The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin’s lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis.

BACKGROUND: Perirenal adipose tissue (PRAT) consists of white and brown adipocytes with good vascularization and dense innervation, which could influence the blood pressure. We aim to investigate the association of PRAT thickness with risks of overall and specific forms of hypertension. METHODS: We measured PRAT thickness in the UK Biobank and CONPASS (Chongqing Primary Aldosteronism Study). We prospectively examined the correlation between PRAT thickness and incident hypertension in the UK Biobank. We cross-sectionally explored associations between PRAT thickness and common forms of hypertension in CONPASS. Integrating data from GWAS (Genome-Wide Association Study), we investigated the potential causal relationship between PRAT and hypertension forms by 2-sample Mendelian randomization analyses. RESULTS: In the prospective analysis of the UK Biobank, participants whose PRAT thickness was ≥46.1 mm showed a higher risk of developing hypertension than participants whose PRAT thickness was <16.4 mm (hazard ratio, 2.91 [95% CI, 1.97–4.32]). In the cross-sectional analysis of CONPASS, a 1 SD increment in PRAT thickness was associated with a 2.77-fold higher adjusted odds of low-renin essential hypertension and a 3.89-fold higher adjusted odds of idiopathic hyperaldosteronism. PRAT thickness was not significantly associated with other forms of hypertension, such as aldosterone-producing adenoma and obstructive sleep apnea. In 2-sample Mendelian randomization analyses, PRAT thickness was only significantly associated with a higher risk of idiopathic hyperaldosteronism (inverse variance weighted odds ratio, 1.33 [95% CI, 1.09–1.62]), with no evidence of significant heterogeneity or substantial directional pleiotropy. CONCLUSIONS: PRAT is causally associated with idiopathic hyperaldosteronism rather than essential hypertension and other forms of secondary hypertension.

Background: There is still a lack of enough evidence about Nogo‐B levels and vascular complications in patients with type 2 diabetes. Our first aim was to assess the levels of Nogo‐B in type 2 diabetes mellitus (T2DM) patients with or without vascular complications (VC). Our second aim was to determine the mechanism by which Nogo‐B may protect vasculature using a hyperglycemic HUVEC model. Methods: Sera or samples of patients with T2DM and subjects without diabetes were collected from the First or Second Affiliated Hospital of Chongqing Medical University. Human umbilical endothelial cells (HUVECs) were purchased and treated with high glucose (HG) and/or cholesterol (C) before and after Nogo‐B knockdown or overexpression. Graphpad and SPSS version 27 software were used for statistical analyses. Results: T2DM patients with vascular complications (DM + VC) displayed significantly lower levels of Nogo‐B when compared with T2DM patients without VC (DM) or subjects without diabetes (NC) ( p < 0.001). In addition, lower levels of Nogo‐B were independently associated with diabetes and/or VC in T2DM patients. Nogo‐B overexpression reduced the expression of mesenchymal markers (α‐SMA and Collagen‐1), TGF‐β1 and P‐smad2/3, while increasing the expression of endothelial markers (CD31, eNOS and VWF) in HUVECs treated with HG and/or C. Conclusion: Our study has proved that lower levels of Nogo‐B are independently associated with VC in T2DM patients. In an in vitro model, Nogo‐B alleviates endothelial cell injury by affecting TGF‐β signalling. Further studies are still needed to support or verify our findings.

Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications.

Adipokines serve crucial functions in diabetic kidney disease (DKD) pathogenesis. Growth differentiation factor 5 (GDF5) is highly expressed in adipose tissue, but its specific role in DKD is unknown. In this study, we observed elevated GDF5 expression in both patients with DKD and db/db mice, suggesting a potential association between GDF5 and DKD progression. Elevated plasma GDF5 levels are associated with an increased risk of incident chronic kidney disease in patients with type 2 diabetes. In animal studies, adipose-specific overexpression of GDF5 increased circulating GDF5 and exacerbated renal injury in db/db mice, characterized by increased tubulointerstitial injury and inflammation infiltration. Conversely, adipose-specific knockdown reduced circulating GDF5 and alleviated renal injury. In vitro studies demonstrated that GDF5 induces partial epithelial–mesenchymal transition in renal tubular epithelial cells via activation of the SMAD1/5/8 signaling pathway, as evidenced by reduced E-cadherin expression and increased Snail1 levels. Notably, the supernatant from GDF5-treated injured HK-2 cells was found to enhance the secretion of proinflammatory cytokines by macrophages. These findings suggest that adipose-derived GDF5 acts as a novel mediator contributing to tubulointerstitial injury in DKD. Article Highlights: Elevated growth differentiation factor 5 (GDF5) expression is correlated with disease progression in both patients with diabetic kidney disease and db/db mice. Adipose-specific GDF5 overexpression exacerbates, whereas its knockdown alleviates, renal tubulointerstitial injury in vivo. GDF5 directly induces partial epithelial–mesenchymal transition in tubular cells by activating the SMAD1/5/8 signaling pathway. Tubular cells exposed to GDF5 release factors that promote proinflammatory cytokine secretion in macrophages.