Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.

This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway. This elaborate system encompasses ligands, receptors, and binding proteins, giving rise to a wide array of functions, including aspects such as carcinogenesis and chemoresistance. Detailed genetic analysis of IR and IGFR structures highlights their distinct isoforms, which arise from alternative splicing and exhibit diverse affinities for ligands. Notably, the overexpression of the IR-A isoform is linked to cancer stemness, tumor development, and resistance to targeted therapies. Similarly, elevated IGFR expression accelerates tumor progression and fosters chemoresistance. The review underscores the intricate interplay between IRs and IGFRs, contributing to resistance against anti-IGFR drugs. Consequently, the dual targeting of both receptors could present a more effective strategy for surmounting chemoresistance. To conclude, this review brings to light the pivotal roles played by IRs and IGFRs in cellular signaling, carcinogenesis, and therapy resistance. By precisely modulating these receptors and their complex signaling pathways, the potential emerges for developing enhanced anti-cancer interventions, ultimately leading to improved patient outcomes.

Suicidal thoughts and behaviors in the Kingdom of Saudi Arabia.

OBJECTIVE: Suicidal thoughts and behaviors (STB) constitute an escalating public health concern globally. Despite the growing burden of suicidal ideation, plan, and attempts, national information on the trends of STB is lacking in the Kingdom of Saudi Arabia (KSA). Therefore, we aim to report on the prevalence, correlates, and treatment-seeking behaviors associated with STB in the country using nationally representative information from The Saudi National Mental Health Survey (SNMHS). METHODS: The SNMHS is a national household survey of Saudi citizens aged 15-65 (n = 4004). The adapted Composite International Diagnostic Interview (CIDI) 3.0 was administered to produce lifetime and 12-month prevalence and treatment estimates of STB in the KSA. Associated correlates were calculated using cross tabulations and logistic regressions. RESULTS: Suicidal ideation, plan, and attempt had respective lifetime prevalence rates of 4.90 %, 1.78 %, and 1.46 %; 12-month prevalence rates of 1.82 %, 0.89 %, and 0.63 %. Significant correlates of STB include younger age, female gender, low education, urban rearing, and singe marital status. STB were also significantly associated with the presence of prior mental disorders, childhood adversities, and low treatment-seeking. CONCLUSIONS: High unmet need and significant sociocultural and psychological risk factors have been identified in association with STB in the KSA. Given the community-based nature of the SNMHS and the limited national data on STB in the Middle East and North Africa region, our findings can extend to inform the necessary healthcare policies, treatment plans, and prevention strategies needed to alleviate the burdens of STB in the region.