Enzo Pereira de Lima

Extracellular vesicles (EVs) are membrane-bound structures released by cells carrying diverse biomolecules involved in intercellular communication. Small EVs are abundant in body fluids, playing a key role in cell signaling. Their natural occurrence and therapeutic potential, especially in the context of muscular disorders, make them a significant area of research. Sarcopenia, characterized by progressive muscle fiber loss, represents a pathological state in which EVs could offer therapeutic benefits, reducing morbidity and mortality. Recent studies have proposed an interplay between adipose tissue (AT) and skeletal muscle regarding sarcopenia pathology. AT dysregulation, as seen in obesity, contributes to skeletal muscle loss in a multifactorial way. While AT-derived stem cell (ATDSC) small EVs have been implicated in musculoskeletal homeostasis, their precise action in muscle regeneration remains incompletely understood. In this context, ATDSC-derived small EVs can stimulate skeletal muscle regeneration through improved proliferation and migration of muscle cells, enhancement of muscular perfusion, improvement of tendon and nerve regeneration, stimulation of angiogenesis, and promotion of myogenic differentiation. However, they can also increase skeletal muscle loss. Notably, this is the first comprehensive review to systematically examine the role of ATDSC-derived small EVs in sarcopenia.

Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB’s effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB’s ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes.