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Cellular Senescence in Lung Cancer: Molecular Mechanisms and Therapeutic Interventions

4 days 22 hours ago
Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two primary types exist where non-small cell lung cancer (NSCLC), accounts for 80-85% and SCLC accounts for 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Smoking, second-hand smoke, radon gas, asbestos, and other pollutants, genetic predisposition, and COPD are lung cancer risk factors. On the other hand, stresses such as DNA...
Saurav Kumar Jha

Thbs1 regulates skeletal muscle mass in a TGFβ-Smad2/3-ATF4-dependent manner

4 days 22 hours ago
Loss of muscle mass is a feature of chronic illness and aging. Here, we report that skeletal muscle-specific thrombospondin-1 transgenic mice (Thbs1 Tg) have profound muscle atrophy with age-dependent decreases in exercise capacity and premature lethality. Mechanistically, Thbs1 activates transforming growth factor β (TGFβ)-Smad2/3 signaling, which also induces activating transcription factor 4 (ATF4) expression that together modulates the autophagy-lysosomal pathway (ALP) and...
Davy Vanhoutte

Immunological regulation of skeletal muscle adaptation to exercise

6 days 22 hours ago
Exercise has long been acknowledged for its powerful disease-preventing, health-promoting effects. However, the cellular and molecular mechanisms responsible for the beneficial effects of exercise are not fully understood. Inflammation is a component of the stress response to exercise. Recent work has revealed that such inflammation is not merely a symptom of exertion; rather, it is a key regulator of exercise adaptations, particularly in skeletal muscle. The purpose of this piece is to provide...
P Kent Langston

Senescence-Associated Secretory Phenotype (SASP) and Uterine Fibroids: Association with PD-L1 Activation and Collagen Deposition

6 days 22 hours ago
Uterine fibroids (or uterine leiomyoma, UFs) are one of the most prevalent benign uterine tumors with high proliferation and collagen synthesis capabilities. UFs are a significant worldwide health issue for women, affecting their physical and financial well-being. Risk factors for UFs include age, racial disparities, obesity, uterine infections, hormonal variation, and lifestyle (i.e., diet, exercise, stress, and smoking). Senescence and its associated secretory phenotypes (SASPs) are among the...
Eslam E Saad

Sprouty1 is a broad mediator of cellular senescence

6 days 22 hours ago
Genes of the Sprouty family (Spry1-4) restrain signaling by certain receptor tyrosine kinases. Consequently, these genes participate in several developmental processes and function as tumor suppressors in adult life. Despite these important roles, the biology of this family of genes still remains obscure. Here we show that Sprouty proteins are general mediators of cellular senescence. Induction of cellular senescence by several triggers in vitro correlates with upregulation of Sprouty protein...
Carlos Anerillas

Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation

6 days 22 hours ago
A sharp drop in lenticular glutathione (GSH) plays a pivotal role in age-related cataract (ARC) formation. Despite recognizing GSH's importance in lens defense for decades, its decline with age remains puzzling. Our recent study revealed an age-related truncation affecting the essential GSH biosynthesis enzyme, the γ-glutamylcysteine ligase catalytic subunit (GCLC), at aspartate residue 499. Intriguingly, these truncated GCLC fragments compete with full-length GCLC in forming a heterocomplex...
Zongbo Wei

Structural insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies

6 days 22 hours ago
Roco proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson's disease. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Several...
Christian Galicia