Exploring the Impact of Optimized Probiotic Supplementation Techniques on Diabetic Nephropathy: Mechanisms and Therapeutic Potential.

Worldwide, diabetic nephropathy (DN) is a significant contributor to end-stage renal failure and chronic kidney disease. Probiotic supplementation has recently gained popularity as a potential nutritional therapy in several clinical trials aimed at improving renal function, inflammation, oxidative stress, dyslipidemia, glycemic control, and inflammation. However, they still need to undergo a thorough assessment of DN. It is crucial that the optimal dosage, duration, and combination of probiotic strains administered for the purpose of slowing down the advancement of DN be assessed. Based on the available publications, including relevant randomized controlled trials, systematic reviews, and meta-analysis from 2013-2023 from search engines like MEDLINE (PubMed), Scopus, and Web of Science, a literature review was generated using the keywords "gut microbiota," "gut microbiome," "diabetic kidney disease," "diabetic nephropathy," "probiotic," and "prebiotic." Multiple clinical trials focusing on probiotic administration techniques revealed changes in renal, glucose, and lipid biomarkers. Probiotic supplementation using Bifidobacterium bifidum, Lactobacillus acidophilus, and Streptococcus thermophilus for 12 weeks indicated a reduction in glycosylated hemoglobin, fasting blood glucose, and the microalbuminuria/creatinine ratio. Multispecies as well as single-species probiotic administration containing Lactobacillus, Bifidobacterium, and Streptococcus thermophilus spp. greater than 4*109 colony forming units (CFU)/day for 8-12 weeks in DN patients improves renal metabolic markers and reduces the progression of disease patterns. Optimal supplementation techniques of probiotics in conjunction with prebiotics and synbiotics in DN benefit glycaemic control, renal function, blood lipid profile, inflammation, and oxidative stress. Future randomized controlled trials supplementing specific probiotics coupled with prebiotics and synbiotics, with larger sample sizes and longer follow-up times, will generate more reliable findings for the impact of probiotic supplementation on DN.

The Role of Selenium Nanoparticles in Addressing Diabetic Complications: A Comprehensive Study.

Diabetes, as an emerging epidemic, has put forward a significant spotlight on the evolving population worldwide grounded upon the remarkable affliction of healthcare along with economical conflict. Various studies suggested that, in modern society, lack of maintenance of a healthy life style leads to the occurrence of diabetes as insulin resistant, later having a damaging effect on the pancreatic ß-cells, suggesting various complications. Furthermore, diabetes management is controversial owing to different opinions based on the prevention of complications. For this purpose, nanostructured materials (NSM) like selenium nanoparticles (SeNPs) have proved their efficiency in the therapeutic management of such serious diseases. This review offers an in- -depth idea regarding the pathophysiology, diagnosis and various conventional therapeutics of type 1 and type 2 diabetes, shedding light on Diabetic Nephropathy (DN), a case study of type 1 diabetes. Moreover, this review provides an exhaustive study by highlighting the economic and healthcare burdens associated with diabetes along with the controversies associated with conventional therapeutic management and the promising role of NSM like selenium nanoparticles (SeNPs), as a novel weapon for encountering such fatal diseases.

PPAR gamma agonistic activity of dillapiole: protective effects against diabetic nephropathy.

Using structural similarity approach we identified dillapiole, a phenylpropanoid, the main component of Piper aduncum L. and Anethum graveolens L. essential oils as potential PPARγ agonist. Molecular docking revealed that dillapiole binds to the active site of PPARγ, similar to pioglitazone binding. In silico ADME studies showed that dillapiole has high water solubility and GI absorption. Dillapiole was also observed to be partial agonist of PPARγ receptors with EC50 of 43.95 µM. In BHK-21 cells cultured under hyperglycaemic conditions, dillapiole administration reduced oxidative stress and prevented decrease in histone H3 acetylation (k9/14) levels. In HFD + STZ induced diabetic mice, dillapiole treatment for 7 days was able to improve renal functions and decrease plasma glucose level to 138.39 ± 12.36 mg/dl along with decreasing total cholesterol (29%), triglycerides (48.8%), LDL (24.7%), and VLDL (65%) levels in serum. These results show that dillapiole is a potential PPARγ-agonist and thus needs to explore further.

Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation.

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this study, we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels. Our results demonstrated that RA significantly alleviated renal tubular epithelial injury, particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes, while attenuating the inflammatory response of macrophages, oxidative stress, and cytotoxicity of natural killer cells. These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage, oxidative stress, and inflammation, offering valuable guidance for the clinical application of RA in the treatment of DN.

Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate renal fibrosis in diabetic nephropathy by targeting Hedgehog/SMO signaling.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. In vitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.

Dysregulation of miR-25-3p in Diabetic Nephropathy and Its Role in Inflammatory Response.

To investigate the expression level of miR-25-3p in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), and its effect on proliferation, apoptosis and inflammatory response of mesangial cells cultured with high glucose. Blood samples of all clinical subjects were collected for RT-qPCR analysis to detect serum miR-25-3p levels. Human mesangial cells (HMCs) cultured with high glucose were used to construct DN model in vitro. MTT assay, flow cytometry and ELISA were used to evaluate the effects of miR-25-3p on the proliferation, apoptosis, and inflammatory response of DN cell models. Serum miR-25-3p was decreased in both T2DM group and DN group, but more in DN group. Serum miR-25-3p was positively correlated with eGFR and negatively correlated with UAER. The expression of miR-25-3p was reduced in HMCs induced by high glucose. Transfection of miR-25-3p mimic could significantly up-regulate the miR-25-3p level in HMCs. Besides, high glucose culture resulted in abnormal proliferation of HMCs, reduced apoptotic cells, and increased inflammation. The addition of miR-25-3p mimic significantly inhibited cell proliferation and promoted cell apoptosis and reduced the production of inflammatory factors. The abnormal reduction of serum miR-25-3p in DN indicates that it may be a potential biomarker for clinical diagnosis of DN. In in vitro experiments, miR-25-3p was involved in the progression of DN by regulating cell proliferation, apoptosis, and inflammatory response.

Understanding the Roles of Non-coding RNAs and Exosomal Non-Coding RNAs in Diabetic Nephropathy.

One of the greatest serious side effects of diabetes is diabetic nephropathy (DN), which is also the key factor in the sometimes-deadly diabetic end-stage renal disease. Progressive renal interstitial fibrosis is closely associated with oxidative stress, and the extracellular matrix is typically a feature of DN. Some RNAs formed by genome transcription that are not translated into proteins are recognized as noncoding RNAs. It has been shown that ncRNAs control apoptosis, inflammatory response, cell proliferation, autophagy, and other pathogenic processes, contributing to the pathogenesis of DN. Exosomes are nano-carriers vesicles that variety in size from 40 to 160 nm. Exosomes are widely present and dispersed in different bodily fluids, plentiful in nucleic acids, lipids, and proteins (microRNA, mRNA, tRNA, lncRNA, circRNA, etc.). Exosomes play a crucial role as messengers for cellular communication. They transport and transmit key signaling molecules, participate in the transfer of information and materials between cells, control cellular physiological processes, and are carefully linked to the beginning and development of many diseases. Herein, we summarized the role of different ncRNAs in DN. Moreover, we highlighted the role of the exosomal form of ncRNAs in the DN pathogenesis.

Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy.

LncRNA XLOC_032768 is reported to prevent renal tubular epithelial cells from cisplatin-induced apoptosis, suggesting its involvement in the development of kidney injury. The present study aimed to explore the role of XLOC_032768 in diabetic nephropathy (DN). The present study enrolled a total of 140 healthy controls (Control group) and 140 patients with type 2 diabetes (Diabetes group). Expression of XLOC_032768 in plasma from these participants was analyzed by performing RT-qPCR. The 140 diabetic patients were followed up for 5 years to monitor the occurrence of diabetic complications. The role of XLOC_032768 in predicting the occurrence of diabetic complications, including DN, diabetic cardiomyopathy (DC), diabetic retinopathy (DR), and diabetic foot (DF) were analyzed by plotting receiver operating characteristic curves and complication-free curves. On the day of admission, plasma levels of XLOC_032768 were not significantly different between Control and Diabetes groups. During follow-up, a total of 22, 15, 13, and 15 cases were diagnosed as DN, DC, DR, and DF, respectively. On the day of diagnosis, plasma levels of XLOC_032768 were only decreased in DN group, but not in other groups, compared to plasma levels of XLOC_032768 on the day of admission. Using plasma levels of XLOC_032768 on the day of admission as a biomarker, potential DN patients were effectively separated from patients with other potential complications and diabetic patients without complications. The 140 diabetic patients were grouped into high and low XLOC_032768 level groups. It was observed that low XLOC_032768 level group showed increased occurrence of DN, but not other complications, compared to high XLOC_032768 level group. Therefore, the downregulation of lncRNA XLOC_032768 in diabetic patients may predict the occurrence of DN.

Ultrasensitive CCL2 Detection in Urine for Diabetic Nephropathy Diagnosis Using a WS2-Based Plasmonic Biosensor.

The accurate diagnosis of diabetic nephropathy relies on achieving ultrasensitive biosensing for biomarker detection. However, existing biosensors face challenges such as poor sensitivity, complexity, time-consuming procedures, and high assay costs. To address these limitations, we report a WS2-based plasmonic biosensor for the ultrasensitive detection of biomarker candidates in clinical human urine samples associated with diabetic nephropathy. Leveraging plasmonic-based electrochemical impedance microscopy (P-EIM) imaging, we observed a remarkable charge sensitivity in monolayer WS2 single crystals. Our biosensor exhibits an exceptionally low detection limit (0.201 ag/mL) and remarkable selectivity in detecting CC chemokine ligand 2 (CCL2) protein biomarkers, outperforming conventional techniques such as ELISA. This work represents a breakthrough in traditional protein sensors, providing a direction and materials foundation for developing ultrasensitive sensors tailored to clinical applications for biomarker sensing.

[Mechanism of traditional Chinese medicine in regulating NLRP3 inflammasomes to alleviate renal interstitial fibrosis in diabetic nephropathy: a review].

Diabetic nephropathy(DN), a progressive chronic kidney disease(CKD) induced by diabetes mellitus, is the main cause of end-stage renal disease. Renal interstitial fibrosis(RIF) is an irreversible factor in the progression and deterioration of the renal function in DN. Chronic inflammation has become a key link in the pathogenesis of DN-RIF. The NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome is an important inflammatory regulator regulated by a variety of signals. It promotes the production of pro-inflammatory cytokines and induces renal inflammatory cell infiltration to participate in the process of renal fibrosis, demonstrating a complex mechanism of action. In view of the important role of NLRP3 inflammasomes in the prevention and treatment of DN-RIF, a large number of experimental studies have demonstrated that traditional Chinese medicine(TCM) can reduce the inflammation by regulating the pathways involving NLRP3 inflammasome, thereby slowing down the progression of DN-RIF and improving the renal function. This paper reviews the relationship between NLRP3 inflammasomes and DN-RIF, and the research progress in the mechanism of TCM intervention in NLRP3 inflammasomes to alleviate DN-RIF, aiming to provide new ideas for the targeted treatment of DN-RIF.

Arsenic aggravates the progression of diabetic nephropathy through miRNA-mRNA-autophagy axis.

Environmental factors play an important role in the progression of diabetic nephropathy (DN), and previous study has shown that arsenic exposure can promote kidney damage in DN rats, however there is no relevant mechanism study so far. In this study, an arsenic-exposed (10 mg/L and 25 mg/L) DN mouse model was established through drinking water for 14 weeks. The results showed that 25 mg/L arsenic exposure increased the renal fibrosis in DN mice significantly, and urinary mAlb level increased with the increasing of arsenic exposure level. Transcriptome sequencing showed that autophagy-related pathways were significantly activated under the exposure dose of 25 mg/L, and levels of Beclin1 and p-ATG16L1/ATG16L1 were significantly higher in the 25 mg/L arsenic group compared to the control group. Silico analysis predicted the microRNAs those could regulate the hub genes of Mapk1, Rhoa and Cdc42, and dual-luciferase gene reporter assay was used to verify the targeted binding between these mRNAs and microRNAs. Our results suggested that high arsenic exposure could aggravate the progression of DN by altering autophagy, the miRNA-mRNA axles of let-7a-1-3p, let-7b-3p, let-7f-1-3p, miR-98-3p/Cdc42, Mapk1, Rhoa, could be considered promising targets to explore the mechanisms and therapeutic measures of DN after exposure to high levels of arsenic.

Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.

Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a secreted proteoglycan, with notable expression in kidney, which attenuates inflammation and albuminuria. However, little is known about Esm1 expression in mature tissues in the presence or absence of diabetes. We utilized publicly available single-cell RNA sequencing data to characterize Esm1 expression in 27,786 renal endothelial cells (RECs) obtained from four human and three mouse databases. We validated our findings using bulk transcriptome data from 20 healthy subjects and 41 patients with DKD and using RNAscope. In both mice and humans, Esm1 is expressed in a subset of all RECs types and represents a minority of glomerular RECs. In patients, Esm1(+) cells exhibit conserved enrichment for blood vessel development genes. With diabetes, these cells are fewer in number and shift expression towards chemotaxis pathways. Esm1 correlates with a majority of genes within these pathways, delineating a glomerular transcriptional polarization reflected by the magnitude of Esm1 deficiency. Diabetes correlates with lower Esm1 expression and with changes in the functional characterization of Esm1(+) cells. Esm1 thus appears as a marker for glomerular transcriptional polarization in DKD.

Chinese herbal medicine for the treatment of diabetic nephropathy: From clinical evidence to potential mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is a typical chronic microvascular complication of diabetes, characterized by proteinuria and a gradual decline in renal function. At present, there are limited clinical interventions aimed at preventing the progression of DN to end-stage renal disease (ESRD). However, Chinese herbal medicine presents a distinct therapeutic approach that can be effectively combined with conventional Western medicine treatments to safeguard renal function. This combination holds considerable practical implications for the treatment of DN. AIM OF THE STUDY: This review covers commonly used Chinese herbal remedies and decoctions applicable to various types of DN, and we summarize the role played by their active ingredients in the treatment of DN and their mechanisms, which includes how they might improve inflammation and metabolic abnormalities to provide new ideas to cope with the development of DN. MATERIALS AND METHODS: With the keywords "diabetic nephropathy," "Chinese herbal medicine," "clinical effectiveness," and "bioactive components," we conducted an extensive literature search of several databases, including PubMed, Web of Science, CNKI, and Wanfang database, to discover studies on herbal formulas that were effective in slowing the progression of DN. The names of the plants covered in the review have been checked at MPNS (http://mpns.kew.org). RESULTS: This review demonstrates the superior total clinical effective rate of combining Chinese herbal medicines with Western medicines over the use of Western medicines alone, as evidenced by summarizing the results of several clinical trials. Furthermore, the review highlights the nephroprotective effects of seven frequently used herbs exerting beneficial effects such as podocyte repair, anti-fibrosis of renal tissues, and regulation of glucose and lipid metabolism through multiple signaling pathways in the treatment of DN. CONCLUSIONS: The potential of herbs in treating DN is evident from their excellent effectiveness and the ability of different herbs to target various symptoms of the condition. However, limitations arise from the deficiencies in interfacing with objective bioindicators, which hinder the integration of herbal therapies into modern medical practice. Further research is warranted to address these limitations and enhance the compatibility of herbal therapies with contemporary medical standards.

Severity of Neuropathy-Related Disability and Associated Factors of Diabetic Peripheral Neuropathy in a Tertiary Healthcare Center: A Comparative Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: The widespread presence of diabetic peripheral neuropathy (DN) and its related variables among diagnosed diabetes mellitus (DM) patients in Kerala lacks sufficient evidence. The objective of this study was to evaluate the frequency of DN and its related risk variables among those with DM who were receiving care at a tertiary health institution in Kerala. MATERIALS AND METHODS: This study was conducted in a tertiary health center in Kerala using a cross-sectional design. The diagnosis of diabetes was established by assessing the glycated hemoglobin A1c (HbA1c) level and the fasting blood glucose (FBG) level. A validated survey questionnaire was employed to gather demographic data as well as the medical history of DM and associated ailments. A thorough physical examination, BMI, and blood pressure were recorded. Dermatological, musculoskeletal, neurological, and vascular assessments were conducted. The subjects were assessed for neuropathy using a neuropathy disability score (NDS). Consequently, those who met the criteria for DM were classified into two groups: those with neuropathy and those without neuropathy. All research participants underwent laboratory examinations such as blood lipid profiles, HbA1c, and vitamin B12 complex concentrations. RESULTS: The study included 200 DM patients; 120 men and 80 women. Study participants were 40-70 years old, with a median age of 53. The prevalence of DN significantly increased with age (p<0.001). The longer a patient had DM, the higher the prevalence of DN, and this variance in percentage was statistically significant (p<0.009) with an OR (odds ratio) of 9.246. A statistically significant 81 (40.5%) of participants graduated, compared to 119 (59.5%) with only higher secondary education or less (OR = 2.042; p = 0.014). Approximately 107 (53.5%) of individuals earned an income under two lakhs, and this disparity was deemed statistically significant (p = 0.003) with an OR of 2.357. In the group of individuals being studied, 53 (26.5%) of them experienced a decrease in pressure sensation, 47 (23.5%) had a decrease or absence of vibration perception, 48 (24%) had an absence or decreased pinprick response, and 46 (23%) had an absent ankle reflex. The study found that the most commonly reported symptoms were tingling (n = 44; 22%), numbness (n = 42; 21%), burning (n = 37; 18.5%), pricking (n = 29; 14.5%), and pain (n = 27; 13.5%). A strong association was found between DN and glycemic status, namely, FBG levels exceeding 140 mg/dL (OR = 4.511, p < 0.001) and HbA1c levels exceeding 6.5% (OR = 3.87, p < 0.001). The prevalence of abnormal vitamin B12 levels in individuals with DN was 63% (p = 0.19), indicating that the finding was not statistically significant. Within the group of individuals with DN being studied, 22% exhibited mild neuropathy, 34% displayed moderate neuropathy, and 44% had severe neuropathy. The DN individuals had significantly reduced ankle dorsiflexion in cases of severe NDS scores compared to those with mild to moderate NDS scores (p = 0.009). During the binary logistic regression analysis, it was shown that the duration of DM (OR = 1.73; p = 0.038) and FBG levels (OR = 2.87; p = 0.018) were determined as predictors for DN. CONCLUSION: The findings of this study reveal that the duration of diabetes, age, literacy level, income, HbA1c, and FBG were substantially related to a higher likelihood of DN among diabetic patients.

Effect of miR-1297 on Kidney Injury in Rats with Diabetic Nephropathy through the PTEN/PI3K/AKT Pathway.

PURPOSE: This study aimed to determine the influence of miR-1297 on kidney injury in rats with diabetic nephropathy (DN) and its causal role. METHODS: A DN rat model was established through right kidney resection and intraperitoneal injection of streptozotocin (STZ). Sham rats did not undergo right kidney resection or STZ injection. The DN rats were divided into the DN model and antagomiR-1297 treatment groups. Kidney morphology was observed using hematoxylin and eosin staining. Renal function indices, including blood urea nitrogen (BUN), serum creatinine (SCr), and urinary protein, were measured using kits. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were determined through enzyme-linked immunosorbent assay (ELISA). Fibrin (FN), collagen type I (Col I), and α-smooth muscle actin (α-SMA) were assessed through western blotting and real-time reverse transcription-polymerase chain reaction. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. miR-1297 targets were predicted using bioinformatic software and verified through luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway expression was analyzed through western blotting. RESULTS: AntagomiR-1297 reduced BUN (p = 0.005), SCr (p = 0.012), and urine protein (p < 0.001) levels and improved kidney tissue morphology. It prevented renal interstitial fibrosis by decreasing FN, Col I, and α-SMA protein levels (all p < 0.001). AntagomiR-1297 increased SOD (p = 0.001) and GSH-Px (p = 0.002) levels. Additionally, it reduced levels of cell inflammatory factors, including TNF-α, IL-6, and IL-1ß (all p < 0.001), and alleviated apoptosis (p < 0.001) in rat kidney tissue with DN. miR-1297 was pinpointed as a target for PTEN. AntagomiR-1297 increased PTEN expression and suppressed PI3K and AKT phosphorylation (all p < 0.001). CONCLUSIONS: AntagomiR-1297 can mitigate renal fibrosis, renal inflammation, apoptosis, and oxidative stress levels through the PTEN/PI3K/AKT pathway.

Depression of LncRNA DANCR alleviates tubular injury in diabetic nephropathy by regulating KLF5 through sponge miR-214-5p.

OBJECTIVE: Diabetic nephropathy (DN) manifests a critical aspect in the form of renal tubular injury. The current research aimed to determine the function and mechanism of long non-coding ribonucleic acid (LncRNA) differentiation antagonising non-protein coding RNA (DANCR), with a focus on its impact on renal tubular injury. METHODS: Quantitative reverse transcription polymerase chain reaction was employed to analyze the RNA levels of DANCR in the serum of patients with DN or human proximal tubular epithelial cells (human kidney 2 [HK2]). The diagnostic significance of DANCR was assessed using a receiver operating characteristic curve. A DN model was established by inducing HK-2 cells with high glucose (HG). Cell proliferation, apoptosis, and the levels of inflammatory factors, reactive oxygen species (ROS), and malondialdehyde (MDA) were detected using the Cell Counting Kit - 8, flow cytometry, and enzyme-linked immunosorbent assay. The interaction between microRNA (miR)-214-5p and DANCR or Krüppel-like factor 5 (KLF5) was investigated using RNA immunoprecipitation and dual-luciferase reporter assays. RESULTS: Elevated levels of DANCR were observed in the serum of patients with DN and HG-inducted HK-2 cells (P < 0.05). DANCR levels effectively identified patients with DN from patients with type 2 diabetes mellitus. Silencing of DANCR protected against HG-induced tubular injury by restoring cell proliferation, inhibiting apoptosis, and reducing the secretion of inflammatory factors and oxidative stress production (P < 0.05). DANCR functions as a sponge for miR-214-5p, and the mitigation of DANCR silencing on HG-induced renal tubular injury was partially attenuated with reduced miR-214-5p (P < 0.05). Additionally, KLF5 was identified as the target of miR-214-5p. CONCLUSION: DANCR was identified as diagnostic potential for DN and the alleviation of renal tubular injury via the miR-214-5p/KLF5 axis, following DANCR silencing, introduces a novel perspective and approach to mitigating DN.

Exercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism.

Diabetic nephropathy (DN) is a serious complication of diabetes, and its progression is influenced by factors like oxidative stress, inflammation, cell death, and fibrosis. Compared to drug treatment, exercise offers a cost-effective and low-risk approach to slowing down DN progression. Through multiple ways and mechanisms, exercise helps to control blood sugar and blood pressure and reduce serum creatinine and albuminuria, thereby alleviating kidney damage. This review explores the beneficial effects of exercise on DN improvement and highlights its potential mechanisms for ameliorating DN. In-depth understanding of the role and mechanism of exercise in improving DN would pave the way for formulating safe and effective exercise programs for the treatment and prevention of DN.

Navigating the future of diabetes: innovative nomogram models for predicting all-cause mortality risk in diabetic nephropathy.

OBJECTIVE: This study aims to establish and validate a nomogram model for the all-cause mortality rate in patients with diabetic nephropathy (DN). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. A random split of 7:3 was performed between the training and validation sets. Utilizing follow-up data until December 31, 2019, we examined the all-cause mortality rate. Cox regression models and Least Absolute Shrinkage and Selection Operator (LASSO) regression models were employed in the training cohort to develop a nomogram for predicting all-cause mortality in the studied population. Finally, various validation methods were employed to assess the predictive performance of the nomogram, and Decision Curve Analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. RESULTS: After the results of LASSO regression models and Cox multivariate analyses, a total of 8 variables were selected, gender, age, poverty income ratio, heart failure, body mass index, albumin, blood urea nitrogen and serum uric acid. A nomogram model was built based on these predictors. The C-index values in training cohort of 3-year, 5-year, 10-year mortality rates were 0.820, 0.807, and 0.798. In the validation cohort, the C-index values of 3-year, 5-year, 10-year mortality rates were 0.773, 0.788, and 0.817, respectively. The calibration curve demonstrates satisfactory consistency between the two cohorts. CONCLUSION: The newly developed nomogram proves to be effective in predicting the all-cause mortality risk in patients with diabetic nephropathy, and it has undergone robust internal validation.

Analysis of clinical evidence on traditional Chinese medicine for the treatment of diabetic nephropathy: a comprehensive review with evidence mapping.

Objective: This study aims to map evidence from Randomized Controlled Trials (RCTs) and systematic reviews/Meta-analyses concerning the treatment of Diabetic Nephropathy (DN) with Traditional Chinese Medicine (TCM), understand the distribution of evidence in this field, and summarize the efficacy and existing problems of TCM in treating DN. The intention is to provide evidence-based data for TCM in preventing and treating DN and to offer a reference for defining future research directions. Methods: Comprehensive searches of major databases were performed, spanning from January 2016 to May 2023, to include clinical RCTs and systematic reviews/Meta-analyses of TCM in treating DN. The analysis encompasses the publishing trend of clinical studies, the staging of research subjects, TCM syndrome differentiation, study scale, intervention plans, and outcome indicators. Methodological quality of systematic reviews was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) checklist, and evidence distribution characteristics were analyzed using a combination of text and charts. Results: A total of 1926 RCTs and 110 systematic reviews/Meta-analyses were included. The majority of studies focused on stage III DN, with Qi-Yin deficiency being the predominant syndrome type, and sample sizes most commonly ranging from 60 to 100. The TCM intervention durations were primarily between 12-24 weeks. Therapeutic measures mainly consisted of Chinese herbal decoctions and patented Chinese medicines, with a substantial focus on clinical efficacy rate, TCM symptomatology, and renal function indicators, while attention to quality of life, dosage of Western medicine, and disease progression was inadequate. Systematic reviews mostly scored between 5 and 8 on the AMSTAR scale, and evidence from 94 studies indicated potential positive effects. Conclusion: DN represents a significant health challenge, particularly for the elderly, with TCM showing promise in symptom alleviation and renal protection. Yet, the field is marred by research inconsistencies and methodological shortcomings. Future investigations should prioritize the development of standardized outcome sets tailored to DN, carefully select evaluation indicators that reflect TCM's unique intervention strategies, and aim to improve the robustness of clinical evidence. Emphasizing TCM's foundational theories while incorporating advanced scientific technologies will be essential for innovating research methodologies and uncovering the mechanisms underlying TCM's efficacy in DN management.

Association between gut microbiota and diabetic nephropathy: a mendelian randomization study.

Background: The correlation between diabetic nephropathy (DN) and gut microbiota (GM) has been suggested in numerous animal experiments and cross-sectional studies. However, a causal association between GM and DN has not been ascertained. Methods: This research adopted MR analysis to evaluate the causal link between GM and DN derived from data acquired through publicly available genome-wide association studies (GWAS). The study utilized the inverse variance weighted (IVW) approach to assess causal association between GM and DN. Four additional methods including MR-Egger, weighted median, weighted mode, and simple mode were employed to ensure comprehensive analysis and robust results. The Cochran's Q test and the MR-Egger method were conducted to identify heterogeneity and horizontal pleiotropy, respectively. The leave-one-out approach was utilized to evaluate the stability of MR results. Finally, a reverse MR was performed to identify the reverse causal association between GM and DN. Results: According to IVW analysis, Class Verrucomicrobiae (p = 0.003), Order Verrucomicrobiales (p = 0.003), Family Verrucomicrobiaceae (p = 0.003), Genus Akkermansia (p = 0.003), Genus Catenibacterium (p = 0.031), Genus Coprococcus 1 (p = 0.022), Genus Eubacterium hallii group (p = 0.018), and Genus Marvinbryantia (p = 0.023) were associated with a higher risk of DN. On the contrary, Class Actinobacteria (p = 0.037), Group Eubacterium ventriosum group (p = 0.030), Group Ruminococcus gauvreauii group (p = 0.048), Order Lactobacillales (p = 0.045), Phylum Proteobacteria (p = 0.017) were associated with a lower risk of DN. The sensitivity analysis did not identify any substantial pleiotropy or heterogeneity in the outcomes. We found causal effects of DN on 11 GM species in the reverse MR analysis. Notably, Phylum Proteobacteria and DN are mutually causalities. Conclusion: This study identified the causal association between GM and DN with MR analysis, which may enhance the understanding of the intestinal-renal axis and provide novel potential targets for early non-invasive diagnosis and treatment of DN.