin(STZ)injection,followed by SZF treatment.We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques.Additionally,based on transcriptomic and non-targeted metabolomic findings,we further assessed SZF’s influence on the expression of factors related to the cytochrome P450(CYP450)-mediated arachidonic acid(AA)metabolism pathway,as well as its effects on inflammation and oxidative stress.RESULTS SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice.Pathological analysis revealed that SZF treatment improved renal tissue damage,reduced fibrosis,and diminished glycogen deposition.Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes,including Cyp2j13,Cyp2b9,Pla2 g2e/Cyp4a12a,Cyp4a32,Cyp2e1,and Cyp4a14.Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway,including 5,6-EET,14,15-EET,phosphatidylcholine,and 20-HETE.Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue,as well as CYP2J and CYP2B proteins.Additionally,SZF significantly reduced the expression of inflammatory factors in renal tissue,enhanced antioxidant enzyme activity,and alleviated oxidative stress.CONCLUSION SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism,leading to improved renal function and improved pathological state in DN mice.展开更多
BACKGROUND The specific mechanism of diabetic nephropathy(DN)has not been fully elucidated,and more and more evidence shows that the development of DN is related to intestinal flora imbalance and micro-inflammatory st...BACKGROUND The specific mechanism of diabetic nephropathy(DN)has not been fully elucidated,and more and more evidence shows that the development of DN is related to intestinal flora imbalance and micro-inflammatory state process,and this mechanism urgently needs to be further clarified by relevant research.AIM To investigate the correlation between intestinal microbiota dysbiosis,low-grade inflammatory status,renal function impairment,and disease severity in older patients with DN,in order to provide a basis for the prevention and therapeutic intervention of DN.METHODS We enrolled 167 older patients with DN,diagnosed in the Department of Nephrology between June 2020 and June 2023.Eighty-five patients with type 2 diabetes mellitus(without DN)were enrolled to serve as the control group.A one-year follow-up observation was conducted.We compared the differences in gut microbiota composition,levels of inflammatory markers,and renal function indicators between the two groups,and the characteristics of gut microbiota and the changing patterns of inflammatory markers across different stages of disease progression.RESULTS In the DN group,the Chao,Ace,and Shannon indices were significantly lower,while the Simpson index was significantly higher than the control group.The relative abundances of Bacteroides and Bifidobacterium were significantly lower,whereas the relative abundances of Clostridium,Butyricimonas,Klebsiella,Enterococcus,Veillonella,and Megamonas were significantly higher than those in the control group(P<0.05).Estimated glomerular filtration rate was positively correlated with the Chao,Ace,and Shannon diversity indices of the gut microbiota,as well as with the relative abundances of Bacteroides,Bifidobacterium,and Akkermansia,and was negatively correlated with the relative abundances of Clostridium,Klebsiella,and Enterococcus(P<0.05).Logistic regression analysis indicated that lower Chao,Ace,and Shannon indices and higher Simpson index were associated with an increased risk of developing DN.After one year of follow-up,patients in the progression group exhibited a significantly greater decrease in Chao,Ace,and Shannon indices and a greater increase in Simpson index than the stable group.The reduction in the relative abundances of Bacteroides,Clostridium,Bifidobacterium,and Butyricimonas,as well as the increase in Klebsiella,Enterococcus,Veillonella,and Megamonas,were significantly more pronounced in the progression group than in the stable group(P<0.05).Regression analysis indicated that greater declines in Chao,Ace,and Shannon indices and Bacteroides relative abundance,along with greater increases in Simpson index and Enterococcus relative abundance,were associated with a more rapid decline in renal function.CONCLUSION The onset and progression of DN in older patients with diabetes are closely associated with gut microbiota composition.The more severe the dysbiosis,the lower the abundance of beneficial bacteria and the higher the abundance of harmful bacteria,leading to an increased risk of both DN occurrence and disease progression.展开更多
Diabetic nephropathy(DN)is one of the most serious complications of diabetes and a major cause of end-stage renal disease.However,due to the complexity of its pathogenesis,no new therapeutic drugs have been developed ...Diabetic nephropathy(DN)is one of the most serious complications of diabetes and a major cause of end-stage renal disease.However,due to the complexity of its pathogenesis,no new therapeutic drugs have been developed in the past 20 years,except for angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs).Breviscapine is a flavonoid active component isolated from Erigeron breviscapus,a member of the Asteraceae family.Pharmacological studies have confi rmed that this compound has antioxidant stress,anti-inflammatory regulation,anti-fibrosis and neuroprotective eff ects.Currently,it is mainly used in clinical practice as an adjuvant treatment for ischemic stroke and non-alcoholic fatty liver disease.Notably,although its antioxidant and anti-fibrotic properties have been verified in organs such as the liver and lungs,the mechanism of action in the field of DN has not been fully elucidated,especially the regulatory eff ect on the interstitial transformation of renal tubular epithelial cells remains to be revealed.Our research group has for the fi rst time systematically explored the molecular mechanism by which breviscapine improves high glucose-induced renal tubular fibrosis,providing a new theoretical basis for expanding its clinical application.展开更多
Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomeruloneph...Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.展开更多
Objective:To explore the key points of holistic nursing for children with membranous nephropathy(MN)combined with cerebral venous thrombosis,providing a reference for similar cases.Methods:The course of illness data o...Objective:To explore the key points of holistic nursing for children with membranous nephropathy(MN)combined with cerebral venous thrombosis,providing a reference for similar cases.Methods:The course of illness data of an 8-year-old boy with MN in the recurrent phase complicated with cerebral venous sinus thrombosis(CVST)was retroactively analyzed.Systematic nursing was implemented based on evidence-based practices,including strict neurological monitoring,anticoagulation and thrombolysis medication nursing,fluid and electrolyte management,hypoalbuminemia and edema nursing,complication prevention,and mental health education.Results:After 16 days of continuous infusion of low molecular weight heparin and supportive treatment,the child’s symptoms,such as headache and vomiting,disappeared.The reexamination of MRV showed significant absorption of thrombosis,and there was no residual neurological deficit.During the 3-month follow-up,the anticoagulation compliance was good,and there was no recurrence.Conclusion:Early identification of hypercoagulability risk,strengthening dynamic evaluation of neurological signs and coagulation indicators,standardizing anticoagulation and thrombolysis nursing,and cooperating with continuous health management can significantly improve the prognosis of children with MN combined with CVST.展开更多
Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-i...Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-induced rat model of membranous glomerulonephritis(MGN).Methods After model establishment,Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage.A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters.Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG,C3,and Sirt1.Western blotting was performed to measure the protein levels of podocin,nephrin,Sirt1,and factors involved in the NF-κB/p65 pathway.Inflammatory cytokine levels in renal homogenates were determined by ELISA.Results Safranal at 100 or 200 mg/kg reduced kidney weight(2.07±0.15 g and 2.05±0.15 g)and the kidney somatic index(0.83±0.08%and 0.81±0.08%)in MGN rats compared with those in the model group without drug administration(2.62±0.17 g and 1.05±0.1%).C-BSA increased the urine protein level to 117.68±10.52 mg/day(compared with the sham group,5.03±0.45 mg/day),caused dysregulation of renal function indicators,and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples.All the biochemical and histological changes were improved by safranal administration.Safranal at two doses also increased the fluorescence intensities of IgG(0.1±0.009 and 0.088±0.008)and C3(0.065±0.006 and 0.048±0.004)compared with those in the MGN group(0.15±0.013 and 0.086±0.008).Additionally,safranal reversed the downregulation of podocin,nephrin,and Wilms tumor protein-1(WT1)levels and reversed the high inflammatory cytokine levels in MGN rats.Mechanistically,safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.Conclusions Safranal ameliorates renal damage,inflammation,and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.展开更多
BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore ...BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.展开更多
Diabetic nephropathy(DN)is a well-known microvascular complication in patients with diabetes mellitus,which is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compart...Diabetic nephropathy(DN)is a well-known microvascular complication in patients with diabetes mellitus,which is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments,along with the hyalinization of intrarenal vasculature.DN has recently emerged as a leading cause of chronic and end-stage renal disease.While the pathobiology of other diabetic microvascular complications,such as retinopathy,is largely understood and has reasonable therapeutic options,the mechanisms and management strategies for DN remain incompletely elucidated.In this editorial,we comment on the article by Liu et al,focusing on the mechanisms underlying the detrimental impact ofβ-arrestin-2 on the kidneys in the context of DN.The authors suggest that inhibitingβ-arrestin-2 could alleviate renal damage through suppressing apoptosis of glomerular endothelial cells(GENCs),highlightingβ-arrestin-2 as a promising therapeutic target for DN.The study proposed thatβ-arrestin-2 triggers endoplasmic reticulum(ER)stress via the ATF6 signaling pathway,thereby promoting GENC apoptosis and exacerbating DN progression.Given the novel and crucial role ofβ-arrestin-2 in ER stress-related DN,it is imperative to further exploreβ-arrestin-2,its roles in ER stress and the potential therapeutic implications in DN.展开更多
Objective:To evaluate the efficacy and symptom scores of early diabetic nephropathy(DKD)treated with modified Shenqi Dihuang Decoction.Methods:82 patients with early DKD who visited the hospital from February 2023 to ...Objective:To evaluate the efficacy and symptom scores of early diabetic nephropathy(DKD)treated with modified Shenqi Dihuang Decoction.Methods:82 patients with early DKD who visited the hospital from February 2023 to February 2025 were randomly divided into two groups by drawing.Group A received modified Shenqi Dihuang Decoction+SGLT2 inhibitor,while Group B received SGLT2 inhibitor only.The efficacy,symptom scores,blood glucose,and renal function were compared between the two groups.Results:The efficacy of Group A was higher than that of Group B in the treatment of early DKD(P<0.05).The DKD symptom scores of Group A were lower than those of Group B(P<0.05).The fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG),and glycated hemoglobin(HbA1c)of Group A were better than those of Group B(P<0.05).The serum creatinine(SCr),blood urea nitrogen(BUN),and urinary albumin excretion rate(UAER)of Group A were also better than those of Group B.Conclusion:The combination of modified Shenqi Dihuang Decoction and SGLT2 inhibitor dapagliflozin has excellent efficacy in the treatment of early DKD,which can improve renal function,reduce DKD symptoms,and stabilize blood glucose levels.展开更多
Chinese herbal medicines(CHMs)and their bioactive compounds have demonstrated clinical effectiveness in treating and managing membranous nephropathy(MN),as evidenced by a comprehensive analysis of clinical trials,syst...Chinese herbal medicines(CHMs)and their bioactive compounds have demonstrated clinical effectiveness in treating and managing membranous nephropathy(MN),as evidenced by a comprehensive analysis of clinical trials,systematic reviews,and meta-analyses.The bioactive constituents of CHMs exert their therapeutic effects by modulating various signaling pathways,resulting in antioxidant,anti-inflammatory,and antifibrotic properties,as well as the regulation of autophagy.In contrast to conventional single-target approaches,traditional Chinese medicines formulas and phytochemicals employ a multi-target therapeutic strategy for MN,which has shown significant clinical efficacy and the potential to mitigate or reverse the damage.This evaluation provides a foundation for a comprehensive clinical understanding of the protective role of CHMs in the context of MN,highlighting their benefits and prospects in addressing this condition.展开更多
Background:Hypertensive nephropathy remains a leading cause of end-stage renal disease with limited targeted therapies.Methods:We conducted a bibliometric analysis(1992-2024)of 440 basic studies from 7 databases,using...Background:Hypertensive nephropathy remains a leading cause of end-stage renal disease with limited targeted therapies.Methods:We conducted a bibliometric analysis(1992-2024)of 440 basic studies from 7 databases,using VOSviewer and R to quantify research evolution.Intervention modalities,signaling pathways,and mechanisms were innovatively extracted.Results:Quantified analysis revealed a distinct temporal evolution:early research was dominated by TGF-βsignaling,while starting from 2015,the focus of the research turned to podocyte-targeted studies.Traditional Chinese medicine compounds emerged as the predominant intervention,yet standardization deficits persisted across 73 formulas.Despite limited human pathological concordance,Spontaneously hypertensive rats models were utilized in most studies.Critically,only a few podocyte-focused therapeutics advanced to clinical trials,primarily hindered by species-specific Transient receptor potential channel expression divergence and mesenchymal stem cells renal delivery.Conclusion:Podocyte protection and standardized traditional Chinese medicine are potential translational targets,but there is a lack of reliable clinical trials for clinical verification.展开更多
Objective:To evaluate the therapeutic effect of Shenqi Dihuang Decoction combined with calcium dobesilate on patients with diabetic nephropathy(DKD).Methods:90 patients with DKD who visited the hospital from March 202...Objective:To evaluate the therapeutic effect of Shenqi Dihuang Decoction combined with calcium dobesilate on patients with diabetic nephropathy(DKD).Methods:90 patients with DKD who visited the hospital from March 2024 to March 2025 were selected as samples and randomly divided into two groups.Group A was treated with Shenqi Dihuang Decoction combined with calcium dobesilate,while Group B was treated with calcium dobesilate alone.The efficacy,syndrome scores,blood glucose levels,and renal function indicators were compared between the two groups.Results:The efficacy of DKD treatment in Group A was higher than that in Group B(P<0.05).The syndrome scores in Group A were lower than those in Group B(P<0.05).The 2-hour postprandial blood glucose(PBG),fasting blood glucose(FBG),and glycated hemoglobin(HbA1c)levels in Group A were lower than those in Group B(P<0.05).The serum creatinine(SCr),urinary microalbumin,urinary albumin excretion rate(UAER),and β2-microglobulin(β2-MG)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:The treatment of DKD with Shenqi Dihuang Decoction combined with calcium dobesilate can stabilize blood glucose levels,improve renal function,and reduce syndrome scores,which is highly effective and feasible.展开更多
BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of mi...BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of microRNAs(e.g.,miR-495-3p),adiponectin(ADPN),and cardiometabolic index(CMI)in metabolic and renal pathologies.However,their combined predictive value for T2DN prognosis is not well understood.AIM To explore serum miR-495-3p,ADPN,and CMI levels in T2DN and their value in predicting prognosis.METHODS A total of 98 T2DN patients(study group)and 49 type 2 diabetic patients with normal renal function(control group)were enrolled from February 2020 to February 2022.Serum levels of miR-495-3p,ADPN,and CMI were measured in both groups.Patients were followed up for 6 months to assess prognosis.Dif-ferences between groups were analyzed,and multivariate logistic regression and receiver operating characteristic(ROC)curve analyses were performed to eva-luate the predictive value of these biomarkers.RESULTS The study group exhibited significantly lower miR-495-3p levels and higher ADPN and CMI levels compared to the control group(P<0.05).Poor prognosis patients had even lower miR-495-3p and higher ADPN and CMI levels than those with good prognosis(P<0.05).Multivariate analysis identified alanine amino-transferase,aspartate aminotransferase,urea nitrogen,serum creatinine,miR-495-3p,ADPN,and CMI as independent predictors of prognosis(P<0.05).ROC analysis revealed area under the curve values of 0.762(miR-495-3p),0.902(ADPN),0.757(CMI),0.899(alanine aminotransferase),0.852(aspartate ami-notransferase),0.916(urea nitrogen),and 0.910(serum creatinine)for predicting poor prognosis(P<0.05).CONCLUSION Low miR-495-3p and high ADPN and CMI levels are linked to T2DN and poor prognosis,highlighting their potential for risk prediction and clinical management.展开更多
Objective:To evaluate the efficacy of the modified Gui Fu Ling Wu Decoction in treating diabetic nephropathy(DN)of the spleen-kidney Yang deficiency type.Methods:A total of 100 DN patients admitted to Changyi Traditio...Objective:To evaluate the efficacy of the modified Gui Fu Ling Wu Decoction in treating diabetic nephropathy(DN)of the spleen-kidney Yang deficiency type.Methods:A total of 100 DN patients admitted to Changyi Traditional Chinese Medicine Hospital between August 2023 and March 2024 were included in the study.Patients were randomly divided into a control group and a study group,each comprising 50 cases,using a computerized random number generator.The control group received kallikrein treatment,while the study group received a combination of kallikrein and the modified Gui Fu Ling Wu Decoction.Blood glucose control,renal function,and inflammatory markers were assessed before and after treatment in both groups.Results:Before treatment,there were no significant differences in blood glucose and renal function indicators between the two groups(P>0.05).After treatment,postprandial blood glucose,fasting blood glucose,24-hour urinary protein,urinary microalbumin,serum creatinine,serum C-reactive protein(CRP),and interleukin-6 levels significantly decreased in both groups,with the study group showing superior results compared to the control group(P<0.05).Conclusion:The combination of Gui Fu Ling Wu Decoction and kallikrein for treating spleen-kidney Yang deficiency type DN significantly improves blood glucose control,enhances renal function,and reduces inflammatory responses.展开更多
Objective Forsythia suspensa has long been utilized in traditional Chinese medicine(TCM)for the treatment of IgA nephropathy(IgAN),the most prevalent form of primary glomerular disease.However,the precise mechanisms r...Objective Forsythia suspensa has long been utilized in traditional Chinese medicine(TCM)for the treatment of IgA nephropathy(IgAN),the most prevalent form of primary glomerular disease.However,the precise mechanisms remain inadequately understood.This study seeks to elucidate the underlying mechanisms of Forsythia suspensa extract(FSE)in the treatment of IgAN by employing an integrated approach that combines network pharmacology with in vivo experimental validation.Methods The chemical components of FSE were identified using high-performance liquid chromatography-mass spectrometry(HPLC–MS/MS).Additional chemical components and targets were determined through the Traditional Chinese Medicine Systems Pharmacology database.Potential therapeutic targets for IgAN were sourced from GeneCards and the Comparative Toxicogenomics Database.Subsequently,the enrichment analyses were conducted to evaluate the biological functions and pathways associated with the core targets.Finally,a mousemodel of IgAN was developed to validate the findings of the network pharmacology analysis.Results Through network analysis and HPLC–MS/MS,31 chemical components of FSE were identified.A total of 99 common targets were discovered between FSE and IgAN.The enrichment analyses suggested that FSE may mitigate IgAN primarily by inhibiting the TLR and NF-κB signaling pathways.In vivo experiments demonstrated that FSE reduced inflammation and preserved renal function in mice with IgAN through the Tolllike receptor 9(TLR9)/NF-κB pathway.Conclusion The integration of network pharmacology and animal experiments suggests that FSE alleviates renal inflammation and damage in IgAN through the TLR9/NF-κB signaling pathway.展开更多
Objective:To investigate the clinical efficacy of traditional Chinese medicine(TCM)syndrome differentiation in the treatment of patients with gouty nephropathy.Methods:From June 2023 to December 2024,80 patients with ...Objective:To investigate the clinical efficacy of traditional Chinese medicine(TCM)syndrome differentiation in the treatment of patients with gouty nephropathy.Methods:From June 2023 to December 2024,80 patients with gouty nephropathy were selected as samples and randomly divided into two groups:group A received TCM syndrome differentiation treatment,while group B received conventional treatment.The efficacy,laboratory indicators,symptom scores,and safety were compared between the two groups.Results:The efficacy of group A was higher than that of group B(P<0.05).The uric acid,blood urea nitrogen,serum creatinine,and 24-hour urinary protein levels in group A were lower than those in group B(P<0.05).The symptom score of group A was lower than that of group B(P<0.05).The adverse reactions of gouty nephropathy in group A were lower than those in group B(P<0.05).Conclusion:TCM syndrome differentiation treatment for gouty nephropathy can alleviate symptoms,protect renal function,and is highly effective and feasible.展开更多
Objective Th17 cell-mediated immune injury is a crucial factor contributing to tubulointerstitial fibrosis in patients with IgA nephropathy(IgAN).However,the exact mechanisms by which Th17 cells induce tubulointerstit...Objective Th17 cell-mediated immune injury is a crucial factor contributing to tubulointerstitial fibrosis in patients with IgA nephropathy(IgAN).However,the exact mechanisms by which Th17 cells induce tubulointerstitial fibrosis remain to be fully elucidated.Methods An IgAN mouse model was established and validated.Transcriptome sequencing,combined with bioinformatics analysis,was carried out to explore the immune injury pathways in renal tissues and the activation pathways in Th17 cells that were co-cultured with tubular epithelial cells.In subsequent experiments,small interfering RNA(siRNA)and overexpression plasmids were used to manipulate cellular targets.Validation was conducted through quantitative real-time polymerase chain reaction(qPCR),Western blotting,and immunofluorescence assays.Results Compared with the control mice,IgAN mice exhibited elevated serum creatinine levels and increased urine protein-to-creatinine ratios.Renal pathological examination revealed the characteristic features of IgAN.Transcriptomic analysis of the kidney tissues from the model mice showed the activation of Th17 differentiation pathways,which was further confirmed by immunofluorescence analysis showing increased expression of interleukin-17A(IL-17A).These findings indicate an increased abundance of Th17 cells with potential pathogenic significance.When Th17 cells were co-cultured with tubular epithelial cells,the level of interleukin-9(IL-9)in the system increased.This increase in IL-9 activated the Janus kinase 1-signal transducer and activator of transcription 3(JAK1-STAT3)pathway through the IL-9 receptor(IL-9R)and upregulated the signature transcription factor retinoic acid-related orphan receptor gamma(ROR-γ),thus promoting Th17 cell differentiation.When IL-9R was silenced using siRNA or when the activity of STAT3 was inhibited,both the levels of phosphorylated STAT3(p-STAT3)and ROR-γdecreased.Moreover,IL-17A secreted by Th17 cells promoted the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)in tubular epithelial cells by activating the IL-17 receptor A(IL-17RA)–adaptor protein Act1–tumor necrosis factor receptor-associated factor 6(TRAF6)complex.This process regulated the production of inflammatory cytokines and drove the initiation and progression of fibrosis.Treatment with a STAT3 inhibitor in IgAN mice led to a reduction in the number of renal Th17 cells and alleviated the fibrotic phenotype.Conclusion This study demonstrated that the interaction between Th17 cells and tubular epithelial cells triggers excessive extracellular matrix deposition in the tubulointerstitium,thereby exacerbating the fibrotic phenotype and accelerating the progression of IgAN.展开更多
文摘Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg-Glu-Lys-Ala)is a pentapeptide that specifically binds to fibronectin(FN),and the CREKA-modified liposome(CREKA-Lip)represents a novel FN-targeted drug delivery system.This study aimed to investigate the role of TP in diabetic db/db mice and determine whether encapsulation within CREKA-Lip enhances therapeutic efficacy while reducing the multi-organ toxicity of TP.Methods Eight-week-old diabetic db/db mice received tail vein injections twice weekly with vehicle,free TP,or CREKA-Lip/TP for 10 weeks.Urine and serum parameters were measured,and kidney,heart,liver,and testis tissues were collected for pathological evaluation.Protein-protein interaction networks were constructed using Cytoscape and its plug-ins to identify core targets and elucidate the therapeutic mechanism of TP against DN.Inflammatory,fibrotic,apoptotic,and lipid metabolism markers were evaluated in the kidneys of diabetic mice with DN and in high glucose-treated mouse mesangial cells and podocytes using qPCR,Western blot,immunohistochemistry,and immunofluorescence assays.Results TP administration reduced fasting blood glucose levels and glomerular mesangial expansion in diabetic mice.TP significantly suppressed renal inflammation,fibrosis,and apoptosis while enhancing lipid metabolism.Integration of network pharmacology,molecular docking,and transcriptomics revealed that TP ameliorated DN by inhibiting the JAK2-STAT1 signaling pathway.In vitro,TP inhibited high glucose-induced phosphorylation of JAK2 and STAT1,reduced collagen production in mesangial cells,decreased apoptosis,and improved lipid metabolism in podocytes.Moreover,CREKA-Lip/TP exhibited superior efficacy compared with free TP,with a more sustained reduction in urine albumin-to-creatinine ratio and greater inhibition of mesangial expansion.Notably,CREKA-Lip/TP treatment did not induce systemic toxicity.Conclusion TP improves renal inflammation,fibrosis,apoptosis,and lipid homeostasis,thereby ameliorating DN by inhibiting JAK2-STAT1 activation.Targeted delivery of TP via FN-binding CREKA-Lip enhances therapeutic efficacy while minimizing multi-organ toxicity.
文摘BACKGROUND Bile cast nephropathy(BCN)is suspected in the setting of liver disease and hyperbilirubinemia and is characterized by the formation of tubular bile casts and acute tubular injury.While postmortem studies reveal a high prevalence of BCN,little is known about this orphan acute kidney injury syndrome.AIM To address this knowledge gap,we performed a systematic review of case reports and case series of BCN,focusing on risk factors,diagnostic criteria,clinical presentation,kidney biopsy findings,severity,treatment approaches,and outcomes.METHODS Electronic databases were searched to identify eligible studies of patients with possible,probable,or definite BCN,using pre-established criteria.Relevant variables were extracted and analyzed.We explored the impact of serum total bilirubin levels and alcoholic liver disease on BCN severity and outcomes by stratifying cases into total bilirubin tertiles and alcoholic vs non-alcoholic liver disease.Univariate and multivariable logistic regression analyses were used to examine factors associated with the composite outcome of dialysis requirement or death.RESULTS Sixty-seven case reports and six case series(involving 2 patients each)met the inclusion criteria,totaling 79 cases of BCN.The mean age was 48.3 years,and 83.5%were men.The most common cause of liver disease was drug-induced injury(30.4%),followed by infection(18.9%)and alcoholism(12.7%).BCN diagnosis was deemed definite,probable,and possible in 65.8%,32.9%,and 1.3%of cases,respectively.Levels of serum creatinine,dialysis requirement,and renal recovery did not differ among the total bilirubin tertile groups.However,both initial and peak serum creatinine were significantly higher in the alcoholic liver disease group compared to the non-alcoholic group(P=0.011 and P=0.012,respectively).There was also a non-significant trend toward a higher incidence of dialysis requirement or death in the alcoholic liver disease group(80%vs 52%,P=0.098).Finally,higher initial serum creatinine(per 1 mg/dL increase)was independently associated with dialysis requirement or death(adjusted odds ratio 1.291,95%confidence interval:1.032-1.615,P=0.025).CONCLUSION BCN is a common and potentially serious cause of acute kidney injury in patients with liver disease.The degree of hyperbilirubinemia does not appear to correlate with BCN severity or outcomes.However,in alcoholic liver disease,BCN is associated with a greater rise in serum creatinine and a trend toward worse outcomes compared to non-alcoholic liver disease.Serum creatinine may be a valuable predictor of BCN prognosis.Further studies are needed to develop non-invasive diagnostic tools and establish effective treatments for BCN.
文摘BACKGROUND Diabetic nephropathy(DN)is one of the most serious microvascular complications of type 2 diabetes mellitus(T2DM),and its incidence increases with the global rise in diabetes prevalence.It is the leading cause of chronic kidney disease and end-stage kidney disease.Patients with DN often experience complex metabolic disorders and chronic inflammatory states,which not only accelerate the decline of renal function but are also closely related to complications such as cardiovascular events and osteoporosis(OP),seriously compromising quality of life.With the in-depth research on the gut microbiota and the emergence of concepts such as the"gut-kidney axis"and the"enteric-bone axis",the key roles of the gut microbiota and its metabolites in metabolic disorders,inflammatory responses,and target organ damage have been increasingly recognized.However,the specific role of gut microbiota in the pathogenesis of DN remains to be further explored.The results obtained may provide evidence to better understand the pathogenesis of DN and to identify high-risk populations at an early stage.This research direction is of strategic significance.AIM To assess the correlation of the gut microbiota metabolite trimethylamine N-oxide(TMAO)with inflammatory marker levels and OP in patients with DN.METHODS A total of 115 patients diagnosed with type 2 DN and treated at the Department of Endocrinology,Second Affiliated Hospital of Shandong First Medical University from August 2022 to December 2024 were enrolled in the DN group,and 115 patients with T2DM without nephropathy were included in the T2DM group.The two groups were compared in terms of gastrointestinal microbiota abundance and relative abundance at the genus level;levels of TMAO,inflammatory markers[including C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)],and bone metabolism markers[including procollagen type I N-terminal propeptide(PINP),β-CrossLaps(β-CTX),and alkaline phosphatase(ALP)];and lumbar spine and hip bone mineral density(BMD).The correlation of TMAO level with inflammatory factor and bone metabolism indicator levels was further analyzed.RESULTS The DN group had higher Chao1 and Simpson indices of gastrointestinal microbiota diversity than the T2DM group,whereas the ACE and Shannon indices were lower(P<0.05).The relative abundance of Firmicutes was higher,and the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria were lower in the DN group than in the T2DM group(P<0.05).CRP,IL-6,IL-8,TNF-α,and TMAO levels were considerably elevated in the DN group compared to the T2DM group(P<0.05).Moreover,the DN group had higher levels of bone turnover markers-including PINP,β-CTX,and ALP-but lower lumbar spine and hip BMDs than the T2DM group(P<0.05).TMAO level positively correlated with the Chao1 and Simpson indices and negatively correlated with the ACE and Shannon indices of gut microbiota diversity.TMAO level also negatively correlated with the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria and positively correlated with the abundance of Firmicutes.Additionally,TMAO level positively correlated with the inflammatory markers CRP,IL-6,IL-8,and TNF-α,as well as with the bone turnover markers PINP,β-CTX,and ALP.It negatively correlated with lumbar spine and hip BMDs(P<0.05).CONCLUSION Inflammatory and bone metabolic levels in patients with DN were found to be associated with the gut microbiota–derived metabolite TMAO.Elevated TMAO levels may mediate inflammatory responses and bone metabolism disorders in patients with DN,thereby contributing to the progression of systemic inflammation and OP.
基金Supported by the Natural Science Foundation of Hebei Province Beijing-Tianjin-Hebei Basic Research Special Program,No.H2020110287Key Laboratory for Diabetic Kidney Disease Syndrome and Treatment of the Traditional Chinese Medicine Administration of Hebei Province,No.7[2024]+2 种基金Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio,No.3[2024]Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications,No.SZX2020015Jiangsu Province Chinese Medicine Science and Technology Development Program Project,No.YB2020065.
文摘BACKGROUND Diabetic nephropathy(DN)is a major complication of diabetes,marked by progressive renal damage and an inflammatory response.Although research has investigated the pathological mechanisms underlying DN,effective treatment options remain limited.AIM To evaluate the therapeutic impact of Shenzhuo formulation(SZF)on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.METHODS We established a DN mouse model through a high-fat diet combined with streptozotocin(STZ)injection,followed by SZF treatment.We analyzed SZF’s effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques.Additionally,based on transcriptomic and non-targeted metabolomic findings,we further assessed SZF’s influence on the expression of factors related to the cytochrome P450(CYP450)-mediated arachidonic acid(AA)metabolism pathway,as well as its effects on inflammation and oxidative stress.RESULTS SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice.Pathological analysis revealed that SZF treatment improved renal tissue damage,reduced fibrosis,and diminished glycogen deposition.Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes,including Cyp2j13,Cyp2b9,Pla2 g2e/Cyp4a12a,Cyp4a32,Cyp2e1,and Cyp4a14.Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway,including 5,6-EET,14,15-EET,phosphatidylcholine,and 20-HETE.Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue,as well as CYP2J and CYP2B proteins.Additionally,SZF significantly reduced the expression of inflammatory factors in renal tissue,enhanced antioxidant enzyme activity,and alleviated oxidative stress.CONCLUSION SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism,leading to improved renal function and improved pathological state in DN mice.
文摘BACKGROUND The specific mechanism of diabetic nephropathy(DN)has not been fully elucidated,and more and more evidence shows that the development of DN is related to intestinal flora imbalance and micro-inflammatory state process,and this mechanism urgently needs to be further clarified by relevant research.AIM To investigate the correlation between intestinal microbiota dysbiosis,low-grade inflammatory status,renal function impairment,and disease severity in older patients with DN,in order to provide a basis for the prevention and therapeutic intervention of DN.METHODS We enrolled 167 older patients with DN,diagnosed in the Department of Nephrology between June 2020 and June 2023.Eighty-five patients with type 2 diabetes mellitus(without DN)were enrolled to serve as the control group.A one-year follow-up observation was conducted.We compared the differences in gut microbiota composition,levels of inflammatory markers,and renal function indicators between the two groups,and the characteristics of gut microbiota and the changing patterns of inflammatory markers across different stages of disease progression.RESULTS In the DN group,the Chao,Ace,and Shannon indices were significantly lower,while the Simpson index was significantly higher than the control group.The relative abundances of Bacteroides and Bifidobacterium were significantly lower,whereas the relative abundances of Clostridium,Butyricimonas,Klebsiella,Enterococcus,Veillonella,and Megamonas were significantly higher than those in the control group(P<0.05).Estimated glomerular filtration rate was positively correlated with the Chao,Ace,and Shannon diversity indices of the gut microbiota,as well as with the relative abundances of Bacteroides,Bifidobacterium,and Akkermansia,and was negatively correlated with the relative abundances of Clostridium,Klebsiella,and Enterococcus(P<0.05).Logistic regression analysis indicated that lower Chao,Ace,and Shannon indices and higher Simpson index were associated with an increased risk of developing DN.After one year of follow-up,patients in the progression group exhibited a significantly greater decrease in Chao,Ace,and Shannon indices and a greater increase in Simpson index than the stable group.The reduction in the relative abundances of Bacteroides,Clostridium,Bifidobacterium,and Butyricimonas,as well as the increase in Klebsiella,Enterococcus,Veillonella,and Megamonas,were significantly more pronounced in the progression group than in the stable group(P<0.05).Regression analysis indicated that greater declines in Chao,Ace,and Shannon indices and Bacteroides relative abundance,along with greater increases in Simpson index and Enterococcus relative abundance,were associated with a more rapid decline in renal function.CONCLUSION The onset and progression of DN in older patients with diabetes are closely associated with gut microbiota composition.The more severe the dysbiosis,the lower the abundance of beneficial bacteria and the higher the abundance of harmful bacteria,leading to an increased risk of both DN occurrence and disease progression.
文摘Diabetic nephropathy(DN)is one of the most serious complications of diabetes and a major cause of end-stage renal disease.However,due to the complexity of its pathogenesis,no new therapeutic drugs have been developed in the past 20 years,except for angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs).Breviscapine is a flavonoid active component isolated from Erigeron breviscapus,a member of the Asteraceae family.Pharmacological studies have confi rmed that this compound has antioxidant stress,anti-inflammatory regulation,anti-fibrosis and neuroprotective eff ects.Currently,it is mainly used in clinical practice as an adjuvant treatment for ischemic stroke and non-alcoholic fatty liver disease.Notably,although its antioxidant and anti-fibrotic properties have been verified in organs such as the liver and lungs,the mechanism of action in the field of DN has not been fully elucidated,especially the regulatory eff ect on the interstitial transformation of renal tubular epithelial cells remains to be revealed.Our research group has for the fi rst time systematically explored the molecular mechanism by which breviscapine improves high glucose-induced renal tubular fibrosis,providing a new theoretical basis for expanding its clinical application.
文摘Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.
文摘Objective:To explore the key points of holistic nursing for children with membranous nephropathy(MN)combined with cerebral venous thrombosis,providing a reference for similar cases.Methods:The course of illness data of an 8-year-old boy with MN in the recurrent phase complicated with cerebral venous sinus thrombosis(CVST)was retroactively analyzed.Systematic nursing was implemented based on evidence-based practices,including strict neurological monitoring,anticoagulation and thrombolysis medication nursing,fluid and electrolyte management,hypoalbuminemia and edema nursing,complication prevention,and mental health education.Results:After 16 days of continuous infusion of low molecular weight heparin and supportive treatment,the child’s symptoms,such as headache and vomiting,disappeared.The reexamination of MRV showed significant absorption of thrombosis,and there was no residual neurological deficit.During the 3-month follow-up,the anticoagulation compliance was good,and there was no recurrence.Conclusion:Early identification of hypercoagulability risk,strengthening dynamic evaluation of neurological signs and coagulation indicators,standardizing anticoagulation and thrombolysis nursing,and cooperating with continuous health management can significantly improve the prognosis of children with MN combined with CVST.
基金supported by the National Natural Science Foundation of China(Nos.82474412 and 82074364)the Innovation Program of Wuhan-Basic Research in 2022(No.2022020801020506)the Natural Science Foundation of Hubei Province(No.2022CFC024).
文摘Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-induced rat model of membranous glomerulonephritis(MGN).Methods After model establishment,Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage.A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters.Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG,C3,and Sirt1.Western blotting was performed to measure the protein levels of podocin,nephrin,Sirt1,and factors involved in the NF-κB/p65 pathway.Inflammatory cytokine levels in renal homogenates were determined by ELISA.Results Safranal at 100 or 200 mg/kg reduced kidney weight(2.07±0.15 g and 2.05±0.15 g)and the kidney somatic index(0.83±0.08%and 0.81±0.08%)in MGN rats compared with those in the model group without drug administration(2.62±0.17 g and 1.05±0.1%).C-BSA increased the urine protein level to 117.68±10.52 mg/day(compared with the sham group,5.03±0.45 mg/day),caused dysregulation of renal function indicators,and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples.All the biochemical and histological changes were improved by safranal administration.Safranal at two doses also increased the fluorescence intensities of IgG(0.1±0.009 and 0.088±0.008)and C3(0.065±0.006 and 0.048±0.004)compared with those in the MGN group(0.15±0.013 and 0.086±0.008).Additionally,safranal reversed the downregulation of podocin,nephrin,and Wilms tumor protein-1(WT1)levels and reversed the high inflammatory cytokine levels in MGN rats.Mechanistically,safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.Conclusions Safranal ameliorates renal damage,inflammation,and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.
基金Supported by the Talent Launch Fund of Chongqing Medical University Affiliated University City HospitalChongqing Medical University Affiliated University City Hospital Youth Program,No.2021ZD05.
文摘BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.
基金Supported by National Natural Science Foundation of China,No.82303047,No.82372507,No.82172196 and No.32401046Natural Science Foundation of Hunan Province,No.2022JJ40801。
文摘Diabetic nephropathy(DN)is a well-known microvascular complication in patients with diabetes mellitus,which is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments,along with the hyalinization of intrarenal vasculature.DN has recently emerged as a leading cause of chronic and end-stage renal disease.While the pathobiology of other diabetic microvascular complications,such as retinopathy,is largely understood and has reasonable therapeutic options,the mechanisms and management strategies for DN remain incompletely elucidated.In this editorial,we comment on the article by Liu et al,focusing on the mechanisms underlying the detrimental impact ofβ-arrestin-2 on the kidneys in the context of DN.The authors suggest that inhibitingβ-arrestin-2 could alleviate renal damage through suppressing apoptosis of glomerular endothelial cells(GENCs),highlightingβ-arrestin-2 as a promising therapeutic target for DN.The study proposed thatβ-arrestin-2 triggers endoplasmic reticulum(ER)stress via the ATF6 signaling pathway,thereby promoting GENC apoptosis and exacerbating DN progression.Given the novel and crucial role ofβ-arrestin-2 in ER stress-related DN,it is imperative to further exploreβ-arrestin-2,its roles in ER stress and the potential therapeutic implications in DN.
文摘Objective:To evaluate the efficacy and symptom scores of early diabetic nephropathy(DKD)treated with modified Shenqi Dihuang Decoction.Methods:82 patients with early DKD who visited the hospital from February 2023 to February 2025 were randomly divided into two groups by drawing.Group A received modified Shenqi Dihuang Decoction+SGLT2 inhibitor,while Group B received SGLT2 inhibitor only.The efficacy,symptom scores,blood glucose,and renal function were compared between the two groups.Results:The efficacy of Group A was higher than that of Group B in the treatment of early DKD(P<0.05).The DKD symptom scores of Group A were lower than those of Group B(P<0.05).The fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG),and glycated hemoglobin(HbA1c)of Group A were better than those of Group B(P<0.05).The serum creatinine(SCr),blood urea nitrogen(BUN),and urinary albumin excretion rate(UAER)of Group A were also better than those of Group B.Conclusion:The combination of modified Shenqi Dihuang Decoction and SGLT2 inhibitor dapagliflozin has excellent efficacy in the treatment of early DKD,which can improve renal function,reduce DKD symptoms,and stabilize blood glucose levels.
基金supported by the National Key Research and Development Program of China(Grant Number:2023YFC3503502)the National Natural Science Foundation of China(Grant Number:82374396).
文摘Chinese herbal medicines(CHMs)and their bioactive compounds have demonstrated clinical effectiveness in treating and managing membranous nephropathy(MN),as evidenced by a comprehensive analysis of clinical trials,systematic reviews,and meta-analyses.The bioactive constituents of CHMs exert their therapeutic effects by modulating various signaling pathways,resulting in antioxidant,anti-inflammatory,and antifibrotic properties,as well as the regulation of autophagy.In contrast to conventional single-target approaches,traditional Chinese medicines formulas and phytochemicals employ a multi-target therapeutic strategy for MN,which has shown significant clinical efficacy and the potential to mitigate or reverse the damage.This evaluation provides a foundation for a comprehensive clinical understanding of the protective role of CHMs in the context of MN,highlighting their benefits and prospects in addressing this condition.
基金funded by National Natural Science Foundation of China,No.811734071The Fundamental Research Funds for the Central Universities(2023-JYB-XJSJJ043)The fifth batch of National TCM Clinical Outstanding Talents Training Program(National TCM Personnel Education Letter[2022]No.1)。
文摘Background:Hypertensive nephropathy remains a leading cause of end-stage renal disease with limited targeted therapies.Methods:We conducted a bibliometric analysis(1992-2024)of 440 basic studies from 7 databases,using VOSviewer and R to quantify research evolution.Intervention modalities,signaling pathways,and mechanisms were innovatively extracted.Results:Quantified analysis revealed a distinct temporal evolution:early research was dominated by TGF-βsignaling,while starting from 2015,the focus of the research turned to podocyte-targeted studies.Traditional Chinese medicine compounds emerged as the predominant intervention,yet standardization deficits persisted across 73 formulas.Despite limited human pathological concordance,Spontaneously hypertensive rats models were utilized in most studies.Critically,only a few podocyte-focused therapeutics advanced to clinical trials,primarily hindered by species-specific Transient receptor potential channel expression divergence and mesenchymal stem cells renal delivery.Conclusion:Podocyte protection and standardized traditional Chinese medicine are potential translational targets,but there is a lack of reliable clinical trials for clinical verification.
文摘Objective:To evaluate the therapeutic effect of Shenqi Dihuang Decoction combined with calcium dobesilate on patients with diabetic nephropathy(DKD).Methods:90 patients with DKD who visited the hospital from March 2024 to March 2025 were selected as samples and randomly divided into two groups.Group A was treated with Shenqi Dihuang Decoction combined with calcium dobesilate,while Group B was treated with calcium dobesilate alone.The efficacy,syndrome scores,blood glucose levels,and renal function indicators were compared between the two groups.Results:The efficacy of DKD treatment in Group A was higher than that in Group B(P<0.05).The syndrome scores in Group A were lower than those in Group B(P<0.05).The 2-hour postprandial blood glucose(PBG),fasting blood glucose(FBG),and glycated hemoglobin(HbA1c)levels in Group A were lower than those in Group B(P<0.05).The serum creatinine(SCr),urinary microalbumin,urinary albumin excretion rate(UAER),and β2-microglobulin(β2-MG)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:The treatment of DKD with Shenqi Dihuang Decoction combined with calcium dobesilate can stabilize blood glucose levels,improve renal function,and reduce syndrome scores,which is highly effective and feasible.
文摘BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of microRNAs(e.g.,miR-495-3p),adiponectin(ADPN),and cardiometabolic index(CMI)in metabolic and renal pathologies.However,their combined predictive value for T2DN prognosis is not well understood.AIM To explore serum miR-495-3p,ADPN,and CMI levels in T2DN and their value in predicting prognosis.METHODS A total of 98 T2DN patients(study group)and 49 type 2 diabetic patients with normal renal function(control group)were enrolled from February 2020 to February 2022.Serum levels of miR-495-3p,ADPN,and CMI were measured in both groups.Patients were followed up for 6 months to assess prognosis.Dif-ferences between groups were analyzed,and multivariate logistic regression and receiver operating characteristic(ROC)curve analyses were performed to eva-luate the predictive value of these biomarkers.RESULTS The study group exhibited significantly lower miR-495-3p levels and higher ADPN and CMI levels compared to the control group(P<0.05).Poor prognosis patients had even lower miR-495-3p and higher ADPN and CMI levels than those with good prognosis(P<0.05).Multivariate analysis identified alanine amino-transferase,aspartate aminotransferase,urea nitrogen,serum creatinine,miR-495-3p,ADPN,and CMI as independent predictors of prognosis(P<0.05).ROC analysis revealed area under the curve values of 0.762(miR-495-3p),0.902(ADPN),0.757(CMI),0.899(alanine aminotransferase),0.852(aspartate ami-notransferase),0.916(urea nitrogen),and 0.910(serum creatinine)for predicting poor prognosis(P<0.05).CONCLUSION Low miR-495-3p and high ADPN and CMI levels are linked to T2DN and poor prognosis,highlighting their potential for risk prediction and clinical management.
基金Shandong Province Traditional Chinese Medicine Science and Technology Project(Project No.M-2023290)。
文摘Objective:To evaluate the efficacy of the modified Gui Fu Ling Wu Decoction in treating diabetic nephropathy(DN)of the spleen-kidney Yang deficiency type.Methods:A total of 100 DN patients admitted to Changyi Traditional Chinese Medicine Hospital between August 2023 and March 2024 were included in the study.Patients were randomly divided into a control group and a study group,each comprising 50 cases,using a computerized random number generator.The control group received kallikrein treatment,while the study group received a combination of kallikrein and the modified Gui Fu Ling Wu Decoction.Blood glucose control,renal function,and inflammatory markers were assessed before and after treatment in both groups.Results:Before treatment,there were no significant differences in blood glucose and renal function indicators between the two groups(P>0.05).After treatment,postprandial blood glucose,fasting blood glucose,24-hour urinary protein,urinary microalbumin,serum creatinine,serum C-reactive protein(CRP),and interleukin-6 levels significantly decreased in both groups,with the study group showing superior results compared to the control group(P<0.05).Conclusion:The combination of Gui Fu Ling Wu Decoction and kallikrein for treating spleen-kidney Yang deficiency type DN significantly improves blood glucose control,enhances renal function,and reduces inflammatory responses.
基金supported by the Natural Science Foundation of China(82560923)Natural Science Foundation of InnerMongolia(2019MS08008)+1 种基金Natural Science Foundation of Inner Mongolia Joint Program(2023LHMS08075)General Project of Inner Mongolia Medical University(YKD2025MS026).
文摘Objective Forsythia suspensa has long been utilized in traditional Chinese medicine(TCM)for the treatment of IgA nephropathy(IgAN),the most prevalent form of primary glomerular disease.However,the precise mechanisms remain inadequately understood.This study seeks to elucidate the underlying mechanisms of Forsythia suspensa extract(FSE)in the treatment of IgAN by employing an integrated approach that combines network pharmacology with in vivo experimental validation.Methods The chemical components of FSE were identified using high-performance liquid chromatography-mass spectrometry(HPLC–MS/MS).Additional chemical components and targets were determined through the Traditional Chinese Medicine Systems Pharmacology database.Potential therapeutic targets for IgAN were sourced from GeneCards and the Comparative Toxicogenomics Database.Subsequently,the enrichment analyses were conducted to evaluate the biological functions and pathways associated with the core targets.Finally,a mousemodel of IgAN was developed to validate the findings of the network pharmacology analysis.Results Through network analysis and HPLC–MS/MS,31 chemical components of FSE were identified.A total of 99 common targets were discovered between FSE and IgAN.The enrichment analyses suggested that FSE may mitigate IgAN primarily by inhibiting the TLR and NF-κB signaling pathways.In vivo experiments demonstrated that FSE reduced inflammation and preserved renal function in mice with IgAN through the Tolllike receptor 9(TLR9)/NF-κB pathway.Conclusion The integration of network pharmacology and animal experiments suggests that FSE alleviates renal inflammation and damage in IgAN through the TLR9/NF-κB signaling pathway.
文摘Objective:To investigate the clinical efficacy of traditional Chinese medicine(TCM)syndrome differentiation in the treatment of patients with gouty nephropathy.Methods:From June 2023 to December 2024,80 patients with gouty nephropathy were selected as samples and randomly divided into two groups:group A received TCM syndrome differentiation treatment,while group B received conventional treatment.The efficacy,laboratory indicators,symptom scores,and safety were compared between the two groups.Results:The efficacy of group A was higher than that of group B(P<0.05).The uric acid,blood urea nitrogen,serum creatinine,and 24-hour urinary protein levels in group A were lower than those in group B(P<0.05).The symptom score of group A was lower than that of group B(P<0.05).The adverse reactions of gouty nephropathy in group A were lower than those in group B(P<0.05).Conclusion:TCM syndrome differentiation treatment for gouty nephropathy can alleviate symptoms,protect renal function,and is highly effective and feasible.
基金supported by grants from the Open Grant from the Pingyuan Laboratory(No.2023PYOP-0203)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2023QNRC001)+1 种基金Beijing Natural Science Foundation(No.7244407)National Natural Science Foundation of China(Nos.82400846 and 82274327).
文摘Objective Th17 cell-mediated immune injury is a crucial factor contributing to tubulointerstitial fibrosis in patients with IgA nephropathy(IgAN).However,the exact mechanisms by which Th17 cells induce tubulointerstitial fibrosis remain to be fully elucidated.Methods An IgAN mouse model was established and validated.Transcriptome sequencing,combined with bioinformatics analysis,was carried out to explore the immune injury pathways in renal tissues and the activation pathways in Th17 cells that were co-cultured with tubular epithelial cells.In subsequent experiments,small interfering RNA(siRNA)and overexpression plasmids were used to manipulate cellular targets.Validation was conducted through quantitative real-time polymerase chain reaction(qPCR),Western blotting,and immunofluorescence assays.Results Compared with the control mice,IgAN mice exhibited elevated serum creatinine levels and increased urine protein-to-creatinine ratios.Renal pathological examination revealed the characteristic features of IgAN.Transcriptomic analysis of the kidney tissues from the model mice showed the activation of Th17 differentiation pathways,which was further confirmed by immunofluorescence analysis showing increased expression of interleukin-17A(IL-17A).These findings indicate an increased abundance of Th17 cells with potential pathogenic significance.When Th17 cells were co-cultured with tubular epithelial cells,the level of interleukin-9(IL-9)in the system increased.This increase in IL-9 activated the Janus kinase 1-signal transducer and activator of transcription 3(JAK1-STAT3)pathway through the IL-9 receptor(IL-9R)and upregulated the signature transcription factor retinoic acid-related orphan receptor gamma(ROR-γ),thus promoting Th17 cell differentiation.When IL-9R was silenced using siRNA or when the activity of STAT3 was inhibited,both the levels of phosphorylated STAT3(p-STAT3)and ROR-γdecreased.Moreover,IL-17A secreted by Th17 cells promoted the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)in tubular epithelial cells by activating the IL-17 receptor A(IL-17RA)–adaptor protein Act1–tumor necrosis factor receptor-associated factor 6(TRAF6)complex.This process regulated the production of inflammatory cytokines and drove the initiation and progression of fibrosis.Treatment with a STAT3 inhibitor in IgAN mice led to a reduction in the number of renal Th17 cells and alleviated the fibrotic phenotype.Conclusion This study demonstrated that the interaction between Th17 cells and tubular epithelial cells triggers excessive extracellular matrix deposition in the tubulointerstitium,thereby exacerbating the fibrotic phenotype and accelerating the progression of IgAN.
