👤 Jorge García-García

Intrinsic Capacity (IC) is defined as the composite of physical and mental abilities an individual possesses, encompassing five domains: cognition, psychological health, sensory function, vitality, and locomotion. This construct is central to the World Health Organization's framework for assessing functional ability in older adults. Growing evidence highlights the critical role of the musculoskeletal system in maintaining these domains, while conditions such as sarcopenia, osteoporosis, and their coexistence as osteosarcopenia (OS) are increasingly associated with IC decline. This narrative review compiles current evidence on the modulatory role of muscles and bones in IC and the impacts of sarcopenia, osteoporosis, and OS. Most findings suggest that musculoskeletal tissues influence IC not only through biomechanical functions but also as secretory organs, releasing myokines and osteokines with endocrine, paracrine, and autocrine effects. Among the most studied are brain-derived neurotrophic factor, irisin, osteocalcin, and interleukin-6. Dysregulation of these pathways, along with biomechanical dysfunction and systemic inflammation, links sarcopenia, osteoporosis, and OS to IC impairment. Further research is needed to clarify the specific mechanisms involved, particularly in the sensory and vitality domains, to inform targeted interventions that promote healthy aging. Show less

Oral leukoplakia and proliferative verrucous leukoplakia represent oral potentially malignant disorders. Oral leukoplakia typically presents as solitary lesions, while proliferative verrucous leukoplakia manifests as multifocal lesions with higher malignant potential. This study aimed to investigate the genetic heterogeneity between these disorders through differential gene expression, genetic variants, and microRNA profiling to identify potential biomarkers for diagnosis and prognosis. Biopsies and peripheral blood samples were obtained from 20 patients. Subsequently, RNA extraction, RNA-Seq libraries preparation, and bioinformatic analyses were conducted to ascertain differential gene expression, genetic variants, and microRNA expression. In mRNA analysis, overexpressed genes in proliferative verrucous leukoplakia are primarily associated with inflammation and immune regulation, while underexpressed genes relate to skin barrier maintenance. Pathway analysis reveals underexpressed genes related to impaired keratinization in proliferative verrucous leukoplakia and with keratin envelope formation in oral leukoplakia, while overexpressed genes are linked to synaptic processes and protein-protein interactions. Somatic mutation drivers in proliferative verrucous leukoplakia include variants in NRXN3, SRGAP2B, INIP, MYO18A, and ATF7IP genes. Regarding variant analysis, two variants in the Syndecan 3 (SDC3) gene identified in proliferative verrucous leukoplakia have demonstrated enormous value and indicate an important biomarker for a differential diagnosis and to predict prognosis. Proliferative verrucous leukoplakia shows in miRNA analysis MIR1246 and MIR767 overexpression, with MIR135B being the most underexpressed. Our findings emphasize the intricate transcriptomic profiles in oral leukoplakia and proliferative verrucous leukoplakia development, laying the groundwork for future studies to enhance clinical management and patient outcomes in oral oncology. Syndecan 3 gene polymorphisms may represent a key point in proliferative verrucous leukoplakia differential diagnosis and prognostic prediction. Show less

Cancer stem cells (CSCs) play a key role in the progression of colorectal cancer (CRC). The high heterogeneity of CSCs has hindered the clinical application of CSC-targeting therapies. Tetracyclines are drugs with therapeutic potentials beyond their antibiotic activity. We previously demonstrated the efficacy of tigecycline, a third-generation tetracycline, against a model of colitis-associated colorectal cancer, primarily focusing on its immunomodulatory role with a preliminary assessment of its impact on stemness. In this study we characterize the effects of tigecycline on colon CSCs in vitro and in a CRC xenograft model, with special attention on the signaling pathways involved and the modulation of the gut microbiota. We generated secondary colonospheres from two colon tumor cell lines HCT116 and CMT93, and evaluated the effect of tigecycline on CSCs properties. We showed that tigecycline (25, 50 μM) effectively reduced colon CD133 Show less