BioFactors最新文献

Glioblastoma (GB) is highly malignant with a median survival of 14 months despite conventional treatments like surgery, radiotherapy, and temozolomide. Resistance to these therapies necessitates innovative approaches, such as immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1) to enhance T-cell-mediated tumor destruction. However, clinical trials have shown limited ICI efficacy in GB due to its immunosuppressive microenvironment and the blood–brain tumor barrier (BBTB), which impairs drug delivery. Emerging evidence highlights the gut microbiota as a pivotal modulator of ICI response, enhancing CD8⁺ and CD4⁺ T-cell function, antigen presentation, and immune modulation via the gut-brain axis in cancers. In addition, studies showed that gut-derived metabolites, including short-chain fatty acids, modulate immune responses and support blood–brain barrier integrity by regulating inflammatory signaling and tight junction proteins. Future GB research should prioritize clinical trials, mechanistic studies, and interventional strategies like fecal microbiota transplantation and probiotics to enhance ICI efficacy.

Plant-based food products have been developed from diverse plant sources as new food choices. Fermentation of plant matrices with lactic acid bacteria (LAB) has been shown to improve quality and bioactivity of the resulting product while proteolysis by the LAB in the plant-based matrix remains to be elucidated. In this study, a hazelnut-based matrix prepared for a plant-based product was fermented with four different starter cultures of LAB, and their effects on proteolysis, bioactivity and allergenicity were investigated. Sucrose supplementation of the hazelnut matrix stimulated fermentation and time to reach to the target pH of 4.5 was shortened. CH-1 was the fastest acidifying culture reducing pH to the target value after 5 h. While the cultures RSF-736 and CHN-11 required 18 h for fermentation, R-707 was co-cultured with CH-1 to reach the target pH within the same time. Bacterial counts were in the range of 5–8 log cfu/g without a significant change after 15 days of storage in the hazelnut-based products. Level of proteolysis as measured by changes in soluble protein and total free amino acid contents differed among the cultures. Reductions in the amounts of hazelnut proteins were also confirmed by SDS-PAGE analysis, especially in the products prepared with cultures R-707+CH-1 and RSF-736. Allergenicity of the hazelnut matrix, determined by a hazelnut-specific ELISA test, significantly decreased after fermentation with all the cultures. Fermentation also enhanced total phenolic content and antioxidant activity of the hazelnut matrix with CHN-11 demonstrating the highest values after storage. On the other hand, fermentation did not significantly alter α-amylase inhibitory activity compared to the activity of 10.2% in the unfermented control. In addition, fermentation resulted in no change or a slight reduction in ACE inhibitory activity compared to the activity of 46.9% in the unfermented control depending on the culture. These findings demonstrate that LAB species can degrade hazelnut matrix leading to a reduction in allergenicity and enhancement of antioxidant activity.

Exosomes are nanoscale extracellular vesicles (EVs) that have recently garnered significant attention owing to their crucial role in orchestrating cell-to-cell communication. Through the transfer of heterogeneous molecular cargo encompassing lipids, proteins, cytokines, growth factors, and RNAs (including mRNAs, lncRNAs, miRNAs, and circRNAs), they modulate a wide spectrum of physiological and pathological processes. Exosomes have been extensively investigated as diagnostic tools, therapeutic agents, as well as innovative platforms for drug delivery in metabolic, oncological, cardiovascular, and neurological disorders. Culminating evidence has demonstrated the pivotal role of exosomes in renal pathophysiology. Depending on their cargo content, exosomes represent potential biomarkers for early disease detection and survival prediction across various renal pathologies. While current therapeutic interventions are largely confined to attenuating disease progression, exosomes hold the potential to promote regeneration in both acute kidney injury and chronic kidney diseases. The current review comprehensively examines the clinical utility of exosomal cargo as diagnostic and prognostic biomarkers as well as therapeutic agents in kidney diseases, highlighting their crosstalk with critical signaling pathways implicated in renal pathophysiology. Addressing the current challenges in exosome isolation and standardization, and the development of advanced exosome engineering technologies are crucial for the transformation from experimental research settings to clinical practice. This should be augmented by preclinical validation and well-designed clinical trials, ultimately paving the way for a new era of precision medicine.

Dextromethorphan (DXM), a widely used antitussive agent, was investigated for its effects on mitochondrial F₁F_O-ATPase activity and oxidative phosphorylation. Our results demonstrate that DXM inhibited F₁F_O-ATPase independently of the thiol redox state. Mutual exclusion analysis highlighted an overlapping binding site between DXM and dicyclohexylcarbodiimide (DCCD), indicating a shared or adjacent binding site in the membrane-embedded F_O domain of the enzyme. These findings suggested that DXM selectively targeted the proton translocation mechanism of F₁F_O-ATPase during the ATP hydrolysis and synthesis of ATP. Moreover, kinetic analysis confirmed a high affinity of DXM for the enzyme, with an inhibitory efficiency of 2.37 mM⁻¹⸱s⁻¹. Importantly, DXM did not affect electron transport chain activity but impaired ATP synthesis, as evidenced by altered respiratory control ratios of oxidative phosphorylation. The data obtained offer new insights into its off-target mitochondrial effects and potential implications for bioenergetic regulation.

Tumor suppressor Phosphatase and Tensin Homolog Deleted on Chromosome TEN (PTEN) shows a differential sub-cellular distribution, with its nuclear presence being particularly critical for its multifaceted tumor-suppressive functions. Nuclear PTEN mediates its arsenal of tumor suppressive actions viz., genomic stability maintenance, cell cycle regulation, DNA damage response, and transcriptional modulation, in both phosphatase-dependent and non-phosphatase-dependent manners. Diverse mechanisms exist to facilitate its nuclear import, including passive diffusion, active transport, and post-translational modifications such as monoubiquitination, phosphorylation, and SUMOylation as well as their crosstalk. Similarly, a number of mechanisms dictate the nuclear export of PTEN. Nucleo-cytoplasmic shuttling of PTEN is closely guarded by several protein factors. This review comprehensively explores the proteins involved in the transport and regulation of nuclear PTEN. Furthermore, it highlights the clinical significance of nuclear PTEN levels, which are closely associated with tumor grade, disease prognosis, and patient survival across multiple cancer types. By elucidating these mechanisms, this review underscores the importance of nuclear PTEN in cancer biology and its potential as a therapeutic target.

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. In various types of tumors, ferroptosis is a vital iron-dependent form of regulated cell death. Recent studies suggest that heat shock protein 27 (HSP27), encoded by the heat shock protein family B member 1 (HSPB1) gene, is involved in the regulation of ferroptosis, but the specific mechanism remains unclear. In this study, CSCC cell lines were transfected with lentivirus-mediated HSPB1-shRNA or lentivirus carrying overexpressed HSPB1. CSCC cell lines, xenograft mouse models, and ferroptosis inhibitors or inducers were applied to verify the mechanism and function of HSP27. Downregulation of HSP27 inhibited the proliferation, migration, and invasion of CSCC cells, whereas upregulation of HSP27 showed the opposite results. Similarly, tumor volume and weight were reduced after HSP27 was downregulated in vivo. Further studies revealed that HSP27 promoted the growth of CSCC cells and tumors by inhibiting ferroptosis, and the downregulation of HSP27 enhanced ferroptosis induced by Erastin. Ferrostatin-1 or Erastin successfully reversed the phenotype triggered by HSP27 alterations. HSP27 can induce the growth of CSCC by inhibiting ferroptosis, and is expected to become a new target for the treatment of CSCC.