Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
Medical Data Mining published an article entitled Mapping the global research trends and hotspots on hypertensive nephropathy:A novel bibliometrics overview on 10 October 2025.The author confirmed this article’s proo...Medical Data Mining published an article entitled Mapping the global research trends and hotspots on hypertensive nephropathy:A novel bibliometrics overview on 10 October 2025.The author confirmed this article’s proof on 28 September 2025 without any questions.However,on 13 November 2025,the Editorial Office of Medical Data Mining noticed an inconsistency between the data presented in the main text and Figure 1.Specifically,erroneous Figure 1 states“a total of 56,691 literatures were obtained through database search”,while the main text in the Search results section states“According to the search term,a total of 59,220 publications were retrieved from the database.”The authors acknowledge that the original version of Figure 1 was incorrect and have provided the revised,correct version in this corrigendum.The authors would like to assert that there is no change in the body text of the article.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
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
Objective IgA nephropathy(IgAN)is the most prevalent form of primary glomerular disease.However,its diagnosis is contingent on kidney biopsy.Therefore,noninvasive biomarkers are urgently needed for diagnosis.This stud...Objective IgA nephropathy(IgAN)is the most prevalent form of primary glomerular disease.However,its diagnosis is contingent on kidney biopsy.Therefore,noninvasive biomarkers are urgently needed for diagnosis.This study aims to identify novel urinary biomarkers that differentiate IgAN from other common primary glomerular diseases,specifically membranous nephropathy(MN)and minimal change disease(MCD).Methods The peripheral blood mononuclear cell(PBMC)transcriptome dataset GSE73953 was obtained from the GEO database.Differential gene expression,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,Gene Ontology(GO)enrichment,and immune infiltration analyses were performed.Protein–protein interaction(PPI)analysis and lysosome-related genes were used to identify hub genes.The expression of the hub gene ATP6V1D in urine and kidney tissues from individuals with IgAN,healthy controls,MCD and MN patients was assessed using enzyme-linked immunosorbent assay(ELISA),Western blotting,and immunostaining techniques.Spearman’s correlation analysis was employed to investigate the relationships between the concentration of ATP6V1D in urine,the concentration of galactose-deficient IgA1(GD-IgA1),and the clinical data of patients.The receiver operating characteristic(ROC)curve was used to assess the role of urine ATP6V1D levels in distinguishing IgAN from MN and MCD.Results ATPase was identified as the principal intracellular structure associated with differentially expressed genes(DEGs)between IgAN patients and healthy controls in PBMCs.ATP6V1D was identified as a hub gene at the intersection of lysosome-related and differential genes.ATP6V1D levels were lower in PBMCs,urine,and kidney samples from IgAN patients than in those from healthy individuals,MCD and MN patients.The decreased urinary ATP6V1D levels and increased GD-IgA1 levels in IgAN patients were further validated.These changes were positively correlated with 24-h urine protein levels.Notably,a negative correlation was observed between ATP6V1D and GD-IgA1 levels.ROC curve analysis demonstrated that urinary ATP6V1D(AUC=0.972)and GD-IgA1(AUC=0.952)had significant discriminative power in distinguishing IgAN patients from MCD and MN patients,with no significant difference in predictive performance between the two biomarkers(P>0.05).Conclusions The findings underscore the potential utility of the urine ATP6V1D concentration as a biomarker to distinguish IgAN from MN and MCD.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
This article comments on Varatharajan et al recent article,highlighting the role of tubulointerstitial damage mechanisms in diabetic nephropathy progression.Evidence suggests a bidirectional interaction between the in...This article comments on Varatharajan et al recent article,highlighting the role of tubulointerstitial damage mechanisms in diabetic nephropathy progression.Evidence suggests a bidirectional interaction between the interstitium,tubular cells,and glomeruli.Renal tubules are highly susceptible to proteinuria,metabolic disorders,and toxins.Since diabetic nephropathy persistently activates inflammatory and fibrotic pathways,epithelial-to-mesenchymal transition mechanisms present promising targets for risk assessment.Periostin,a cellular matrix protein,plays a key role in modulating extracellular interactions.Increased periostin expression in tissue,serum,and urine correlates with type 2 diabetes,making it a valuable biomarker alongside neutrophil gelatinase-associated lipocalin and kidney injury molecule-1.While periostin and neutrophil gelatinase-associated lipocalin reflect distal tubular damage,kidney injury molecule-1 serves as a marker for proximal tubular injury.Combining these biomarkers enhances diagnostic precision.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 Background diabetic nephropathy(DN),a major complication of diabetes,is linked to gut microbiota dysbiosis.Elevated trimethylamine N-oxide(TMAO),a microbiota-derived metabolite,plays a central role in induc...BACKGROUND Background diabetic nephropathy(DN),a major complication of diabetes,is linked to gut microbiota dysbiosis.Elevated trimethylamine N-oxide(TMAO),a microbiota-derived metabolite,plays a central role in inducing renal injury during DN pathogenesis.AIM To investigate the role of TMAO in renal dysfunction and intestinal microbiota alterations associated with DN,hypothesizing that TMAO exacerbates renal injury and fibrosis through gut microbiota-dependent mechanisms.METHODS A DN model was successfully established using Zucker diabetic fatty(ZDF)rats.Blood samples were analyzed for renal function parameters,and serum TMAO levels were quantified via high-performance liquid chromatography-tandem mass spectrometry.Renal tissue morphology and fibrosis were assessed using hematoxylin and eosin and Masson staining,respectively.Additionally,16S rRNA sequencing was employed to profile fecal bacterial communities in rats with diabetes and DN.Fecal microbiota transplantation was conducted to verify alterations in TMAO production capacity in the gut microbiota of DN rats.RESULTS After 8 weeks of modeling,the ZDF rat model group exhibited blood glucose levels surpassing 16.7 mmol/L,and compared to the control group,renal function indicators,includingβ2-microglobulin,cystatin C,uric acid,and creatinine,were significantly elevated(P<0.05).Renal fibrosis was more pronounced in the ZDF model group,accompanied by heightened P-smad3 expression,in contrast to the TMAO inhibition group.Although Masson staining results did not reach statistical significance(P>0.05),notable alterations in intestinal flora structure were observed in DN rats,and fecal microbiota transplantation led to increased TMAO production within the intestinal flora of DN rats compared to controls(P>0.05).CONCLUSION DN is associated with gut microbiota alterations that potentiate TMAO generation,contributing to renal injury and fibrotic progression.While TMAO’s role in fibrosis warrants further validation,these findings implicate the gutkidney axis in DN pathogenesis.展开更多
Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy(DN).Growing evidence highlights the pivotal role of paired-related homeobox 1(Prrx1),a key regulator of cellular proliferation an...Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy(DN).Growing evidence highlights the pivotal role of paired-related homeobox 1(Prrx1),a key regulator of cellular proliferation and tissue differentiation,in various disease pathogenesis.Notably,Prrx1 is highly expressed in mesangial cells under DN conditions.Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice.Conversely,Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell prolif-eration and mitigates renal fibrosis in db/db mice.Mechanistically,Prrx1 directly interacts with the Yes-associated protein 1(YAP)promoter,leading to the upregulation of YAP expression.This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis.These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation,ultimately leading to renal fibrosis in DN.Therefore,targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with 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
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 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: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
OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-perfo...OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN,which were subsequently validated through in vivo experiments.Sixty male Bagg Albino Laboratory-Bred Mouse,substrain c mice were randomly allocated into six groups:Normal,Model,Febuxostat,and three SZF dosage groups.Except for the Normal group,all mice were administered potassium oxonate(250 mg/kg)and adenine(50 mg/kg)via gavage to induce UAN.Four hours postadministration,the Febuxostat group received Febuxostat(6 mg/kg),while the SZF groups received low(0.234 g/kg),medium(0.468 g/kg),or high(0.936 g/kg)doses of SZF.The Normal and Model groups were given an equivalent volume of saline.All treatments were conducted over a period of four weeks.Urine and blood samples were collected for biochemical analysis,and kidney tissues were subjected to histopathological examination and Western blot analysis.RESULTS:Nine prototype compounds and 30 metabolites were identified in SZF serum.Network pharmacology analysis revealed 195 drug targets and 1608 disease targets,with 76 common drug-disease targets,including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),matrix metalloproteinase-9(MMP9),Caspase 3,and toll-like receptor 4(TLR4)as key targets.Gene Ontology analysis identified 325 biological processes,48 cellular components,and 72 molecular functions,while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways.Molecular docking demonstrated strong binding affinities between active compounds and their targets.In the animal study,SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group(P<0.05,P<0.01,P<0.001).Western blot analysis showed a significant reduction in phosphorylated-STAT3,phosphorylatedSRC,MMP9,TLR4,and Caspase3 expression in renal tissues of SZF-treated mice(P<0.001).CONCLUSION:SZF may exert therapeutic effects on UAN through multiple targets and pathways.展开更多
BACKGROUND The coexistence of rheumatological and immunological diseases with nephropathy presents considerable clinical challenges.These challenges often result in heightened anxiety and depression,which detrimentall...BACKGROUND The coexistence of rheumatological and immunological diseases with nephropathy presents considerable clinical challenges.These challenges often result in heightened anxiety and depression,which detrimentally affect patient outcomes.Motivational psychological nursing,which incorporates motivational interview and cognitive-behavioral therapy,may offer a promising approach to address these psychological concerns.AIM To evaluate the effectiveness of motivational psychological nursing in the reduction of anxiety and depression and improvement of the quality of life of patients with rheumatological and immunological diseases complicated by nephropathy.METHODS We conducted a retrospective cohort study involving 206 patients with rheumatological and immunological diseases complicated by nephropathy and who were treated between January 2021 and January 2025.The inclusion criteria were as follows:Aged 18-75 years,met the diagnostic criteria for rheumatological and immunological diseases with a renal biopsy classification above type II,hospitalized in our facility,received consistent basic nursing care,and had complete clinical data available.Participants allotted to the observation group(n=102)receiving motivational psychological nursing,and those in the control group(n=104)received standard care.Psychological status was assessed using Self-Rating Anxiety Scale(SAS),Beck Anxiety Inventory,Hamilton Anxiety Rating Scale,Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9,and other standardized measures.Intervention lasted throughout hospitalization,with follow-up assessments conducted before discharge.RESULTS Pre-intervention,anxiety,and depression scores were similar across groups.Postintervention,the observation group showed significant reductions in anxiety(SAS:44.53±6.72 vs 46.79±6.94;P=0.018)and depression(SDS:45.20±5.07 vs 46.97±5.25;P=0.014)compared with the control group.General self-efficacy(P=0.044),healthrelated quality of life(P=0.044),and World Health Organization Quality of Life(P=0.040)scores also revealed significant improvement.CONCLUSION Motivational psychological nursing considerably reduces anxiety and depression in patients with rheumatological and immunological diseases complicated by nephropathy,which enhances the overall quality of life.展开更多
Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke ...Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction(XKD),a traditional Chinese medicine,on renal function in DN rats.Methods A rat model of DN was established,and the rats were divided into five groups(n=7 per group):normal control group(NC),DN model group(DN),low-dose XKD treatment group(DN+XKD-L,1.5 g/kg/d),high-dose XKD treatment group(DN+XKD-H,6 g/kg/d),and cyclooxygenase-2(COX-2)inhibitor(NS398)treatment group(DN+NS398,8 mg/kg/d).Medications were administered via gavage for 12 consecutive weeks,while equal volumes of normal saline were given to the NC and DN groups.A glucometer was used to detect changes in blood glucose(BG).Enzyme-linked immunosorbent assay(ELISA)and an automatic biochemical analyzer were employed to measure levels of insulin,serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and 24-h urine protein quantity(UP/24 h)in rats.Renal tissue sections from different treatment groups were prepared,with tissue lesions examined via periodic acid-Schiff(PAS)and hematoxylin–eosin(HE)staining.Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining.Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor(LDLr)in tissues,and to clarify the regulatory mechanism of XKD on renal function in DN rats.Results XKD,particularly at the high dose(XKD-H,6 g/kg/d),significantly reduced BG,insulin levels,renal weight ratio,Scr,BUN,and UP/24 h in DN rats.DN rats showed significant renal lesions,and XKD gavage(especially XKD-H)markedly improved these pathological changes.In DN rats,XKD significantly decreased the protein expression levels of COX-2 and LDLr,downregulated the levels of inflammatory factors and lipid factors,reduced lipid deposition in renal tissues,and ameliorated structural abnormalities in glomeruli,basement membranes,and renal tubules.Conclusions XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway,thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.Graphical Abstract XKD improves renal function in streptozotocin(STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway,reducing inflammatory factors and lipid deposition,and alleviating renal tissue damage.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 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
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
文摘Medical Data Mining published an article entitled Mapping the global research trends and hotspots on hypertensive nephropathy:A novel bibliometrics overview on 10 October 2025.The author confirmed this article’s proof on 28 September 2025 without any questions.However,on 13 November 2025,the Editorial Office of Medical Data Mining noticed an inconsistency between the data presented in the main text and Figure 1.Specifically,erroneous Figure 1 states“a total of 56,691 literatures were obtained through database search”,while the main text in the Search results section states“According to the search term,a total of 59,220 publications were retrieved from the database.”The authors acknowledge that the original version of Figure 1 was incorrect and have provided the revised,correct version in this corrigendum.The authors would like to assert that there is no change in the body text of the article.
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.
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.
基金supported by the Science and Technology Innovation Project of Hunan Province(No.2020SK51601)the Health Commission of Hunan Province Scientific Research Projects(No.202203054127)the Science and Technology Plan of Loudi City(No.202202).
文摘Objective IgA nephropathy(IgAN)is the most prevalent form of primary glomerular disease.However,its diagnosis is contingent on kidney biopsy.Therefore,noninvasive biomarkers are urgently needed for diagnosis.This study aims to identify novel urinary biomarkers that differentiate IgAN from other common primary glomerular diseases,specifically membranous nephropathy(MN)and minimal change disease(MCD).Methods The peripheral blood mononuclear cell(PBMC)transcriptome dataset GSE73953 was obtained from the GEO database.Differential gene expression,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,Gene Ontology(GO)enrichment,and immune infiltration analyses were performed.Protein–protein interaction(PPI)analysis and lysosome-related genes were used to identify hub genes.The expression of the hub gene ATP6V1D in urine and kidney tissues from individuals with IgAN,healthy controls,MCD and MN patients was assessed using enzyme-linked immunosorbent assay(ELISA),Western blotting,and immunostaining techniques.Spearman’s correlation analysis was employed to investigate the relationships between the concentration of ATP6V1D in urine,the concentration of galactose-deficient IgA1(GD-IgA1),and the clinical data of patients.The receiver operating characteristic(ROC)curve was used to assess the role of urine ATP6V1D levels in distinguishing IgAN from MN and MCD.Results ATPase was identified as the principal intracellular structure associated with differentially expressed genes(DEGs)between IgAN patients and healthy controls in PBMCs.ATP6V1D was identified as a hub gene at the intersection of lysosome-related and differential genes.ATP6V1D levels were lower in PBMCs,urine,and kidney samples from IgAN patients than in those from healthy individuals,MCD and MN patients.The decreased urinary ATP6V1D levels and increased GD-IgA1 levels in IgAN patients were further validated.These changes were positively correlated with 24-h urine protein levels.Notably,a negative correlation was observed between ATP6V1D and GD-IgA1 levels.ROC curve analysis demonstrated that urinary ATP6V1D(AUC=0.972)and GD-IgA1(AUC=0.952)had significant discriminative power in distinguishing IgAN patients from MCD and MN patients,with no significant difference in predictive performance between the two biomarkers(P>0.05).Conclusions The findings underscore the potential utility of the urine ATP6V1D concentration as a biomarker to distinguish IgAN from MN and MCD.
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This article comments on Varatharajan et al recent article,highlighting the role of tubulointerstitial damage mechanisms in diabetic nephropathy progression.Evidence suggests a bidirectional interaction between the interstitium,tubular cells,and glomeruli.Renal tubules are highly susceptible to proteinuria,metabolic disorders,and toxins.Since diabetic nephropathy persistently activates inflammatory and fibrotic pathways,epithelial-to-mesenchymal transition mechanisms present promising targets for risk assessment.Periostin,a cellular matrix protein,plays a key role in modulating extracellular interactions.Increased periostin expression in tissue,serum,and urine correlates with type 2 diabetes,making it a valuable biomarker alongside neutrophil gelatinase-associated lipocalin and kidney injury molecule-1.While periostin and neutrophil gelatinase-associated lipocalin reflect distal tubular damage,kidney injury molecule-1 serves as a marker for proximal tubular injury.Combining these biomarkers enhances diagnostic precision.
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 Chinese People’s Liberation Army,No.2021yxky056.
文摘BACKGROUND Background diabetic nephropathy(DN),a major complication of diabetes,is linked to gut microbiota dysbiosis.Elevated trimethylamine N-oxide(TMAO),a microbiota-derived metabolite,plays a central role in inducing renal injury during DN pathogenesis.AIM To investigate the role of TMAO in renal dysfunction and intestinal microbiota alterations associated with DN,hypothesizing that TMAO exacerbates renal injury and fibrosis through gut microbiota-dependent mechanisms.METHODS A DN model was successfully established using Zucker diabetic fatty(ZDF)rats.Blood samples were analyzed for renal function parameters,and serum TMAO levels were quantified via high-performance liquid chromatography-tandem mass spectrometry.Renal tissue morphology and fibrosis were assessed using hematoxylin and eosin and Masson staining,respectively.Additionally,16S rRNA sequencing was employed to profile fecal bacterial communities in rats with diabetes and DN.Fecal microbiota transplantation was conducted to verify alterations in TMAO production capacity in the gut microbiota of DN rats.RESULTS After 8 weeks of modeling,the ZDF rat model group exhibited blood glucose levels surpassing 16.7 mmol/L,and compared to the control group,renal function indicators,includingβ2-microglobulin,cystatin C,uric acid,and creatinine,were significantly elevated(P<0.05).Renal fibrosis was more pronounced in the ZDF model group,accompanied by heightened P-smad3 expression,in contrast to the TMAO inhibition group.Although Masson staining results did not reach statistical significance(P>0.05),notable alterations in intestinal flora structure were observed in DN rats,and fecal microbiota transplantation led to increased TMAO production within the intestinal flora of DN rats compared to controls(P>0.05).CONCLUSION DN is associated with gut microbiota alterations that potentiate TMAO generation,contributing to renal injury and fibrotic progression.While TMAO’s role in fibrosis warrants further validation,these findings implicate the gutkidney axis in DN pathogenesis.
基金the National Natural Science Foundation of China(Grant Nos.:82273987,81973377,82073906)PostgraduateResearch Practice Innovation Program of Jiangsu Province(Grant No.:KYCX23_2994)+1 种基金the data provided by the GEO database,and the single cell analysis provided by the KIT platform.KOBAs for its contribution to the data analysis.
文摘Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy(DN).Growing evidence highlights the pivotal role of paired-related homeobox 1(Prrx1),a key regulator of cellular proliferation and tissue differentiation,in various disease pathogenesis.Notably,Prrx1 is highly expressed in mesangial cells under DN conditions.Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice.Conversely,Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell prolif-eration and mitigates renal fibrosis in db/db mice.Mechanistically,Prrx1 directly interacts with the Yes-associated protein 1(YAP)promoter,leading to the upregulation of YAP expression.This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis.These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation,ultimately leading to renal fibrosis in DN.Therefore,targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with 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 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.
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.
基金National Science Foundation of China:Mechanistic Study on How Shizhi Fang Promotes Mitocytosis of Renal Tubular Epithelial Cells to Alleviate Hyperuricemia-Induced Kidney Injury(82274415)National Science Foundation of China:Mechanistic Study on Shizhi Fang in Lowering Uric Acid Based on Extracellular Signal-regulated Kinases 1 and 2-mediated Transcriptional Regulation of the Uric Acid Transporter Urate Transporter 1(82474434)。
文摘OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN,which were subsequently validated through in vivo experiments.Sixty male Bagg Albino Laboratory-Bred Mouse,substrain c mice were randomly allocated into six groups:Normal,Model,Febuxostat,and three SZF dosage groups.Except for the Normal group,all mice were administered potassium oxonate(250 mg/kg)and adenine(50 mg/kg)via gavage to induce UAN.Four hours postadministration,the Febuxostat group received Febuxostat(6 mg/kg),while the SZF groups received low(0.234 g/kg),medium(0.468 g/kg),or high(0.936 g/kg)doses of SZF.The Normal and Model groups were given an equivalent volume of saline.All treatments were conducted over a period of four weeks.Urine and blood samples were collected for biochemical analysis,and kidney tissues were subjected to histopathological examination and Western blot analysis.RESULTS:Nine prototype compounds and 30 metabolites were identified in SZF serum.Network pharmacology analysis revealed 195 drug targets and 1608 disease targets,with 76 common drug-disease targets,including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),matrix metalloproteinase-9(MMP9),Caspase 3,and toll-like receptor 4(TLR4)as key targets.Gene Ontology analysis identified 325 biological processes,48 cellular components,and 72 molecular functions,while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways.Molecular docking demonstrated strong binding affinities between active compounds and their targets.In the animal study,SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group(P<0.05,P<0.01,P<0.001).Western blot analysis showed a significant reduction in phosphorylated-STAT3,phosphorylatedSRC,MMP9,TLR4,and Caspase3 expression in renal tissues of SZF-treated mice(P<0.001).CONCLUSION:SZF may exert therapeutic effects on UAN through multiple targets and pathways.
文摘BACKGROUND The coexistence of rheumatological and immunological diseases with nephropathy presents considerable clinical challenges.These challenges often result in heightened anxiety and depression,which detrimentally affect patient outcomes.Motivational psychological nursing,which incorporates motivational interview and cognitive-behavioral therapy,may offer a promising approach to address these psychological concerns.AIM To evaluate the effectiveness of motivational psychological nursing in the reduction of anxiety and depression and improvement of the quality of life of patients with rheumatological and immunological diseases complicated by nephropathy.METHODS We conducted a retrospective cohort study involving 206 patients with rheumatological and immunological diseases complicated by nephropathy and who were treated between January 2021 and January 2025.The inclusion criteria were as follows:Aged 18-75 years,met the diagnostic criteria for rheumatological and immunological diseases with a renal biopsy classification above type II,hospitalized in our facility,received consistent basic nursing care,and had complete clinical data available.Participants allotted to the observation group(n=102)receiving motivational psychological nursing,and those in the control group(n=104)received standard care.Psychological status was assessed using Self-Rating Anxiety Scale(SAS),Beck Anxiety Inventory,Hamilton Anxiety Rating Scale,Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9,and other standardized measures.Intervention lasted throughout hospitalization,with follow-up assessments conducted before discharge.RESULTS Pre-intervention,anxiety,and depression scores were similar across groups.Postintervention,the observation group showed significant reductions in anxiety(SAS:44.53±6.72 vs 46.79±6.94;P=0.018)and depression(SDS:45.20±5.07 vs 46.97±5.25;P=0.014)compared with the control group.General self-efficacy(P=0.044),healthrelated quality of life(P=0.044),and World Health Organization Quality of Life(P=0.040)scores also revealed significant improvement.CONCLUSION Motivational psychological nursing considerably reduces anxiety and depression in patients with rheumatological and immunological diseases complicated by nephropathy,which enhances the overall quality of life.
基金supported by the Budget Project of Shanghai University of Traditional Chinese Medicine(18LK058).
文摘Objective Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy(DN).This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction(XKD),a traditional Chinese medicine,on renal function in DN rats.Methods A rat model of DN was established,and the rats were divided into five groups(n=7 per group):normal control group(NC),DN model group(DN),low-dose XKD treatment group(DN+XKD-L,1.5 g/kg/d),high-dose XKD treatment group(DN+XKD-H,6 g/kg/d),and cyclooxygenase-2(COX-2)inhibitor(NS398)treatment group(DN+NS398,8 mg/kg/d).Medications were administered via gavage for 12 consecutive weeks,while equal volumes of normal saline were given to the NC and DN groups.A glucometer was used to detect changes in blood glucose(BG).Enzyme-linked immunosorbent assay(ELISA)and an automatic biochemical analyzer were employed to measure levels of insulin,serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and 24-h urine protein quantity(UP/24 h)in rats.Renal tissue sections from different treatment groups were prepared,with tissue lesions examined via periodic acid-Schiff(PAS)and hematoxylin–eosin(HE)staining.Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining.Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor(LDLr)in tissues,and to clarify the regulatory mechanism of XKD on renal function in DN rats.Results XKD,particularly at the high dose(XKD-H,6 g/kg/d),significantly reduced BG,insulin levels,renal weight ratio,Scr,BUN,and UP/24 h in DN rats.DN rats showed significant renal lesions,and XKD gavage(especially XKD-H)markedly improved these pathological changes.In DN rats,XKD significantly decreased the protein expression levels of COX-2 and LDLr,downregulated the levels of inflammatory factors and lipid factors,reduced lipid deposition in renal tissues,and ameliorated structural abnormalities in glomeruli,basement membranes,and renal tubules.Conclusions XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway,thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.Graphical Abstract XKD improves renal function in streptozotocin(STZ)-induced DN rats by regulating the COX-2-mediated LDLr pathway,reducing inflammatory factors and lipid deposition,and alleviating renal tissue damage.
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.
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.
