Targeting apoptosis and unfolded protein response: the impact of ß-hydroxybutyrate in clear cell renal cell carcinoma under glucose-deprived conditions.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) plays a significant role in the mortality associated with kidney cancer. Targeting biological processes that inhibit cancer growth opens up new treatment possibilities. The unfolded protein response (UPR) and apoptosis have crucial roles in RCC progression. This study investigates the impact of ß-hydroxybutyrate (BHB) on ccRCC cells under glucose deprivation resembling as a ketogenic diet. METHOD: Caki-1 ccRCC cells were exposed to decreasing glucose concentrations alone or in combination with 10 or 25 mM BHB during 48 and 72 h. Cell viability was determined using MTT assay. The mRNA expression level of apoptosis-and UPR-related markers (Bcl-2, Bax, caspase 3, XBP1s, BIP, CHOP, ATF4, and ATF6) were assayed by qRT-PCR. RESULTS: Cell viability experiments demonstrated that combining different doses of BHB with decreasing glucose levels initially improved cell viability after 48 h. Nevertheless, this trend reversed after 72 h, with higher impacts disclosed at 25 mM BHB. Apoptosis was induced in BHB-treated cells as caspase-3 and Bax were increased and Bcl-2 was downregulated. BHB supplementation reduced UPR-related gene expression (XBP1s, BIP, CHOP, ATF4, and ATF6), revealing a possible mechanism by which BHB affects cell survival. CONCLUSION: This research emphasizes the dual effect of BHB, initially suppressing cell- survival under glucose deprivation but eventually triggering apoptosis and suppressing UPR signaling. These data highlight the intricate connection between metabolic reprogramming and cellular stress response in ccRCC. Further research is recommended to explore the potential of BHB as a therapeutic strategy for managing ccRCC.

Insulin receptor substrate 2 gene Gly1057Asp polymorphism is a risk factor for nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), which is an emerging global chronic liver disease, has a close association with insulin resistance. We aimed to determine whether the Gly1057Asp (rs1805097) polymorphism of the insulin receptor substrate 2 (IRS2) gene is associated with NAFLD. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism method, 135 patients with biopsy-proven NAFLD and 135 controls underwent IRS2 genotype analysis. RESULTS: Genotype and allele distributions of the IRS2 gene Gly1057Asp variant conformed to the Hardy-Weinberg equilibrium in both the case and control groups (P > .05). The Asp/Asp genotype of IRS2 gene Gly1057Asp polymorphism compared with Gly/Gly genotype was associated with a 2.1-fold increased risk for NAFLD after adjustment for confounding factors (P = .029; odds ratio = 2.10, 95% CI = 1.23-3.97). CONCLUSION: Our findings revealed for the first time that the Gly1057Asp Asp/Asp genotype of the IRS2 gene is a marker of increased NAFLD susceptibility; however, studies in other populations are required to confirm the results.

Comparisons between Insomnia Incidence after Coronary Artery Bypass Graft Surgery with Coronary Angioplasty.

BACKGROUND: The aim of this study was to investigate the incidence of insomnia after coronary angioplasty and coronary artery bypass graft surgery (CABG) and compare them. MATERIALS AND METHODS: This cross-sectional study was done in Masih Daneshvari and Emam Hossein Hospital of Tehran during a period of 12 months in 2016. The study group consisted of patients who were admitted to these hospitals with heart disease and had to go under CABG or angioplasty. Each participant completed a detailed Persian version of the insomnia severity index and demographic questionnaire which includes demographic questions and questions about the onset or durability of sleep as well as questions about the use of alcohol, caffeine, cigarettes, and sleeping drugs 2 days before the surgery and 1 week after that. The state of insomnia was measured before and after the CABG and compared with the state of insomnia before and after angioplasty. RESULTS: About 150 patients were included in the study (80 men [67.4%] and 70 women [43.6%]). In the CABG group, 14.67% of the preoperative patients and 24.0% of the patients after the operation had insomnia, and the difference between them was significant (P = 0.003). Furthermore, in the angioplasty group, 14.67% of the preoperative patients and 20.0% of the patients after the operation had insomnia, and the difference between them was significant (P = 0.001). CONCLUSION: Insomnia after both CABG and angioplasty was significantly increased but in CABG group this increase was more than angioplasty.