Podophyllotoxin (PPT) is an active pharmaceutical ingredient (API) with established antitumor potential. However, due to its systemic toxicity, its use is restricted to topical treatment of anogenital warts. Less toxic PPT derivatives (e.g., etoposide and teniposide) are used intravenously as anticancer agents. PPT has been exploited as a scaffold of new potential therapeutic agents; however, fewer studies have been conducted on the parent molecule than on its derivatives. We have undertaken a study of ultrastructural changes induced by PPT on HaCaT keratinocytes. We have also tracked the intracellular localization of PPT using its fluorescent derivative (PPT-FL). Moreover, we performed molecular docking of both PPT and PPT-FL to compare their affinity to various binding sites of tubulin. Using the Presto blue viability assay, we established working concentrations of PPT in HaCaT cells. Subsequently, we have used selected concentrations to determine PPT effects at the ultrastructural level. Dynamics of PPT distribution by confocal microscopy was performed using PPT-FL. Molecular docking calculations were conducted using Glide. PPT induces a time-dependent cytotoxic effect on HaCaT cells. Within 24 h, we observed the elongation of cytoplasmic processes, formation of cytoplasmic vacuoles, progressive ER stress, and shortening of the mitochondrial long axis. After 48 h, we noticed disintegration of the cell membrane, progressive vacuolization, apoptotic/necrotic vesicles, and a change in the cell nucleus’s appearance. PPT-FL was detected within HaCaT cells after ~10 min of incubation and remained within cells in the following measurements. Molecular docking confirmed the formation of a stable complex between tubulin and both PPT and PPT-FL. However, it was formed at different binding sites. PPT is highly toxic to normal human keratinocytes, even at low concentrations. It promptly enters the cells, probably via endocytosis. At lower concentrations, PPT causes disruptions in both ER and mitochondria, while at higher concentrations, it leads to massive vacuolization with subsequent cell death. The novel derivative of PPT, PPT-FL, forms a stable complex with tubulin, and therefore, it is a useful tracker of intracellular PPT binding and trafficking.

Entosis is a form of cell-in-cell interaction observed in epithelial cancers, characterized by the internalization of one cell into another. This process is initiated by cell detachment, cadherin-mediated homotypic adhesion, and the formation of an entotic vacuole. Mechanistically, entosis is driven by Rho/ROCK signaling and actomyosin contractility in the invading (inner) cell, which becomes stiffer and is pulled into the softer host (outer) cell. A functional assay using differently stained cell populations allows for the assessment of pharmacological interventions on either the inner or outer cell during entosis. In this study, we investigated the impact of MEK pathway inhibition on entosis in two epithelial cancer cell lines, BxPC3 (pancreatic cancer) and MCF7 (breast cancer). BxPC3 cells, which rely on adhesion, exhibited a significant reduction in entotic index upon MEK inhibition. In contrast, MCF7 cells showed no selectivity of entosis to three different MEK inhibitors. These findings suggest cell-type-specific regulation of entosis, potentially linked to differences in protrusion formation mechanisms and upstream Ras signaling pathways previously implicated in cancer cell motility.

Introduction: Histamine is a biologically active amine involved in inflammatory, immunological, neurological, and gastrointestinal processes. Impaired degradation of histamine, may lead to histamine intolerance and multisystem symptoms. The low-histamine diet is interesting strategy as a non-pharmacological recommendation for managing histamine-related disorders. Background: There are many disorders which symptoms may be associated with the level of histamine, for instance: chronic spontaneous urticaria, inflammatory bowel disease, recurrent headaches, gastrointestinal manifestations in hypermobile Ehlers–Danlos syndrome, and anaphylaxis-like reactions. Although dietary histamine restriction is frequently recommended, the consistency between online dietary advice and scientific evidence could be misleading. Methods: Scientific articles adressing the use of low-histamine diet were identified through an analysis of databases. Secondly, five publicly accessible websites identified through search phrases related to the low-histamine diet were analyzed. Afterwards, five scientific studies from literature databases were reviewed to compare publicly accessible information to recommendations in scientific articles from literature databases. Key findings: Analyzed articles suggest that impaired histamine degradation can result in multisystem symptoms, which may improve after implication dietary histamine restriction. The analysis of low-histamine diet recommendations revealed inconsistencies between internet-based information and literature from scientific databases. Conclusions: A low-histamine diet may provide clinical benefit in selected patients with histamine-related disorders. However, dietary recommendations are often inconsistent with scientific evidence. Implementation of the diet should be individualized and evidence-based. Further studies could be beneficial to establish clear and standardized dietary guidelines for histamine related conditions.

Background: Chronic kidney disease (CKD) affects approximately 10% of the population and is associated with increased cardiovascular risk and mortality. In advanced stages, protein-energy wasting (PEW) and malnutrition-inflammation complex syndrome (MICS) are common and worsen clinical outcomes. Evidence suggests that nutritional interventions, including modification of protein, sodium, potassium, and phosphorus intake, and selected supplementation, may slow CKD progression and reduce metabolic complications. Aim: This review summarizes current evidence on nutritional interventions and supplementation in CKD, considering disease stage and treatment modality, and identifies gaps requiring further research. Materials and methods: A narrative review of international guidelines (KDIGO, KDOQI, ESPEN) and clinical trials and meta-analyses published between 2009-2026, identified through searches of PubMed, Cochrane Library, Scopus, and Google Scholar, focusing on CKD stages G3-G5. Results: Individualized protein restriction, sodium limitation, and qualitative phosphorus control improve metabolic parameters, blood pressure and albuminuria. Low- and very low-protein diets, particularly with amino acid ketoanalogue supplementation, are associated with slower CKD progression and a delayed initiation of renal replacement therapy. Plant-based diets may additionally improve acid-base balance, phosphate metabolism, and inflammation. The strongest evidence for supplementation concerns vitamin D, iron, and amino acid ketoanalogues, while data on omega-3 fatty acids, probiotics, and B vitamins remain inconclusive. Conclusions: Nutritional management is a key component of CKD care. Individualized dietary strategies and targeted supplementation may provide nephroprotective and metabolic benefits, although further high-quality randomized trials are needed to confirm effects on hard clinical endpoints.

Background:Hearing loss affects roughly 65% of adults aged 70 and older, vision impairment 20–30%, and dual sensory loss becomes more common with age. Meta-analyses show that these forms of sensory decline are associated with higher risks of hypertension, stroke, coronary heart disease, and cardiovascular mortality, even after adjustment for traditional cardiovascular risk factors. Shared vascular pathology explains part of these associations, but psychosocial and communication pathways may also contribute. Aim:To summarize evidence on psychosocial and communication-mediated mechanisms linking sensory decline to cardiovascular risk in older adults and to outline an integrated conceptual model. Material and Methods:A narrative review was conducted using targeted searches of PubMed and Google Scholar. Meta-analyses, cohort studies, and relevant qualitative and mechanistic literature were included. Findings were synthesized qualitatively. Results:Sensory impairment increases cognitive and communicative demands, which may heighten chronic stress and influence neuroendocrine and inflammatory pathways linked to cardiovascular disease. Reduced sensory input limits social participation and contributes to social isolation and loneliness, both established cardiovascular risk factors. In healthcare settings, communication barriers can impair symptom reporting, treatment adherence, and management of complex cardiovascular regimens. These pathways complement biological mechanisms and help explain persistent associations between sensory decline and cardiovascular outcomes. Conclusions:Psychosocial and communication mechanisms appear to be modifiable contributors to cardiovascular vulnerability in older adults with sensory impairment. Potential strategies include routine sensory screening, communication-accessible care, and interventions addressing isolation and stress. Randomized trials are needed to determine whether sensory interventions can reduce cardiovascular events.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in the population of reproductive-age women. Although there is considerable research on gut dysbiosis in PCOS, alterations in the vaginal microbiome are comparatively understudied, despite their possible reproductive implications. The main aim of this review was to summarize current evidence regarding vaginal microbiome composition in women with PCOS and evaluate its associations with relevant clinical parameters. A literature search was performed using PubMed for studies published between January 2015 and November 2025. Eight studies met the inclusion criteria, each examining vaginal microbiome composition in women with PCOS. The most important findings included reduced Lactobacillus dominance, increased alpha-diversity, and enrichment of anaerobic taxa, such as Gardnerella vaginalis, Prevotella, and Ureaplasma species. Current evidence indicates that vaginal dysbiosis is more common among women with PCOS than in healthy controls, though it is not universal. Causal relationships in this field remain unclear, and data on interventions are insufficient. Randomized controlled trials evaluating interventions that target the microbiome and their impact on reproductive outcomes are an important research priority.