We investigated how aging interacts with high-fat (HFD) and ketogenic (KD) diets to influence functional overload (FO)-induced muscle hypertrophy in C57BL/6J mice. Male mice aged 3, 16, and 24 months were fed regular chow (RD), HFD, or KD for 12 weeks, with FO of the plantaris muscle induced by denervation of the soleus and gastrocnemius during the final 6 weeks (n = 8-10 per group). Muscle hypertrophy was unaffected by diet (p = 0.897) but declined with age (p < 0.001), with a marked reduction already in mature mice. Plasma IGF-1 was higher in adult than mature (p < 0.05) and old (p < 0.001) mice and correlated positively with hypertrophy (r = 0.29, p = 0.01). The weak correlation of hypertrophy with plasma IGF-I levels suggests that IGF-I is only one among many factors playing a role in muscle hypertrophy.
Vertebrate evolution from a single multipurpose cloaca to separate urogenital and anal openings remains a central molecular question with relevance to reproductive diversification and anorectal malformations. We investigated BMP7, a critical regulator of cloacal formation, across 37 vertebrates from cartilaginous fish to mammals using phylogenetics, sequence alignment, physicochemical assessment, domain analysis, motif analysis and molecular docking. The BMP7 core TGF-beta domain was highly conserved (>90% identity), whereas peripheral regions showed significant habitat-associated divergence (p < 0.01), including shifts in isoelectric point between aquatic and terrestrial vertebrates (pI 6.22-6.97 to 6.98-8.98) and altered stability indices. A key finding was that placental mammals, in which cloacal septation produces distinct anorectal and urogenital outlets, showed lineage-specific amino-acid changes, including Pro111Ala, linked to predicted BMP7-FOXA1 regulatory refinement. MEME analysis identified mammal-bird GWQDWI conservation and amphibian-reptile RACGCH divergence, supporting peripheral BMP7 adaptation during cloacal evolution.
Research increasingly implicates neuroimmune inflammation in schizophrenia, with the epidermal growth factor (EGF) family as a potential link. This review critically evaluates EGF family members as diagnostic, risk, and treatment response markers.The most consistent finding is decreased serum EGF in chronic schizophrenia, confirmed in postmortem brain and independent of antipsychotics. First-episode data are heterogeneous, reflecting differences in medication status, population, and illness stage.Genetic studies of EGF rs4444903 show no consistent disease risk association but demonstrate a replicable, sex-specific effect on age at onset in males. Stronger evidence implicates NRG1 type IV and NRG3 polymorphisms in disease biology.Serum EGF is not a reliable treatment response marker. In summary, EGF alone is not clinically useful. Its value lies in consistent reduction in chronic patients, sex-specific effects on age at onset, and robust links of NRG1 and NRG3 to schizophrenia.
ERK, a core member of the MAPK family, operates through the classical Ras/Raf/MEK/ERK signaling cascade. Abnormal activation of this pathway is closely associated with malignant tumor progression and represents a critical target in anticancer drug development. In this article, we systematically describe the regulatory network of the ERK pathway, including negative feedback mechanisms, cross-pathway interactions, non-coding RNAs, and epigenetic regulation, with a particular focus on ERK's dual role-promoting both cell proliferation and apoptosis-in pituitary adenomas compared to other tumors. Additionally, we explore emerging ERK-targeted therapies and their associated resistance mechanisms. Despite substantial research on ERK, further investigation into its underlying mechanisms is warranted. We propose the construction of computational modeling approaches to analyze these complex regulatory relationships and to develop precise combination therapies aimed at overcoming resistance. Such strategies could enable personalized treatment and offer more effective solutions for managing pituitary tumors and other malignancies.
Endometriosis, a chronic inflammatory condition linked to pelvic pain and infertility, is characterized by immune dysfunction involving dysregulated apoptosis and cell proliferation. This case-control study included 87 infertile women undergoing diagnostic laparoscopy and assessed serum and peritoneal levels of sEGFR, sFas, and sFasL using ELISA. Pain intensity was evaluated via the Visual Analog Scale (VAS). Peritoneal sFasL concentrations were significantly higher in infertile women with pelvic pain (p = 0.012) and correlated with VAS scores (r = 0.261, p = 0.014). Serum and peritoneal sFasL levels were significantly elevated in endometriosis patients with pelvic pain compared to controls (p = 0.003, p = 0.002, respectively). Peritoneal sFasL levels were also associated with dysmenorrhea and dyspareunia. ROC analysis demonstrated that serum sFasL differentiated endometriosis from controls (AUC = 0.797, p < 0.001). These findings suggest that sFasL may serve as a potential noninvasive biomarker for endometriosis. Further research should investigate its regulatory role in endometriosis-related pain.
