cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28428412.v1
title: Integration of transcriptome and Mendelian randomization analyses in exploring the extracellular vesicle-related biomarkers of diabetic kidney disease

description: Diabetic Kidney Disease (DKD) is a common complication in patients with diabetes, and its pathogenesis remains incompletely understood. Recent studies have suggested that extracellular vesicles (EVs) may play a significant role in the initiation and progression of DKD. This study aimed to identify biomarkers associated with EVs in DKD through bioinformatics and Mendelian randomization (MR) analysis. This study utilized two DKD-related datasets, GSE96804 and GSE30528, alongside 121 exosome-related genes (ERGs) and 200 inflammation-related genes (IRGs). Differential analysis, co-expression network construction, and MR analysis were conducted to identify candidate genes. Machine learning techniques and expression validation were then employed to determine biomarkers. Finally, the potential mechanisms of action of these biomarkers were explored through Immunohistochemistry (IHC) staining, enrichment analysis, immune infiltration analysis, and regulatory network construction. A total of 22 candidate genes were identified as causally linked to DKD. CMAS and RGS10 were identified as biomarkers, with both showing reduced expression in DKD. IHC confirmed low RGS10 expression, providing new insights into DKD management. CMAS was involved primarily in mitochondria-related pathways, while RGS10 was enriched in the extracellular matrix and associated pathways. Significant differences were observed in neutrophils and M2 macrophages between DKD and normal groups, correlating strongly with the biomarkers. This study identified two EV-associated biomarkers, CMAS and RGS10, linked to DKD and elucidated their potential roles in disease progression. These results offer valuable insights for further exploration of DKD pathogenesis and the development of new therapeutic targets.
DOI: 10.6084/m9.figshare.28621039
title: Determining IFI44 as a key lupus nephritis’s biomarker through bioinformatics and immunohistochemistry

description: Lupus nephritis (LN) emerges as a severe complication of systemic lupus erythematosus (SLE), significantly affecting patient survival. Despite improvements in treatment reducing LN’s morbidity and mortality, existing therapies remain suboptimal, emphasizing the necessity for early detection to improve patient outcomes. This study employs bioinformatics and machine learning to identify and validate potential LN biomarkers using immunohistochemistry (IHC). It explores the relationship between these biomarkers and the clinical and pathological characteristics of LN, assessing their prognostic significance. The research provides deeper mechanistic insights by employing Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the study characterizes the immune profiles of LN patients through the CIBERSORT algorithm, focusing on the role of interferon-inducible protein 44 (IFI44) as a key biomarker. IFI44 shows elevated expression in LN-affected kidneys, compared to healthy controls. The levels of IFI44 positively correlate with serum creatinine and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and inversely with serum complement C3 and initial estimated glomerular filtration rate (eGFR). IFI44 is identified as a promising biomarker for LN, offering potential to refine the assessment of disease progression and predict clinical outcomes. This facilitates the development of more personalized treatment strategies for LN patients.
DOI: 10.6084/m9.figshare.28621039.v1
title: Determining IFI44 as a key lupus nephritis’s biomarker through bioinformatics and immunohistochemistry

description: Lupus nephritis (LN) emerges as a severe complication of systemic lupus erythematosus (SLE), significantly affecting patient survival. Despite improvements in treatment reducing LN’s morbidity and mortality, existing therapies remain suboptimal, emphasizing the necessity for early detection to improve patient outcomes. This study employs bioinformatics and machine learning to identify and validate potential LN biomarkers using immunohistochemistry (IHC). It explores the relationship between these biomarkers and the clinical and pathological characteristics of LN, assessing their prognostic significance. The research provides deeper mechanistic insights by employing Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the study characterizes the immune profiles of LN patients through the CIBERSORT algorithm, focusing on the role of interferon-inducible protein 44 (IFI44) as a key biomarker. IFI44 shows elevated expression in LN-affected kidneys, compared to healthy controls. The levels of IFI44 positively correlate with serum creatinine and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and inversely with serum complement C3 and initial estimated glomerular filtration rate (eGFR). IFI44 is identified as a promising biomarker for LN, offering potential to refine the assessment of disease progression and predict clinical outcomes. This facilitates the development of more personalized treatment strategies for LN patients.
DOI: 10.6084/m9.figshare.28551523
title: S-nitrosoglutathione inhibits pyroptosis of kidney tubular epithelial cells in sepsis via the SIRT3/SOD2/mtROS signaling pathway

description: Pyroptosis is considered to play an important role in the occurrence, development and prognosis of septic acute kidney injury (SAKI). We aimed to explore the specific molecular mechanism of S-nitrosoglutathione (SNG) regulating pyroptosis of kidney tubular epithelial cells (KTECs). By constructing a mice model of sepsis, we pretreated them with SNG and used biochemical methods to detect the levels of serum inflammatory factors and mitochondrial reactive oxygen species (mtROS), assessed the severity of kidney injury and KTECs mitochondrial damage, and detected the expression of KTECs pyroptosis-related proteins and sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway proteins. The kidney injury caused by sepsis was significantly aggravated, and the levels of IL-1β, IL-6, IL-18, TNF-α, malondialdehyde (MDA) and mtROS were all increased, accompanied by the decrease of SIRT3 and SOD2 proteins, while NOD-like receptor with pyrin domain 3 (NLRP3), gasdermin D (GSDMD), Caspase-1 proteins expression and the number of KTECs apoptotic cells were all increased. However, after SNG pretreatment, the levels of IL-1β, IL-6, IL-18, TNF-α, MDA and mtROS were all significantly decreased, the expression of SIRT3 and SOD2 proteins were increased, NLRP3, GSDMD, Caspase-1 proteins expression and the number of KTECs apoptotic cells were decreased. SNG protects SAKI by regulating the SIRT3/SOD2/mtROS signaling pathway to inhibit the pyroptosis of KTECs.
DOI: 10.6084/m9.figshare.28551523.v1
title: S-nitrosoglutathione inhibits pyroptosis of kidney tubular epithelial cells in sepsis via the SIRT3/SOD2/mtROS signaling pathway

description: Pyroptosis is considered to play an important role in the occurrence, development and prognosis of septic acute kidney injury (SAKI). We aimed to explore the specific molecular mechanism of S-nitrosoglutathione (SNG) regulating pyroptosis of kidney tubular epithelial cells (KTECs). By constructing a mice model of sepsis, we pretreated them with SNG and used biochemical methods to detect the levels of serum inflammatory factors and mitochondrial reactive oxygen species (mtROS), assessed the severity of kidney injury and KTECs mitochondrial damage, and detected the expression of KTECs pyroptosis-related proteins and sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway proteins. The kidney injury caused by sepsis was significantly aggravated, and the levels of IL-1β, IL-6, IL-18, TNF-α, malondialdehyde (MDA) and mtROS were all increased, accompanied by the decrease of SIRT3 and SOD2 proteins, while NOD-like receptor with pyrin domain 3 (NLRP3), gasdermin D (GSDMD), Caspase-1 proteins expression and the number of KTECs apoptotic cells were all increased. However, after SNG pretreatment, the levels of IL-1β, IL-6, IL-18, TNF-α, MDA and mtROS were all significantly decreased, the expression of SIRT3 and SOD2 proteins were increased, NLRP3, GSDMD, Caspase-1 proteins expression and the number of KTECs apoptotic cells were decreased. SNG protects SAKI by regulating the SIRT3/SOD2/mtROS signaling pathway to inhibit the pyroptosis of KTECs.
DOI: 10.6084/m9.figshare.29039738
title: Prolonged sitting time and all-cause mortality: the mediating and predictive role of kidney function markers

description: To investigate the association between daily sitting time and all-cause mortality, with a focus on the mediating effect and predictive value of the makers relating to kidney. The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2020. The makers relating to kidney were assessed through estimated glomerular filtration rate (eGFR), urine albumin creatinine ratio (UACR), and other relevant markers. A total of 9,707 adults were included in the analysis. There was a significant increase in the levels of blood urea nitrogen (BUN), creatinine, uric acid, osmolality, and UACR with extended daily sitting time, while eGFR significantly decreased. Notably, individuals sitting ≥ 8 h per day exhibited a 67% higher risk of all-cause mortality (HR = 1.67, 95% CI: 1.43–1.94). A nonlinear (L-shaped) relationship was observed between eGFR (<i>p</i> &lt; 0.001) or UACR (<i>p</i> &lt; 0.001) and all-cause mortality. Mediation analysis revealed that eGFR accounted for 20.98% of the association between sitting time and mortality (<i>p</i> &lt; 0.01). An addition of eGFR or UACR would increase the AUC from 0.585 to 0.762 and 0.656, respectively(<i>p</i> &lt; 0.001). The main mortality caused by daily sitting time included chronic lower respiratory diseases, diabetes mellitus, cerebrovascular diseases and heart diseases. Prolonged daily sitting time is significantly associated with an increased risk of all-cause mortality, potentially mediated by impaired kidney function. Incorporating kidney function markers such as eGFR and UACR enhances the predictive value for mortality risk assessment in sedentary populations.
DOI: 10.6084/m9.figshare.29039738.v1
title: Prolonged sitting time and all-cause mortality: the mediating and predictive role of kidney function markers

description: To investigate the association between daily sitting time and all-cause mortality, with a focus on the mediating effect and predictive value of the makers relating to kidney. The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2020. The makers relating to kidney were assessed through estimated glomerular filtration rate (eGFR), urine albumin creatinine ratio (UACR), and other relevant markers. A total of 9,707 adults were included in the analysis. There was a significant increase in the levels of blood urea nitrogen (BUN), creatinine, uric acid, osmolality, and UACR with extended daily sitting time, while eGFR significantly decreased. Notably, individuals sitting ≥ 8 h per day exhibited a 67% higher risk of all-cause mortality (HR = 1.67, 95% CI: 1.43–1.94). A nonlinear (L-shaped) relationship was observed between eGFR (<i>p</i> &lt; 0.001) or UACR (<i>p</i> &lt; 0.001) and all-cause mortality. Mediation analysis revealed that eGFR accounted for 20.98% of the association between sitting time and mortality (<i>p</i> &lt; 0.01). An addition of eGFR or UACR would increase the AUC from 0.585 to 0.762 and 0.656, respectively(<i>p</i> &lt; 0.001). The main mortality caused by daily sitting time included chronic lower respiratory diseases, diabetes mellitus, cerebrovascular diseases and heart diseases. Prolonged daily sitting time is significantly associated with an increased risk of all-cause mortality, potentially mediated by impaired kidney function. Incorporating kidney function markers such as eGFR and UACR enhances the predictive value for mortality risk assessment in sedentary populations.
DOI: 10.6084/m9.figshare.28433699
title: Identification of L-shaped curve association between serum bicarbonate concentrations and short-term outcomes in patients with acute kidney injury: a retrospective cohort study

description: This study aims to investigate the association between serum bicarbonate levels and short-term outcomes in patients with acute kidney injury (AKI), with a focus on 14-day mortality and AKI progression within a 14-day period. We conducted a secondary analysis using data from the Electronic Alerts for Acute Kidney Injury Amelioration (ELAIA) study. Serum bicarbonate levels and their associated outcomes were collected for all participants. Cox regression analysis and smooth curve fitting methods were employed to achieve the research objectives. A total of 5,835 patients with AKI were included in the study. After adjustment for confounding factors, patients with serum bicarbonate concentrations below 22 mmol/L had a higher risk of both 14-day mortality and AKI progression compared to those with levels between 22 and 26 mmol/L (hazard ratio [HR] 1.90; 95% confidence interval [CI], 1.51–1.83 for mortality and HR 1.45; 95% CI, 1.23–1.71 for AKI progression, respectively). In contrast, patients with bicarbonate concentrations above 26 mmol/L had a lower risk of 14-day mortality (HR 0.70; 95% CI, 0.53–0.94) and AKI progression (HR 0.90; 95% CI, 0.74–1.10). Subsequent exploratory subgroup analyses revealed no statistically significant interactions (all <i>p</i>-values for interaction &gt; 0.05) between 14-day mortality and serum bicarbonate levels. In this cohort of AKI patients, serum bicarbonate concentrations below 22 mmol/L were associated with increased risks of 14-day mortality and AKI progression, while concentrations above 26 mmol/L were linked to a reduced risk of 14-day mortality.
DOI: 10.6084/m9.figshare.28509579
title: Efficacy and potential pharmacological mechanism of <i>Astragalus-Salvia miltiorrhiza</i> combination in diabetic nephropathy: integrating meta-analysis, network pharmacology, molecular docking, and experimental validation

description: Diabetic nephropathy (DN) is a diabetes mellitus (DM)-induced complication that poses high morbidity and mortality risks. The <i>Astragalus</i> and <i>Salvia miltiorrhiza</i> couplet medicines (AS) are commonly employed in DN clinical treatment in China, but their clinical efficacy and potential pharmacological mechanisms are yet to be evaluated. A meta-analysis of 15 studies involving 1,443 patients was conducted. Furthermore, network pharmacology predicted components and targets, which were verified by molecular docking and <i>in vivo</i> validation. In our meta-analysis, AS notably elevated clinical outcomes and renal function among patients with DN. Meanwhile, when the treatment duration exceeds 12 weeks, AS demonstrated a significant reduction in fasting blood glucose levels, indicating a time-dependent effect. Moreover, based on network pharmacology results, AS likely enhanced clinical outcomes by interacting with vital signaling pathways, including PI3K/Akt, MAPK, and NF-kappa B. Molecular docking studies have confirmed that PTGS2, the key therapeutic target of AS, can be closely combined with bioactive components <i>GLY</i>, <i>quercetin</i>, <i>apigenin,</i> and <i>daidzein</i>. Additionally, <i>in vivo</i> experiments have corroborated that AS can ameliorate renal function, UACR, and biomarkers associated with iron metabolism, such as GPX4, PTGS2, FTH1, and FTL1. Through rigorous experimental validation, our study demonstrates AS’s significant clinical efficacy in managing DN. Specifically, AS has been shown to enhance renal function, ameliorate renal fibrosis, and positively influence iron metabolism. Despite these promising outcomes, future research with a larger sample size must be conducted to further substantiate these findings.
DOI: 10.6084/m9.figshare.28509579.v1
title: Efficacy and potential pharmacological mechanism of <i>Astragalus-Salvia miltiorrhiza</i> combination in diabetic nephropathy: integrating meta-analysis, network pharmacology, molecular docking, and experimental validation

description: Diabetic nephropathy (DN) is a diabetes mellitus (DM)-induced complication that poses high morbidity and mortality risks. The <i>Astragalus</i> and <i>Salvia miltiorrhiza</i> couplet medicines (AS) are commonly employed in DN clinical treatment in China, but their clinical efficacy and potential pharmacological mechanisms are yet to be evaluated. A meta-analysis of 15 studies involving 1,443 patients was conducted. Furthermore, network pharmacology predicted components and targets, which were verified by molecular docking and <i>in vivo</i> validation. In our meta-analysis, AS notably elevated clinical outcomes and renal function among patients with DN. Meanwhile, when the treatment duration exceeds 12 weeks, AS demonstrated a significant reduction in fasting blood glucose levels, indicating a time-dependent effect. Moreover, based on network pharmacology results, AS likely enhanced clinical outcomes by interacting with vital signaling pathways, including PI3K/Akt, MAPK, and NF-kappa B. Molecular docking studies have confirmed that PTGS2, the key therapeutic target of AS, can be closely combined with bioactive components <i>GLY</i>, <i>quercetin</i>, <i>apigenin,</i> and <i>daidzein</i>. Additionally, <i>in vivo</i> experiments have corroborated that AS can ameliorate renal function, UACR, and biomarkers associated with iron metabolism, such as GPX4, PTGS2, FTH1, and FTL1. Through rigorous experimental validation, our study demonstrates AS’s significant clinical efficacy in managing DN. Specifically, AS has been shown to enhance renal function, ameliorate renal fibrosis, and positively influence iron metabolism. Despite these promising outcomes, future research with a larger sample size must be conducted to further substantiate these findings.
DOI: 10.6084/m9.figshare.28433699.v1
title: Identification of L-shaped curve association between serum bicarbonate concentrations and short-term outcomes in patients with acute kidney injury: a retrospective cohort study

description: This study aims to investigate the association between serum bicarbonate levels and short-term outcomes in patients with acute kidney injury (AKI), with a focus on 14-day mortality and AKI progression within a 14-day period. We conducted a secondary analysis using data from the Electronic Alerts for Acute Kidney Injury Amelioration (ELAIA) study. Serum bicarbonate levels and their associated outcomes were collected for all participants. Cox regression analysis and smooth curve fitting methods were employed to achieve the research objectives. A total of 5,835 patients with AKI were included in the study. After adjustment for confounding factors, patients with serum bicarbonate concentrations below 22 mmol/L had a higher risk of both 14-day mortality and AKI progression compared to those with levels between 22 and 26 mmol/L (hazard ratio [HR] 1.90; 95% confidence interval [CI], 1.51–1.83 for mortality and HR 1.45; 95% CI, 1.23–1.71 for AKI progression, respectively). In contrast, patients with bicarbonate concentrations above 26 mmol/L had a lower risk of 14-day mortality (HR 0.70; 95% CI, 0.53–0.94) and AKI progression (HR 0.90; 95% CI, 0.74–1.10). Subsequent exploratory subgroup analyses revealed no statistically significant interactions (all <i>p</i>-values for interaction &gt; 0.05) between 14-day mortality and serum bicarbonate levels. In this cohort of AKI patients, serum bicarbonate concentrations below 22 mmol/L were associated with increased risks of 14-day mortality and AKI progression, while concentrations above 26 mmol/L were linked to a reduced risk of 14-day mortality.
DOI: 10.6084/m9.figshare.28900074.v1
title: Association between the difference in estimated GFR based on cystatin C versus creatinine in coronary artery diseases

description: The difference in estimated glomerular filtration rate (eGFR) derived from creatinine and cystatin C (eGFR<sub>diff</sub>) has been noticed recently and the relationship with poor cardiovascular prognosis has been proven. However, primary prevention of the risk of coronary artery disease (CAD) is equally important but there is a lack of studies specifically investigating this implication. This prospective cohort study utilized data from the UK Biobank, including 437,536 participants without CAD at baseline. The primary outcome was defined as CAD. The eGFR<sub>diff</sub> was calculated by subtracting creatinine-based eGFR from cystatin C-based eGFR. Participants were then categorized into a negative, intermediate range, and positive group based on thresholds of −15 mL/min/1.73 m<sup>2</sup> and 15 mL/min/1.73 m<sup>2</sup>. Cox proportional risk models were used to evaluate the associations of eGFR<sub>diff</sub> with CAD and the relationship among different genetic risks of CAD. During a median follow-up of 13.8 years, CAD occurred in 36,797 participants. In the fully adjusted model, compared to midrange eGFR<sub>diff,</sub> participants with a positive eGFR<sub>diff</sub> had a lower risk of CAD (HR 0.717, 95%CI 0.675-0.762), while with a negative eGFR<sub>diff</sub> had a higher risk (HR 1.433, 95%CI 1.399-1.468). When eGFR<sub>diff</sub> was treated as a continuous variable, a statistically significant trend toward a lower risk of CAD as eGFR<sub>diff</sub> increased (HR 0.982, 95% CI 0.981-0.982). Moreover, this relationship is independent of genetic susceptibility. eGFR<sub>diff</sub> was associated with CAD risk, where a high eGFR<sub>diff</sub> corresponded to a decreased likelihood of CAD onset no matter genetic susceptibility.
DOI: 10.6084/m9.figshare.28900074
title: Association between the difference in estimated GFR based on cystatin C versus creatinine in coronary artery diseases

description: The difference in estimated glomerular filtration rate (eGFR) derived from creatinine and cystatin C (eGFR<sub>diff</sub>) has been noticed recently and the relationship with poor cardiovascular prognosis has been proven. However, primary prevention of the risk of coronary artery disease (CAD) is equally important but there is a lack of studies specifically investigating this implication. This prospective cohort study utilized data from the UK Biobank, including 437,536 participants without CAD at baseline. The primary outcome was defined as CAD. The eGFR<sub>diff</sub> was calculated by subtracting creatinine-based eGFR from cystatin C-based eGFR. Participants were then categorized into a negative, intermediate range, and positive group based on thresholds of −15 mL/min/1.73 m<sup>2</sup> and 15 mL/min/1.73 m<sup>2</sup>. Cox proportional risk models were used to evaluate the associations of eGFR<sub>diff</sub> with CAD and the relationship among different genetic risks of CAD. During a median follow-up of 13.8 years, CAD occurred in 36,797 participants. In the fully adjusted model, compared to midrange eGFR<sub>diff,</sub> participants with a positive eGFR<sub>diff</sub> had a lower risk of CAD (HR 0.717, 95%CI 0.675-0.762), while with a negative eGFR<sub>diff</sub> had a higher risk (HR 1.433, 95%CI 1.399-1.468). When eGFR<sub>diff</sub> was treated as a continuous variable, a statistically significant trend toward a lower risk of CAD as eGFR<sub>diff</sub> increased (HR 0.982, 95% CI 0.981-0.982). Moreover, this relationship is independent of genetic susceptibility. eGFR<sub>diff</sub> was associated with CAD risk, where a high eGFR<sub>diff</sub> corresponded to a decreased likelihood of CAD onset no matter genetic susceptibility.