Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a rising global health issue. Chronic intestinal inflammation is an important risk factor for colorectal cancer (CRC). Despite significant progress in IBD and CRC treatment, numerous patients remain resistant to standard pharmacotherapy or experience severe side effects that prevent them from continuing treatment. There is evidence suggesting that bioactive substances in Lentinula edodes have immunomodulatory and anticancer properties. This fungus is currently classified as a functional food, considering its beneficial effects on human health and special nutritional value. Studies conducted in vitro and in animal models demonstrated that L. edodes bioactive compounds, in particular glucans, have anti-inflammatory and antioxidant effects, induce apoptosis of cancer cells, reduce tumor angiogenesis, restore gut microbiome heterogeneity and improve gut barrier dysfunction. Moreover, clinical trials confirmed that these compounds combined with standard chemotherapy have a significant effect in improving the prognosis of CRC patients. In addition, L. edodes glucans increase microbial diversity and enhance interferon (IFN)-γ production by immune cells. Future studies must be focused on understanding the pathways and mechanisms associated with the observed effects. Moreover, both randomized trials and long-term follow-up studies are needed to confirm their effectiveness in the treatment of IBD and CRC.

Osteoarthritis (OA) is a highly prevalent joint disorder traditionally considered a consequence of mechanical cartilage wear; however, it is now recognized as a complex, multifactorial disease driven by interconnected molecular and cellular mechanisms. This narrative review synthesizes current knowledge on key pathogenic pathways underlying OA progression, with a focus on inflammatory signaling, subchondral bone remodeling, and dysregulation of mineral metabolism. Chronic low-grade inflammation promotes catabolic responses in chondrocytes and contributes to cartilage degradation. In addition, obesity influences OA pathogenesis through both biomechanical loading and adipokine-mediated inflammatory mechanisms. Alterations in the receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANK/RANKL/OPG) axis disrupt bone homeostasis and promote pathological subchondral remodeling, while imbalances in inorganic phosphate metabolism contribute to crystal deposition and further joint damage. These processes interact synergistically, driving disease progression. Current therapeutic strategies remain largely symptomatic and do not adequately target underlying molecular drivers. A deeper understanding of these mechanisms may facilitate the development of disease-modifying therapies.

Air pollution impairs mitochondrial biology through mechanisms driven by oxidative stress, excessive reactive oxygen species (ROS) production, apoptosis, and tissue injury. Specific components of air pollution—particularly PM_2.5 and microplastic fibers — disrupt mitochondrial function via multiple interconnected pathways. The study aimed to evaluate the mitochondrial function in bronchial epithelial cells from healthy and asthmatic donors following exposure to PM_2.5 and/or microplastics. Primary bronchial epithelial cells from healthy and asthma groups were cultured in control, lipopolysaccharide (LPS), cigarette smoke extract (CSE), and allergic (house dust mite [HDM] + IL-13)-treated models and stimulated with microplastic fibers and/or PM_2.5 for 24 h. The mitochondrial activity (Seahorse) and ROS production were measured. In healthy cells, 24-h exposure to PM_2.5 increased maximal mitochondrial respiration across all conditions and basal and ATP-dependent production in the CSE-stimulated group, with no signs of exhaustion. In asthma cells, however, ROS production was not matched by increased mitochondrial activity, suggesting impaired adaptive responses. PM_2.5 exposure partially attenuated the increase in maximal respiration induced by allergic stimulation in asthma cells. Microplastic exposure exhibited a distinct pattern: it did not increase ROS, but enhanced mitochondrial metabolism (basal respiration and ATP-dependent respiration) in LPS and CSE, and HDM/IL-13 (maximal respiration and ATP-dependent respiration) treated asthma cells, yet reduced cell viability after 48 h in LPS-treated asthma cells, suggesting early mitochondrial fatigue under this condition. PM_2.5 exposure alters mitochondrial activity via oxidative stress, imposing greater metabolic stress and potential harm to bronchial epithelial cells from individuals with asthma, while exerting lower negative effects on cells from healthy donors. Microplastic exposure had context-dependent effects in asthmatic bronchial epithelial cells.

Dicarboximide derivatives and piperazine-containing compounds have independently demonstrated promising anticancer properties; however, limited studies explored the biological potential of their hybridization. In the present study, six novel aryl- and heteroarylpiperazine derivatives (1–6) were synthesized and evaluated for their antiproliferative activity. The structures of all tested compounds were confirmed by ¹H and ¹³C NMR, as well as ESI–MS spectral analysis. Their cytotoxicity was assessed in vitro against a panel of hematological and solid tumor cell lines, with non-malignant keratinocytes used as the control. Compounds 1–3 displayed the highest anticancer activity, whereas the halogen-substituted derivatives 4–6 were markedly less active, suggesting a structure–activity relationship. The derivative 1 showed the broadest and most potent cytotoxic profile across the tested cancer cell lines. Mechanistic studies demonstrated that the investigated compounds induced distinct biological effects depending on the cell line, including apoptosis induction, necrotic cell death, G₀/G₁ cell-cycle arrest, increased caspase-3/7 activity, and altered NF-κB signaling. Taken together, these findings suggest that subtle structural modifications within dicarboximide–piperazine scaffolds may influence both antiproliferative activity and cellular responses.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by impaired B-cell maturation and poor prognosis in relapsed/refractory (R/R) cases. While CD20-targeted immunotherapies offer clinical benefit, their efficacy is limited by low and heterogeneous CD20 expression on BCP-ALL cells. In this study, we demonstrate that overexpression of wild-type IKZF1, a tumor suppressor frequently mutated in high-risk BCP-ALL, upregulates CD20 and promotes leukemic B cell maturation. Using a transcriptional mimicry approach, we identified mTORC1 inhibitors as compounds showing similarity to selected IKZF1-induced transcriptional signatures, including convergence on B-cell maturation and induction of CD20 expression both in vitro and in vivo. mTORC1 inhibition enhanced the antitumor efficacy of anti-CD20 monoclonal antibodies and promoted B-lineage antigen expression, while downregulating immature markers. Mechanistically, CD20 upregulation was mediated via the AKT–FOXO1 axis, with AKT phosphorylation being essential for this effect. Importantly, this phenotypic shift was observed in BCP-ALL models with IKZF1 deletions, highlighting the relevance to high-risk disease. Our findings support the use of mTORC1 inhibitors to sensitize BCP-ALL cells to CD20-directed immunotherapies and provide a strong rationale for their clinical evaluation as adjuncts to anti-CD20 immunotherapy in BCP-ALL.