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Sirtuin 6 (SIRT6) can inhibit the fibrosis of many organs. However, the relationship between SIRT6 and peritoneal fibrosis (PF) in peritoneal dialysis (PD) remains unclear. We collected 110 PD patients with a duration of PD for more than 3 months and studied the influence of PD duration and history of peritonitis on SIRT6 levels in PD effluents (PDEs). We also analyzed the relationship between SIRT6 levels in PDEs and transforming growth factor beta 1 (TGF-β1), IL-6, PD duration, peritoneal function, PD ultrafiltration (UF), and glucose exposure. We extracted human peritoneal mesothelial cells (HPMCs) from PDEs and measured the protein and gene expression levels of SIRT6, E-cadherin, vimentin, and TGF-β1 in these cells. Based on the clinical results, we used human peritoneal mesothelial cells lines (HMrSV5) to observe the changes in SIRT6 levels and mesothelial-to-mesenchymal transition (MMT) after intervention with PD fluid. By overexpressing and knocking down SIRT6 expression, we investigated the effect of SIRT6 expression on E-cadherin, vimentin, and TGF-β1 expression to elucidate the role of SIRT6 in mesothelial-to-epithelial transition in PMCs. Results: (1) With the extension of PD duration, the influence of infection on SIRT6 levels in PDEs increased. Patients with the PD duration of more than 5 years and a history of peritonitis had the lowest SIRT6 levels. (2) SIRT6 levels in PDEs were negatively correlated with PD duration, total glucose exposure, TGF-β1, IL-6 levels, and the dialysate-to-plasma ratio of creatinine (Cr4hD/P), but positively correlated with UF. This indicates that SIRT6 has a protective effect on the peritoneum. (3) The short-term group (PD ≤ 1 year) had higher SIRT6 and E-cadherin gene and protein levels than the mid-term group (1 year < PD ≤ 5 years) and long-term group (PD > 5 years) in PMCs, while vimentin and TGF-β1 levels were lower in the mid-term group and long-term group. Patients with a history of peritonitis had lower SIRT6 and E-cadherin levels than those without such a history. (4) After 4.25% PD fluid intervention for HPMCs, longer intervention time resulted in lower SIRT6 levels. (5) Overexpressing SIRT6 can lead to increased E-cadherin expression and decreased vimentin and TGF-β1 expression in HPMCs. Knocking down SIRT6 expression resulted in decreased E-cadherin expression and increased vimentin and TGF-β1 expression in HPMCs. This indicates that SIRT6 expression can inhibit MMT in HPMCs, alleviate PF associated with PD, and have a protective effect on the peritoneum. [ABSTRACT FROM AUTHOR]

NSCLC is the first cause of cancer-related deaths in China and threatens life expectancy of the people. Novel drugs and treatment strategies are urgently required. Capsaicin is noticed as a potential new drug for lots of tumors due to its anti-proliferative effect on cancer cells. Our study evaluated the roles of capsaicin in NSCLC cells (A549 and NCI-H23) and further explored its underlying mechanisms. Effect of capsaicin treatment on cell viability was determined by MTT assay and IC50 values for A549 and NCI-H23 cells were ascertained. The iron kit detected the total iron levels and the ferric divalent ions levels in A549 and NCI-H23 cells. GSH kit was used to detect the expression of GSH in A549 and NCI-H23 cells. Additionally, mRNA and protein levels of SLC7A11 and GPX4 were analyzed by real-time PCR and western blot analysis. Through MTT assay, we found that 200 μM capsaicin in cultured A549 cells for 48 h could reach the IC50 value, and the condition was 100 μM and 48 h for NCI-H23 cells. Capsaicin increased total iron levels and ferrous ion levels in A549 and NCI-H23 cells in contrast with the control group, whereas the levels of GSH was reduced in contrast with the control group. Besides, mRNA and protein levels of SLC7A11 and GPX4 were decreased significantly in A549 and NCI-H23 cells treated with capsaicin in contrast with the control group. Our study indicated that capsaicin inhibited the proliferation of A549 and NCI-H23 cells and induced ferroptosis by inactivating SLC7A11/GPX4 signaling. Capsaicin could be used as a potential anticancer agent in the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10?11, OR = 1.21; rs4227, P = 4.31 × 10?10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10?14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and ?-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10?20, OR = 1.34; rs1794275, P = 3.43 × 10?13, OR = 1.30; rs2523946, P = 1.74 × 10?11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10?11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation. [ABSTRACT FROM AUTHOR]