Cells

Tunneling nanotubes (TNTs) are thin, actin-based intercellular bridges that enable long-range communication during cellular stress; yet the molecular pathway controlling their formation remains unclear. Here, using gain- and loss-of-function approaches in Cath. a-differentiated (CAD) neuronal cells, we identified a unidirectional regulatory pathway in which myosin-X (Myo10) functions upstream of the actin-bundling protein L-(LCP1) to drive TNT formation. Using Western blotting and fluorescence microscopy, we determined that overexpression of L-plastin significantly increased the proportion of TNT-connected cells, whereas L-plastin downregulation reduced TNT formation, demonstrating that L-plastin is both sufficient and necessary for maintaining normal TNT abundance. Having previously shown that Myo10 is required for TNT formation in CAD cells, we asked whether the relationship is reciprocal. Overexpression/downregulation of L-plastin had no effect on Myo10 protein levels. Conversely, Myo10 downregulation decreased endogenous L-plastin by ~30%, and Myo10 overexpression elevated L-plastin expression and TNT number, demonstrating that Myo10 acts as an upstream regulator of L-plastin. Dual-color 3D imaging revealed co-localization of Myo10 and L-plastin along TNT shafts and filopodia-like precursors (Proto-TNTs). Together, these findings demonstrate that Myo10-dependent TNT formation requires the bundling protein L-plastin, providing a framework for how stress-induced signaling cascades couple TNT initiation to actin-core stabilization during stress and disease.

Despite tremendous scientific efforts aimed at glioblastoma’s (GB) ability to escape therapeutic attempts, the concern remains unsolved. Postbiotics, metabolites, and macromolecules of probiotic bacteria could become adjuvant therapeutics both dealing with cellular events constituting tumor therapy escape mechanisms and protecting normal cells from therapy-induced damage. The study aims to evaluate the dual potential of postbiotics obtained from lactic acid bacteria, L. plantarum and L. rhamnosus, on patient-derived and commercially available GB and normal cells alone and in combination with chemotherapeutic and irradiation oncotreatment regimens. Postbiotic mixtures (PMs) show cytoprotective potential against a new anti-cancer agent—ARA12—on astrocytes and cytoprotective action to irradiated normal fibroblast cells. Although GB cells’ apoptotic response varied between patient-derived cells, both PMs exert cytotoxic or cytostatic effects alone and, in most of the studied therapeutic combinations, on all tested GB cell lines. In particular, L. plantarum PM alleviates treatment escape, possibly shifting the tumor drug response from senescence to apoptosis. The results suggest that postbiotic-based adjunctive treatment could potentiate the therapeutic effect toward neoplastic cells, while alleviating chemotherapy’s adverse effects, helping clinicians to tackle the issue of therapy resistance and improve patients’ comfort.

Kidney aging is receiving growing attention in middle- to high-income societies due to increasing longevity in general population. Chronic Kidney Disease (CKD) has been widely accepted as a major non-communicable human disease affecting over 10% of the adult population in industrialized countries. CKD is mainly caused by metabolic and cardiovascular disorders such as diabetes mellitus and hypertension, disproportionally affecting older people, whereas natural kidney aging is driven by age-dependent systemic and renal low-grade inflammation. Interleukin-6 (IL-6) is the key cytokine mediating age-related inflammation. At the same time, IL-6 has been implicated in the pathophysiology of cardiovascular and renal disorders as a major pro-inflammatory cytokine. Thereby, IL-6 is placed at the intersection between natural and pathophysiological kidney aging, and the latter accelerates systemic aging and substantially limits life quality and expectancy. Growing clinical availability of IL-6 inhibitors for treatment of autoimmune and autoinflammatory disorders demands clarification of potential renal consequences as well. Available data suggests that IL-6 inhibition may be renoprotective in some kidney disorders, but the setting of kidney aging has received only minor attention. The present review focuses on the known effects of IL-6 associated with natural or pathophysiological renal aging.