cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29039723
title: The m6A reader YTHDF2 protects vascular smooth muscle cells against the osteogenic differentiation through targeting Runx2

description: Vascular calcification (VC) is an important pathological development progress in chronic kidney disease (CKD) and may increase mortality but lacks effective treatments. N6-methyladenosine (m6A) has been verified to be the most prevalent internal chemical RNA modification in mammalian mRNAs. The M6A-modified mRNA degradation process is mediated by the reader YTHDF2 in an m6A-dependent manner. Nevertheless, the exact role and molecular mechanism of YTHDF2 in VC remain unclear. This study aimed to investigate the potential role of YTHDF2 in the osteogenic differentiation of vascular smooth muscle cells (VSMCs). It was found that YTHDF2 was markedly downregulated in both <i>in vivo</i> and <i>in vitro</i> calcified models. Functionally, YTHDF2 plays a protective role in VC. The overexpression of YTHDF2 inhibited the transdifferentiation of VSMCs from a contractile to an osteogenic phenotype, thus decreasing the expression of mineralization regulatory proteins and calcium deposition. Conversely, YTHDF2 deficiency aggravated this process. At the mechanistic level, YTHDF2 suppressed osteogenic transdifferentiation of VSMCs by regulating the Runt-related transcription factor 2 (Runx2). RNA immunoprecipitation-qPCR (RIP-qPCR) confirmed the binding of YTHDF2 to Runx2, and luciferase reporter assays confirmed the presence of the m6A site in Runx2. In addition, an actinomycin D assay showed that the half-life of Runx2 mRNA was dramatically shortened in VSMCs overexpressing YTHDF2. These results suggest that YTHDF2 directly binds to the m6A modification site of Runx2 to mediate the mRNA degradation that prevents VC by inhibiting the osteogenic development of VSMCs. Therefore, YTHDF2 can be considered a potential therapeutic target for managing VC.
DOI: 10.6084/m9.figshare.29039723.v1
title: The m6A reader YTHDF2 protects vascular smooth muscle cells against the osteogenic differentiation through targeting Runx2

description: Vascular calcification (VC) is an important pathological development progress in chronic kidney disease (CKD) and may increase mortality but lacks effective treatments. N6-methyladenosine (m6A) has been verified to be the most prevalent internal chemical RNA modification in mammalian mRNAs. The M6A-modified mRNA degradation process is mediated by the reader YTHDF2 in an m6A-dependent manner. Nevertheless, the exact role and molecular mechanism of YTHDF2 in VC remain unclear. This study aimed to investigate the potential role of YTHDF2 in the osteogenic differentiation of vascular smooth muscle cells (VSMCs). It was found that YTHDF2 was markedly downregulated in both <i>in vivo</i> and <i>in vitro</i> calcified models. Functionally, YTHDF2 plays a protective role in VC. The overexpression of YTHDF2 inhibited the transdifferentiation of VSMCs from a contractile to an osteogenic phenotype, thus decreasing the expression of mineralization regulatory proteins and calcium deposition. Conversely, YTHDF2 deficiency aggravated this process. At the mechanistic level, YTHDF2 suppressed osteogenic transdifferentiation of VSMCs by regulating the Runt-related transcription factor 2 (Runx2). RNA immunoprecipitation-qPCR (RIP-qPCR) confirmed the binding of YTHDF2 to Runx2, and luciferase reporter assays confirmed the presence of the m6A site in Runx2. In addition, an actinomycin D assay showed that the half-life of Runx2 mRNA was dramatically shortened in VSMCs overexpressing YTHDF2. These results suggest that YTHDF2 directly binds to the m6A modification site of Runx2 to mediate the mRNA degradation that prevents VC by inhibiting the osteogenic development of VSMCs. Therefore, YTHDF2 can be considered a potential therapeutic target for managing VC.
DOI: 10.6084/m9.figshare.28467584
title: Integrative analysis of mitochondrial and immune pathways in diabetic kidney disease: identification of AASS and CASP3 as key predictors and therapeutic targets

description: Diabetic kidney disease (DKD) is driven by mitochondrial dysfunction and immune dysregulation, yet the mechanistic interplay remains poorly defined. This study aimed to identify key molecular networks linking mitochondrial and immune pathways to DKD progression, with a focus on uncovering biomarkers and therapeutic targets. We conducted an integrative analysis of human DKD cohorts (GSE30122, GSE96804) using weighted gene co-expression network analysis (WGCNA) to identify gene modules enriched for immune response genes and mitochondrial pathways (from MitoCarta3.0). Machine learning algorithms were employed to prioritize key biomarkers for further investigation. Experimental validation was performed using a DKD rat model. WGCNA revealed significant gene modules associated with immune responses and mitochondrial functions. Machine learning analysis highlighted two central biomarkers: aminoadipate-semialdehyde synthase (AASS) and caspase-3 (CASP3). In the DKD rat model, elevated levels of AASS and CASP3 were found to correlate with increased oxidative stress. Mechanistically, AASS was shown to drive mitochondrial damage via lysine metabolism, while CASP3 amplified inflammatory apoptosis pathways. Our findings establish AASS and CASP3 as dual biomarkers and therapeutic targets, bridging mitochondrial-immune crosstalk to DKD pathogenesis. This multi-omics framework provides actionable insights for targeting kidney damage in diabetes.
DOI: 10.6084/m9.figshare.28467584.v1
title: Integrative analysis of mitochondrial and immune pathways in diabetic kidney disease: identification of AASS and CASP3 as key predictors and therapeutic targets

description: Diabetic kidney disease (DKD) is driven by mitochondrial dysfunction and immune dysregulation, yet the mechanistic interplay remains poorly defined. This study aimed to identify key molecular networks linking mitochondrial and immune pathways to DKD progression, with a focus on uncovering biomarkers and therapeutic targets. We conducted an integrative analysis of human DKD cohorts (GSE30122, GSE96804) using weighted gene co-expression network analysis (WGCNA) to identify gene modules enriched for immune response genes and mitochondrial pathways (from MitoCarta3.0). Machine learning algorithms were employed to prioritize key biomarkers for further investigation. Experimental validation was performed using a DKD rat model. WGCNA revealed significant gene modules associated with immune responses and mitochondrial functions. Machine learning analysis highlighted two central biomarkers: aminoadipate-semialdehyde synthase (AASS) and caspase-3 (CASP3). In the DKD rat model, elevated levels of AASS and CASP3 were found to correlate with increased oxidative stress. Mechanistically, AASS was shown to drive mitochondrial damage via lysine metabolism, while CASP3 amplified inflammatory apoptosis pathways. Our findings establish AASS and CASP3 as dual biomarkers and therapeutic targets, bridging mitochondrial-immune crosstalk to DKD pathogenesis. This multi-omics framework provides actionable insights for targeting kidney damage in diabetes.
DOI: 10.6084/m9.figshare.29039726
title: Sodium aescinate protects renal ischemia-reperfusion and pyroptosis through AKT/NLRP3 signaling pathway

description: Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal injury. Studies have shown that sodium aescinate (SA) may serve as a potential therapeutic agent, although its exact mechanism remains unclear. This study first evaluated the efficacy of SA using a mouse renal ischemia-reperfusion model. Subsequently, its mechanism was elucidated through systematic bioinformatics, and finally validated through <i>in vitro</i> and <i>in vivo</i> experiments. The results demonstrated that SA has a protective effect on renal function in mice with RIRI. Bioinformatic analysis indicated that the pyroptosis pathway is significantly activated during renal ischemia-reperfusion injury, and immunohistochemistry showed that the level of renal pyroptosis is upregulated during ischemia-reperfusion injury. Administration of SA was able to reduce the expression of pyroptosis-related proteins (GSDMD, NLRP3, IL-1β) in RIRI. <i>In vitro</i> and <i>in vivo</i> experiments further confirmed that SA exerts an anti-pyroptotic effect by inhibiting the AKT/NLRP3 signaling pathway. Ultimately, SA mitigates kidney injury in IRI mice by suppressing renal failure through inhibition of the AKT/NLRP3 signaling pathway.
DOI: 10.6084/m9.figshare.29039726.v1
title: Sodium aescinate protects renal ischemia-reperfusion and pyroptosis through AKT/NLRP3 signaling pathway

description: Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal injury. Studies have shown that sodium aescinate (SA) may serve as a potential therapeutic agent, although its exact mechanism remains unclear. This study first evaluated the efficacy of SA using a mouse renal ischemia-reperfusion model. Subsequently, its mechanism was elucidated through systematic bioinformatics, and finally validated through <i>in vitro</i> and <i>in vivo</i> experiments. The results demonstrated that SA has a protective effect on renal function in mice with RIRI. Bioinformatic analysis indicated that the pyroptosis pathway is significantly activated during renal ischemia-reperfusion injury, and immunohistochemistry showed that the level of renal pyroptosis is upregulated during ischemia-reperfusion injury. Administration of SA was able to reduce the expression of pyroptosis-related proteins (GSDMD, NLRP3, IL-1β) in RIRI. <i>In vitro</i> and <i>in vivo</i> experiments further confirmed that SA exerts an anti-pyroptotic effect by inhibiting the AKT/NLRP3 signaling pathway. Ultimately, SA mitigates kidney injury in IRI mice by suppressing renal failure through inhibition of the AKT/NLRP3 signaling pathway.
DOI: 10.6084/m9.figshare.28954405
title: The prognostic value of the neutrophil-percentage-to-albumin ratio for all-cause and cardiovascular mortality in chronic kidney disease stages G3a to G5: insights from NHANES 2003–2018

description: Patients with chronic kidney disease (CKD) stages G3a to G5 frequently experience heightened systemic inflammation and nutritional loss. Identifying laboratory-accessible, cost-effective markers that can effectively predict the prognosis of CKD stages G3a to G5 is crucial. This prospective cohort study included 3,331 patients with CKD stages G3a to G5 who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Multivariable adjusted Cox proportional hazards regression models and restricted cubic spline analyses were used to assess the associations of neutrophil percentage-to-albumin ratio (NPAR) levels with all-cause mortality, CVD, and non-CVD mortality. The cohort study encompassed data from 3,331 participants for analysis. Nonlinear J-shaped associations were observed between NPAR levels and the risk of all-cause, CVD, and non-CVD mortality in patients with CKD stages G3a to G5. High levels NPAR exhibited a significantly elevated risk of both all-cause and CVD mortality in the fully adjusted model. The respective hazard ratios (HRs) for all-cause mortality were 1.23 [95% confidence interval (CI), 1.05–1.44], and for CVD mortality, 1.513 (95% CI, 1.131–2.024). Elevated NPAR can predict both all-cause and CVD deaths in advanced CKD patients. Individuals with high NPAR levels face an elevated risk of mortality and exhibit a decreased survival rate in the context of CKD. This finding offers evidence supporting the timely evaluation and intervention for inflammation and nutritional status in individuals with CKD stages G3a to G5.
DOI: 10.6084/m9.figshare.28954405.v1
title: The prognostic value of the neutrophil-percentage-to-albumin ratio for all-cause and cardiovascular mortality in chronic kidney disease stages G3a to G5: insights from NHANES 2003–2018

description: Patients with chronic kidney disease (CKD) stages G3a to G5 frequently experience heightened systemic inflammation and nutritional loss. Identifying laboratory-accessible, cost-effective markers that can effectively predict the prognosis of CKD stages G3a to G5 is crucial. This prospective cohort study included 3,331 patients with CKD stages G3a to G5 who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Multivariable adjusted Cox proportional hazards regression models and restricted cubic spline analyses were used to assess the associations of neutrophil percentage-to-albumin ratio (NPAR) levels with all-cause mortality, CVD, and non-CVD mortality. The cohort study encompassed data from 3,331 participants for analysis. Nonlinear J-shaped associations were observed between NPAR levels and the risk of all-cause, CVD, and non-CVD mortality in patients with CKD stages G3a to G5. High levels NPAR exhibited a significantly elevated risk of both all-cause and CVD mortality in the fully adjusted model. The respective hazard ratios (HRs) for all-cause mortality were 1.23 [95% confidence interval (CI), 1.05–1.44], and for CVD mortality, 1.513 (95% CI, 1.131–2.024). Elevated NPAR can predict both all-cause and CVD deaths in advanced CKD patients. Individuals with high NPAR levels face an elevated risk of mortality and exhibit a decreased survival rate in the context of CKD. This finding offers evidence supporting the timely evaluation and intervention for inflammation and nutritional status in individuals with CKD stages G3a to G5.
DOI: 10.6084/m9.figshare.29039732
title: The impact of rising peripheral blood naïve CD8<sup>+</sup> T cell levels on chronic kidney disease onset: a Mendelian randomization study

description: The global incidence of chronic kidney disease (CKD) is rising rapidly. Immune cells play a crucial role in the onset and progression of CKD, however, the causal relationships and underlying immunological mechanisms remain incompletely elucidated. This deficiency hinders the development and application of early interventions and immunotherapies for CKD. In this study, we hypothesize that alterations in immune cell phenotypes (ICPs) in the blood may influence the onset of CKD. We collated Genome Wide Association Studies (GWAS) data for 731 ICPs, alongside summary data for CKD and estimated glomerular filtration rate (eGFR). Utilizing bidirectional mendelian randomization analysis (MR), we identified the impact of ICPs on the onset of CKD. Preliminary MR analyses revealed three ICPs positively associated with CKD onset: the absolute number of CD45RA<sup>+</sup> CD28<sup>−</sup> CD8<sup>+</sup> T cells (<i>p</i> = 1.209 × 10<sup>−15</sup>, 95% CI: 1.0002–1.0003), the percentage of CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>+</sup> T cells of total T cells (<i>p</i> = 5.831 × 10<sup>−6</sup>, 95% CI: 1.0028–1.0070), and the percentage of CD45RA<sup>−</sup> CD28<sup>−</sup> CD8<sup>+</sup> T cells of total T cells (<i>p</i> = 4.292 × 10<sup>−5</sup>, 95% CI: 1.0005–1.0015). After conducting sensitivity and reverse MR analyses, only the percentage of CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>+</sup> T cells (naïve CD8<sup>+</sup> T Cells) was found to have a sufficiently robust causal impact on CKD. We are the first to demonstrate a significant positive association between the percentage of naïve CD8<sup>+</sup> T cells and CKD onset. This finding offers new insights for early prevention and treatment of CKD.
DOI: 10.6084/m9.figshare.29039732.v1
title: The impact of rising peripheral blood naïve CD8<sup>+</sup> T cell levels on chronic kidney disease onset: a Mendelian randomization study

description: The global incidence of chronic kidney disease (CKD) is rising rapidly. Immune cells play a crucial role in the onset and progression of CKD, however, the causal relationships and underlying immunological mechanisms remain incompletely elucidated. This deficiency hinders the development and application of early interventions and immunotherapies for CKD. In this study, we hypothesize that alterations in immune cell phenotypes (ICPs) in the blood may influence the onset of CKD. We collated Genome Wide Association Studies (GWAS) data for 731 ICPs, alongside summary data for CKD and estimated glomerular filtration rate (eGFR). Utilizing bidirectional mendelian randomization analysis (MR), we identified the impact of ICPs on the onset of CKD. Preliminary MR analyses revealed three ICPs positively associated with CKD onset: the absolute number of CD45RA<sup>+</sup> CD28<sup>−</sup> CD8<sup>+</sup> T cells (<i>p</i> = 1.209 × 10<sup>−15</sup>, 95% CI: 1.0002–1.0003), the percentage of CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>+</sup> T cells of total T cells (<i>p</i> = 5.831 × 10<sup>−6</sup>, 95% CI: 1.0028–1.0070), and the percentage of CD45RA<sup>−</sup> CD28<sup>−</sup> CD8<sup>+</sup> T cells of total T cells (<i>p</i> = 4.292 × 10<sup>−5</sup>, 95% CI: 1.0005–1.0015). After conducting sensitivity and reverse MR analyses, only the percentage of CD28<sup>+</sup> CD45RA<sup>+</sup> CD8<sup>+</sup> T cells (naïve CD8<sup>+</sup> T Cells) was found to have a sufficiently robust causal impact on CKD. We are the first to demonstrate a significant positive association between the percentage of naïve CD8<sup>+</sup> T cells and CKD onset. This finding offers new insights for early prevention and treatment of CKD.
DOI: 10.6084/m9.figshare.28748338
title: Risk prediction for acute kidney disease and adverse outcomes in patients with chronic obstructive pulmonary disease: an interpretable machine learning approach

description: Little is known about acute kidney injury (AKI) and acute kidney disease (AKD) in patients with chronic obstructive pulmonary disease (COPD) and COPD mortality based on the acute/subacute renal injury. This study develops machine learning models to predict AKI, AKD, and mortality in COPD patients, utilizing web applications for clinical decisions. We included 2,829 inpatients from January 2016 to December 2018. Data were split into 80% for training and 20% for testing. Eight machine learning algorithms were used, and model performance was evaluated using various metrics. SHAP was used to visualize the decision process. The best models, assessed using AUROC were used to develop web applications for identifying high-risk patients. The incidence rates were 13.71% for AKI and 15.11% for AKD. The overall mortality rate was 4.84%. LightGBM performed best with AUROC of 0.815, 0.827, and 0.934 in AKI, AKD, and mortality, respectively. Key predictors for AKI were Scr, neutrophil percentage, cystatin c, BUN, and LDH. For AKD, the key predictors were age, AKI grade, HDL-C, Scr, and BUN. The key predictors for mortality included the use of dopamine and epinephrine drugs, cystatin c, renal function trajectory, albumin, and neutrophil percentage. Force plots visualized the prediction process for individual patients. The incidence of AKI and AKD is significant in patients with COPD. Renal function trajectory is crucial for predicting mortality in these patients. Web applications were developed to predict AKI, AKD, and mortality, improving prognosis by identifying high-risk patients and reducing adverse events and disease progression.
DOI: 10.6084/m9.figshare.28748338.v1
title: Risk prediction for acute kidney disease and adverse outcomes in patients with chronic obstructive pulmonary disease: an interpretable machine learning approach

description: Little is known about acute kidney injury (AKI) and acute kidney disease (AKD) in patients with chronic obstructive pulmonary disease (COPD) and COPD mortality based on the acute/subacute renal injury. This study develops machine learning models to predict AKI, AKD, and mortality in COPD patients, utilizing web applications for clinical decisions. We included 2,829 inpatients from January 2016 to December 2018. Data were split into 80% for training and 20% for testing. Eight machine learning algorithms were used, and model performance was evaluated using various metrics. SHAP was used to visualize the decision process. The best models, assessed using AUROC were used to develop web applications for identifying high-risk patients. The incidence rates were 13.71% for AKI and 15.11% for AKD. The overall mortality rate was 4.84%. LightGBM performed best with AUROC of 0.815, 0.827, and 0.934 in AKI, AKD, and mortality, respectively. Key predictors for AKI were Scr, neutrophil percentage, cystatin c, BUN, and LDH. For AKD, the key predictors were age, AKI grade, HDL-C, Scr, and BUN. The key predictors for mortality included the use of dopamine and epinephrine drugs, cystatin c, renal function trajectory, albumin, and neutrophil percentage. Force plots visualized the prediction process for individual patients. The incidence of AKI and AKD is significant in patients with COPD. Renal function trajectory is crucial for predicting mortality in these patients. Web applications were developed to predict AKI, AKD, and mortality, improving prognosis by identifying high-risk patients and reducing adverse events and disease progression.
DOI: 10.6084/m9.figshare.29039735.v1
title: Autosomal dominant polycystic kidney disease: an overview of recent genetic and clinical advances

description: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease, characterized by the progressive development of multiple kidney cysts, leading to a gradual decline in kidney function. ADPKD is also the fourth leading cause of kidney failure (KF) in adults. In addition to kidney manifestations, ADPKD is associated with various extrarenal features, including liver cysts, cardiovascular abnormalities, intracranial aneurysms, and chronic pain with significant impact on patients’ quality of life. While several disease-modifying agents have been tested in ADPKD, tolvaptan remains the only approved drug by the US Food and Drug Administration. The Mayo Imaging Classification is currently the most practical tool for predicting rate of kidney disease progression in ADPKD. This review provides a comprehensive overview of ADPKD, focusing on its genetics, pathophysiology, clinical presentation, management, and prognostic tools. Advances in diagnostic imaging and genetic testing have improved the early detection of ADPKD, allowing better classification of patients and prediction of KF. The review also discusses current therapeutic approaches to ADPKD, including tolvaptan, a vasopressin V2-receptor antagonist. Additionally, we address specific issues in children and pregnant individuals with ADPKD. Despite substantial progress in understanding ADPKD, there is a large need for additional effective treatments and prognostic markers to provide a more personalized care for these patients.