Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.

Pancreatic ductal adenocarcinoma (PDAC) is poised to become the second leading cause of cancer-related death by 2030, necessitating innovative therapeutic strategies. Genetic and epigenetic alterations, including those involving the COMPASS-like complex genes, have emerged as critical drivers of PDAC progression. This review explores the genetic and epigenetic landscape of PDAC, focusing on the role of the COMPASS-like complex in regulating chromatin accessibility and gene expression. Specifically, we delve into the functions of key components such as KDM6A, KMT2D, KMT2C, KMT2A, and KMT2B, highlighting their significance as potential therapeutic targets. Furthermore, we discuss the implications of these findings for developing novel treatment modalities for PDAC.

Genome, Metabolism, or Immunity: Which Is the Primary Decider of Pancreatic Cancer Fate through Non-Apoptotic Cell Death?

Pancreatic ductal adenocarcinoma (PDAC) is a solid tumor characterized by poor prognosis and resistance to treatment. Resistance to apoptosis, a cell death process, and anti-apoptotic mechanisms, are some of the hallmarks of cancer. Exploring non-apoptotic cell death mechanisms provides an opportunity to overcome apoptosis resistance in PDAC. Several recent studies evaluated ferroptosis, necroptosis, and pyroptosis as the non-apoptotic cell death processes in PDAC that play a crucial role in the prognosis and treatment of this disease. Ferroptosis, necroptosis, and pyroptosis play a crucial role in PDAC development via several signaling pathways, gene expression, and immunity regulation. This review summarizes the current understanding of how ferroptosis, necroptosis, and pyroptosis interact with signaling pathways, the genome, the immune system, the metabolism, and other factors in the prognosis and treatment of PDAC.

Association of indoor use of pesticides with CKD of unknown origin.

INTRODUCTION: Chronic kidney disease (CKD) is a growing global health problem. Recently, an epidemic of CKD of unknown origin (CKDu), a form of CKD seen mostly in agricultural communities, has been emerged. One of the proposed causes of CKDu is pesticide use in farmers. On the other hand, the research on relation between indoor use of pesticides and CKDu is little. In this study, we aimed to investigate the association between indoor use of pesticide as well as the exposure time with CKDu. This study was done as part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. All subjects with diabetes mellitus and/or hypertension, estimated glomerular filtration rate (eGFR) between 60-89 ml/min/1.73 m2, and unavailable creatinine measurement were excluded. Subjects with an eGFR of less than 60 ml/min/1.73 m2 were defined as having CKDu, and their data were compared with those with an eGFR of more than 90 ml/min/1.73 m2. Data regarding indoor pesticide use and duration of exposure were obtained through a questionnaire. After applying the exclusion criteria, 1079 subjects remained in the study. Female sex, single marital status, low physical activity, triglyceride (TG) levels of more than 150 mg/dl, body mass index (BMI) of more than 25 kg/m2, non-smokers, indoor pesticide use, and high pesticide exposure time were associated with CKDu. The effects of age, female sex, TG levels more than 150 mg/dl, pesticide use (OR 1.36; 95% CI 1.01-1.84), and high exposure time (third tertile of exposure time) compared to non-users (OR 1.64; 95% CI 1.07-2.51) remained significant in multivariable analysis. CONCLUSION: We found a positive association between pesticide use, as well as longer exposure time to pesticides, and impaired kidney function in cases without diabetes mellitus and hypertension. Further longitudinal studies should be carried out to confirm these findings.