Search Results (5,766)

The aim of this review is to provide a narrative analysis of the role of Lactobacillus acidophilus as an active modulating factor in the prevention and treatment of cancer and allergic diseases. The paper discusses the molecular, metabolic, and bionanotechnological mechanisms of Lactobacillus acidophilus’s anticancer and immunomodulatory effects, which define this probiotic as an essential component of modern natural and functional medicine. A narrative review of the scientific literature was conducted, mainly from 2019–2026, focusing on the results of in vitro studies and studies on preclinical in vivo models, which analyzed the effect of live L. acidophilus strains, tyndallized bacteria (paraprobiotics) and cell-free supernatant from L. acidophilus cultures on, among others, immune system signaling pathways, tissue cytokine profile, and the integrity of the gastrointestinal epithelial cell barrier (enterocytes). Results indicate that L. acidophilus exerts significant antiallergic, antiproliferative, and proapoptotic effects against many types of cancer. Among other aspects, the ability of L. acidophilus to stimulate the production of anticancer exopolysaccharides and short-chain fatty acids, which directly influence the functioning of immune cells, is covered. The article thoroughly explains the immunomodulatory effects of L. acidophilus and the ability of this probiotic to regulate cytokine profiles, which helps promote an anti-inflammatory environment crucial for maintaining intestinal homeostasis. The article also discusses the direct interaction of L. acidophilus with immune cells, such as dendritic cells and macrophages, which leads to their activation and subsequent influence on the differentiation of T lymphocytes, which play a key role in the regulation of immune processes and in the development of immune tolerance. L. acidophilus is a universal mediator of immunological and metabolic homeostasis. Its ability to synergize with conventional therapies (chemotherapy, oncolytic virotherapy) and its innovative applications in the creation of postbiotics and paraprobiotics may provide a new approach to the treatment of inflammatory, allergic, and neoplastic diseases. Further clinical studies are necessary to assess the efficacy, safety, and optimal dose of this probiotic, which are essential for the widespread use of L. acidophilus in human therapy. Full article

Background: To investigate the protective effects of Phellodendron amurense Rupr. polysaccharides (PAP), alkaloids, and flavonoids in alleviating diabetic kidney disease (DKD) and to elucidate the role of the PI3K/AKT/GSK-3β/Nrf2 signaling pathway. Methods: Active components were extracted and quantified. In vitro, high-glucose (HG)-induced human kidney-2 (HK-2) cells were used to screen the optimal fraction via CCK-8, reactive oxygen species (ROS), TdT-mediated dUTP Nick-End Labeling (TUNEL), and Western Blot (WB) assays. In vivo, a DKD rat model was established using 2% Streptozotocin (STZ) and a high-fat with high-sugar diet. Rats were treated with PAP and LY294002. Renal damage and signaling pathway proteins were evaluated using histological staining and WB. Results: Among the tested components, PAP conferred the most pronounced cytoprotection against HG-induced injury in HK-2 cells. PAP significantly reduced glomerular damage, collagen deposition, and glycogen accumulation in the kidneys of DKD rats. Mechanistically, PAP activated the PI3K/AKT/GSK-3β/Nrf2 pathway, upregulating HO-1 and NQO1, while inhibiting the TGF-β1/Smad2 pathway and Bcl-2/Bax-mediated apoptosis. These protective effects were significantly attenuated by LY294002. Conclusions: Among the tested fractions under the present experimental conditions, PAP exhibited the most pronounced protective activity. These protective effects were partially mediated through the PI3K/AKT/GSK-3β/Nrf2 pathway, which enhanced antioxidant capacity while reducing fibrosis and apoptosis. Full article

Background: Olfactory dysfunction is a pathology associated with viral infections, toxic damage, aging, and neurodegenerative diseases. Damage to the olfactory epithelium impairs olfactory function and related neurological behaviors. This study evaluated the restorative effects of Scutellaria baicalensis Georgi (SBG) extract and baicalein in a methimazole-induced olfactory dysfunction model. Methods: Olfactory epithelial damage was induced in mice with methimazole, followed by treatment with SBG extract or baicalein. Olfactory and neurobehavioral functions were assessed using odor-finding, novel object recognition (NOR), Morris water maze (MWM), open field (OFT), and elevated plus maze tests (EPM). Histological, immunohistochemical, and in vitro analyses were performed to evaluate epithelial regeneration, mature olfactory sensory neurons (OSNs) expressing olfactory marker protein (OMP), and proliferative activity. Results: Methimazole induced severe olfactory epithelial damage, impairing olfactory behavior and reducing learning and memory. Treatment with SBG extract and baicalein significantly improved olfactory and cognitive functions. Histological and immunohistochemical analyses confirmed restoration of epithelial structure and olfactory neurons. In vitro, SBG extract increased epithelial cell density and modulated proliferative activity. Conclusions: SBG extract and baicalein promote recovery of olfactory function and improve neurobehavioral outcomes, indicating their potential as therapies for olfactory dysfunction. Full article

Background/Objectives: Myocardial microcirculatory dysfunction is a critical pathological feature of cardiovascular diseases, closely associated with inflammation, oxidative stress, and excessive neutrophil activation. Neutrophil extracellular traps (NETs) serve as crucial mediators of myocardial microvascular inflammatory injury. Dalbergia odorifera volatile oil (DOVO) demonstrates anti-inflammatory and antioxidant properties; however, its protective role against myocardial microcirculatory damage and its regulatory effect on NET formation remain inadequately characterized. This study investigates the protective effects of DOVO on myocardial microcirculatory disturbances and elucidates the underlying mechanisms related to NETs. Methods: A rat model of myocardial microcirculatory dysfunction was established through polyethylene microsphere injection, and an in vitro neutrophil inflammation model was generated using differentiated HL-60 cells. DOVO was administered at various doses both in vivo and in vitro, and hemodynamics, inflammatory cytokines, oxidative stress, and NET-related markers, including MPO and CitH3, were analyzed. Results: DOVO dose-dependently ameliorated microcirculatory impairment, hemodynamic disorders, inflammation, and oxidative stress in rats, significantly suppressing NET formation. In differentiated HL-60 cells, DOVO similarly reduced inflammatory gene expression and inhibited LPS-induced NETs production by downregulating MPO and CitH3. Conclusions: DOVO suggests a protective effect against myocardial microcirculatory injury by inhibiting oxidative stress, inflammatory responses, and subsequent NET formation. These findings elucidate a novel mechanism by which DOVO alleviates microcirculation-related cardiac damage and provide a theoretical basis for its application in cardiovascular injury. Full article

Growth hormone-releasing hormone (GHRH) antagonists have displayed anti-neoplastic activity against a multitude of cancers in vitro, as well as in vivo, via xenografted tumors in nude mice. Following a successful demonstration of GHRH antagonists treating non-Hodgkin’s lymphoma and the discovery of GHRH mRNA and peptide products in immune cells, GHRH antagonism was explored in acute myeloid leukemia (AML), a disease characterized by a malignant expansion of immature myeloid progenitors, and poor 5-year survival. Targeted therapies have yielded breakthroughs in treatment response and overall survival, such as all-trans retinoic acid/arsenic trioxide (ATRA/ATO) for acute promyelocytic leukemia (APL), or FLT3 inhibitors, IDH inhibitors, and menin inhibitors for AML harboring actionable genetic lesions. However, therapeutic resistance remains a major barrier to durable remission. GHRH receptor (GHRH-R) has been reported in several experimental models of AML, including drug-resistant sublines. Significant time- and dose-dependent reduction in leukemic growth was observed in vitro and in vivo following MIA-602 treatment. FLT3 inhibitor resistance has been associated with activation of PI3K/AKT, ERK/MAPK, inflammatory, stromal, and apoptotic escape pathways. The documented effects of GHRH-R antagonism raise the possibility that it could influence signaling networks relevant to therapeutic resistance in AML. This hypothesis remains speculative; to date no studies have stratified AML by FLT3 status in the context of GHRH-R expression or GHRH antagonism, and there is currently no evidence that MIA-602 directly alters FLT3 receptor signaling or inhibitor sensitivity. Full article

Background/Objectives: Glucocorticoids, including dexamethasone (DEX), are known to demonstrate anti-inflammatory activity, suppress steroidogenesis, and mitigate the adverse effects of chemotherapy. They are therefore widely employed for managing solid malignancies. Emerging evidence indicates that DEX modulates both systemic and local renin–angiotensin system (RAS) activity, including genomic signaling via the glucocorticoid receptor (GR). Methods: DEX-dependent transcriptional responses for the angiotensin receptor genes (AGTR1, AGTR2, MAS1, and LNPEP) were evaluated in ovarian (SKOV3, KURAMOCHI) and prostate (DU-145, PC3) cancer cell lines. The cells were cultured under different serum conditions to determine the influence of nutrient availability on tumor progression. Results: DEX demonstrated distinct mechanisms of action between the ovarian and prostate cancer models. It was found to promote cancer cell survival through tissue-specific modulation of metabolic activity, clonogenic capacity, cell cycle distribution, and apoptotic responses. These effects were accompanied by condition-dependent alterations in angiotensin receptor gene expression. Hence, DEX may mediate the remodeling of local RAS signaling, which may be significant in overall survival and disease-free survival. The findings also indicate a previously-unreported NR3C1–LNPEP correlation, which was consistently observed across in vitro systems and patient datasets, in both ovarian- and prostate-derived cancer models. Conclusions: DEX appears to exert context-dependent regulation of RAS-associated gene networks in ovarian and prostate cancer, suggesting a role in tumor adaptive responses and potentially in therapeutic contexts. Full article

Reparative macrophage polarization and macrophage-derived reactive oxygen species (ROS) are required for ischemia-induced revascularization in peripheral artery disease (PAD). Our previous study showed that mitochondrial fission protein dynamin-related protein 1 (DRP1) promotes reparative polarization and metabolic reprogramming in macrophages and post-ischemic neovascularization. However, the redox-dependent mechanism governing DRP1 activation in this context remains elusive. Here, using a mouse hindlimb ischemia (HLI) model of PAD, we identify cysteine sulfenylation (CysOH) of DRP1 as a critical redox modification induced in ischemic bone marrow (BM)-derived cells. BM chimeric mice reconstituted with CRISPR/Cas9-generated “redox-dead” DRP1-C631A knock-in mutant (Drp1^C/A) BM exhibited markedly reduced limb perfusion recovery and CD31⁺ capillary density in ischemic muscles following HLI. These defects were associated with enhanced Ly6G⁺ neutrophil accumulation, pro-inflammatory F4/80⁺CD80⁺ M1-like macrophages and reduced anti-inflammatory F4/80⁺CD206⁺ M2-like macrophages in ischemic muscle. Mechanistically, using an in vitro PAD model, hypoxia serum starvation (HSS) rapidly induced NADPH oxidase 2-dependent cytosolic ROS production and DRP1-CysOH formation in wild-type macrophages. In contrast, Drp1^C/A macrophages failed to undergo DRP1-CysOH-dependent mitochondrial fission under HSS, resulting in aberrant metabolic reprogramming characterized by enhanced glycolysis and mitochondrial ROS, pro-inflammatory p-NF-κB and M1-genes, and suppressed anti-inflammatory p-AMPK, efferocytosis and M2-genes. Thus, our findings establish DRP1 sulfenylation as a previously unrecognized redox-sensing mechanism that links ischemia-induced ROS to reparative macrophage reprogramming and revascularization, identifying a novel therapeutic target for PAD. Full article

Orchid plants, due to their high aesthetic qualities of large inflorescences, long flowering period, and ease of care, have high commercial potential; however, when grown industrially in factories, they are susceptible to infectious diseases. In this study, we isolated from Phalaenopsis spp. plants epiphytic, rhizospheric, and endophytic bacteria associated with soft rot symptoms. Twenty-nine isolates exhibiting pectolytic activity were identified as strains of the genera Bacillus, Klebsiella, Microbacterium, Paenibacillus, Paracidovorax, Pseudomonas, and Psychrobacillus based on 16S rRNA analysis. These isolates were tested for their ability to produce cellulase, amylase, sucrase, proteinase, and lipase; to form biofilms; and to exhibit motility (swimming and swarming). Potato microplants under in vitro conditions were used as a model object for initial screening of the strains’ potential phytotoxicity. Most strains were shown to inhibit plant growth, particularly root development. Injection of suspensions of these strains into orchid leaves caused symptoms of soft rot. Thus, we isolated Gram-positive bacteria for the first time from orchid tissues with soft rot symptoms and demonstrated an association of these strains with plant tissue maceration in potato and orchids. Gram-positive bacteria with pectolytic activity are not typical pathogens of orchid soft rot and may require changes in approaches to the monitoring of phytopathogens for this group of plants. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide (LIR), are widely used in humans to treat type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease. In mammals, GLP-1 RAs have been shown to influence hepatic lipid metabolism, although the underlying mechanisms remain unclear. In fish, GLP-1 also plays an important role in regulating hepatic processes, including glycogenolysis, gluconeogenesis, and lipolysis. However, the effects of GLP-1 RAs on liver lipid metabolism in fish remain largely unexplored. Objective: This study aimed to evaluate the effects of LIR on lipid target genes using primary hepatocytes from brown trout as an in vitro model. Methodology: After 24 h, a hepatocyte monolayer culture was established, and cells were exposed for 24 and 48 h to supplemented L-15 medium (control), 0.1% dimethyl sulfoxide in supplemented L-15 medium (solvent control), and five single exposures to LIR at 1, 10, 100, 500, and 1000 nM. After 24 and 48 h, cell viability was assessed using the trypan blue exclusion assay. Gene expression was analysed by real-time qPCR, targeting genes involved in lipogenesis, lipid transport, and cholesterol efflux. Results: No concentration-dependent effects on cell viability were observed. Gene expression analysis showed that LIR exposure modulated the mRNA levels of lipid-related genes, including acetyl-CoA carboxylase (ACC), acyl-CoA long-chain synthetase 1 (Acsl1), and fatty acid synthase (FAS), with time being the main influencing factor. Overall, expression levels were higher at 48 h compared to 24 h. Additionally, dose-dependent effects were observed for ACC expression, with higher LIR concentrations showing significant differences compared to controls. Conclusions: These findings indicate that LIR modulates lipid-related gene expression in primary hepatocytes of brown trout without affecting cell viability. The results suggest that GLP-1 receptor activation may influence key pathways involved in hepatic lipid metabolism, with time-dependent effects playing a predominant role. Overall, this study supports the use of brown trout primary hepatocytes as a suitable in vitro model for investigating hepatic lipid responses to LIR and other GLP-1 receptor agonists, while providing initial insight into their potential effects in fish. Full article

Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer’s disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a transitional stage between normal aging and the onset of dementia, is thought to represent an early phase of this pathological continuum. Studies at the cellular level suggest that the conditions impair the maintenance of established neuronal processes/networks and restrict their capacity for elongation or re-elongation. They may also attenuate the activation and process extension of quiescent neural progenitor or stem-like cells. These early cellular changes precede overt neurodegeneration in neural tissue and are likely to contribute to cognitive decline. They highlight the importance of in vitro models for identifying molecular targets involved in recovery from disease. In this study, we investigated the effects of aggregated Aβ (25–35) on neuronal process elongation and associated intracellular events in the N1E-115 cell line, a widely used model of neuronal differentiation. Addition of aggregated Aβ to cultured N1E-115 cells attenuated process elongation in a concentration-dependent manner. This morphological impairment was accompanied by decreased expression of neuronal differentiation markers. In contrast, at the half-maximal inhibitory concentration for process elongation, long-term cultured cells did not exhibit apparent process retraction or degenerative morphology. This mild but progressive impairment, without extensive cell death, is consistent with the cellular features of early-stage conditions rather than advanced Alzheimer’s pathologies. Similar results were observed in primary cortical neurons. Aβ also decreased the level of GTP-bound Ras and phosphorylation of the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). Furthermore, treatment with hesperetin, a bioactive flavonoid compound, recovered the Aβ-induced inhibition of neuronal process elongation. Hesperetin also restored Ras and MAPK/ERK states, suggesting that its effects are associated, at least in part, with modulation of signaling through Ras and MAPK/ERK. Our findings suggest that hesperetin may serve as a useful molecular probe for modulating early cellular responses associated with Alzheimer’s disease-related pathology. This in vitro model might serve as a useful platform for investigating the molecular target candidates involved in recovery from nervous system disorders. Full article

Amyotrophic lateral sclerosis (ALS) remains an intractable motor neuron (MN) disease with a growing patient population and few effective treatments. Here, we review how extracellular phosphoglycerate kinase 1 (ePgk1) improves neurite outgrowth of MNs (NOMN) and axonal growth, both in vitro and in vivo. Our group first elucidated a novel non-canonical function of ePgk1 as a cross-tissue mediator between nerve and muscle tissues. We then discovered that neural membranous Enolase 2 (Eno2) serves as a receptor of ligand ePgk1 and that ePgk1-Eno2 interaction suppresses the Rac1-GTP/p-Pak1-T423/p-P38-T180/pMK2-T334/p-Limk1-S323 axis, reducing p-Cofilin and promoting NOMN and axonal growth, finally suggesting that the 419th aspartic acid residue of Eno2 mediates this interaction. In a crucial preclinical step, we truncated two short 16-amino-acid derivatives from Pgk1, FD-1/-2, each mediating neuroprotection comparable to that of full-length 417-amino-acid Pgk1 in ALS animal models, in terms of improvements of innervated neuromuscular junction, MN cell bodies, motor performance, and endpoint prolongation. In this context, we also discuss the opposite function driven by Eno1-plasminogen interaction and by Eno2-ePgk1 interaction; the latter results in unfavorable for tumorigenesis. Unlike intracellular Pgk1 roles, ePgk1 is an extracellular factor with anti-angiogenic properties, further positioning ePgk1 and its FD-1/-2 as promising protein/peptide drugs for ALS treatment. Full article

Background/Objectives: The microbiota–gut–brain axis (MGBA) plays a pivotal role in cognitive function, making psychobiotics a promising strategy for managing neurodegenerative diseases. Lactic acid bacteria (LAB) from traditional fermented foods represent a valuable source of candidate strains, and multi-strain consortia may offer enhanced therapeutic efficacy through synergistic effects. This study evaluated the functional and psychobiotic potential of three lactic acid bacteria (LAB) strains isolated from fermented foods, assessed as monocultures and a multi-strain consortium (MIX). Methods: The research encompassed an initial screening of the individual strains and the MIX, assessing their adhesion to mucin, stability in a static in vitro digestion model, and amino acid profiling. Subsequently, the LAB MIX underwent long-term evaluation in a dynamic gastrointestinal model (SHIME^®) inoculated with microbiota from a patient with Alzheimer’s disease, during which alterations in gut microbiota composition and amino acid metabolism were analyzed. Results: The LAB MIX demonstrated high stability under digestive stress and effective mucoadhesive properties. Furthermore, the consortium demonstrated a distinct metabolic signature, driving enhanced functional effects that complemented or exceeded those observed in individual monocultures. In the SHIME^® model, the MIX induced significant, site-specific shifts in microbial composition, notably increasing lactobacilli abundance. These taxonomic changes correlated with an enriched metabolic profile, including elevated levels of GABA precursors and amino acids with antioxidant potential, which are crucial for MGBA modulation. Conclusions: These results identify the LAB consortium as a compelling psychobiotic candidate. Further in-depth in vivo and clinical studies are required to validate its therapeutic potential for MGBA modulation. Full article

Cytomegalovirus (CMV) is a major determinant of post-transplant morbidity in solid organ transplant recipients, not only through direct viral disease but also through a broad spectrum of indirect effects that may adversely influence graft and patient outcomes. This review summarizes current clinical and mechanistic evidence regarding the mechanisms of CMV-associated indirect injury in transplantation, drawing on human observational studies together with supporting in vitro and animal-model data. CMV establishes lifelong latency with intermittent reactivation and exerts sustained immunomodulatory effects on both innate and adaptive immunity, which may persist even during low-level viral replication. The mechanisms discussed include monocyte reprogramming, altered antigen presentation, T-cell and natural killer cell dysregulation, endothelial activation and dysfunction, chronic inflammatory signaling, impaired antimicrobial defense, and disturbances in metabolic regulation. The review considers how these mechanisms have been proposed to translate into major post-transplant complications, including acute rejection, chronic allograft dysfunction, cardiovascular and thrombotic disease, post-transplant diabetes, and increased susceptibility to secondary bacterial, fungal, and viral infections. It also addresses current preventive strategies, although evidence regarding their effectiveness in reducing indirect clinical outcomes remains limited and largely observational. Much of the supporting evidence is associative, and the contribution of CMV is often difficult to separate from that of the overall immunosuppressive burden and the comorbidities of transplant recipients. With these considerations, the available evidence supports regarding CMV not merely as an opportunistic pathogen, but as a persistent immunobiological driver of long-term transplant injury. Improved understanding of these indirect effects may enhance risk stratification, support biomarker-guided prevention, and inform future strategies aimed at reducing long-term graft dysfunction and patient morbidity after transplantation. Full article

Fucoidan, a sulfated polysaccharide, is known for its beneficial bioactive effects, for example antioxidant, anti-inflammatory, and vascular modulatory effects. Such a bioactive compound may also be useful for treating neurodegenerative diseases like age-related macular degeneration (AMD). Our research focuses on AMD-related pathomechanisms using primary porcine retinal pigment epithelium (RPE) cells in vitro and zebrafish (Danio rerio) models in vivo. We tested the bioactivity of a commercially available fucoidan (FVs) from bladderwrack with regard to pathomechanisms of AMD. We performed multiplex assays, RT-qPCR and fluorescence-based assays for the formation of nitric oxide (DAF-FM assay) and reactive oxygen species (DCF-DA assay) to analyze angiogenesis-related chemokines and pro-inflammatory cytokines as well as protection against oxidative stress and inflammatory insult. Our results showed that FVs significantly reduced the secretion of pro-angiogenic vascular endothelial growth factor A (VEGF-A) and follistatin as well as the pro-inflammatory cytokines interleukin 8 (IL-8) after lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC) induction. Interleukin 6 (IL-6) was also reduced in the supernatant of the RPE cells. Additionally, in zebrafish, fucoidan decreased the production of NO and ROS. Gene expression of zebrafish embryos revealed anti-inflammatory effects by suppressing pro-inflammatory genes and significantly downregulating, e.g., interleukin 1 beta (IL-1β). These findings indicate modulation of oxidative stress, inflammatory responses, and VEGF secretion of the used FVs. This study demonstrates that fucoidan possesses AMD-relevant bioactivities in vitro and in vivo, suggesting fucoidan warrants further investigation in AMD-related research and related pathological mechanisms. Full article

Orthoebolavirus causes severe Ebola virus disease (EVD) and deadly outbreaks in humans. This infection occurs through macropinocytosis and trafficking to late endosomes or lysosomes that utilize the receptor Niemann–Pick C1 (NPC1) to enter the cell cytoplasm. We designed peptide inhibitors based on the NPC1 receptor to target the NPC1 binding site to block viral entry. The results indicated that the ligand-based peptide inhibitors showed potent inhibition activities in vitro studies against pseudotyped or replication-competent Orthoebolavirus. Therefore, we further evaluated one of them in a mouse model challenged with mice-adapted Ebola viruses, which showed some protection efficacy compared with the control group. This study suggests that ligand-based peptides are encouraging inhibitors in the development of inhibitors against Ebola virus infection. Full article