Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity, which leads to progressive heart failure. Calcium (Ca2+) is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC), but not other Ca2+ regulatory proteins (SERCA or RYR), induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle activity in vitro, in human cardiac slices, and in vivo. Mechanistically, LTCC inhibition by RRAD induces the cell cycle in CMs by modulating calcineurin activity and translocating Hoxb13 to the CM nucleus. Together, this represents a robust pathway for regenerative strategies.

The prevalence of substance abuse and associated factors among male prisoners in Karachi jails, Pakistan.

Objective: Substance abuse and cigarette smoking are now regarded as major public health problems. This study aims to determine the prevalence, risk profile, and associated sociodemographic factors of substance abuse among male prisoners in Karachi jails. Methods: This descriptive cross-sectional study was carried out among 600 male prisoners in Malir and Central Jails in Karachi. The principal investigator collected the data via one-on-one basis interviews, using a survey questionnaire consisting of the WHO ASSIST version 3, and structured demographic proforma. The data analysis regarding ever and current use of ten substances was done according to the standard instruction manual. A Chi-square test was applied to determine the association between categorical sociodemographic variables and current/ever substance use among prisoners. A p-value of <0.05 was considered statistically significant. Results: In this study, 97.1% of prisoners had a history of substance abuse at least once in their lifetime. For the current use of a substance, the majority of the prisoners fell into the low-risk category, except for tobacco for which 80.5% of prisoners were at moderate risk of use. 13%, 12.7%, and 9.5% of prisoners were at high risk for using opioids, cannabis, and tobacco, respectively. Several associations were found between the socioeconomic factors of the study subjects and their substance use. Conclusion: The study demonstrates a high prevalence and alarming current risk profile of substance abuse among prisoners of Karachi Jails. Considering the associated disease burden, substance abuse among prisoners should be considered a public health priority. Further exploration of associated and causative factors can help policymakers devise adequate measures for prevention and rehabilitation.