Search Results (26,896)

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: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which causes numerous metabolic changes, leading to non-alcoholic fatty liver disease (NAFLD). Our study explored the suggested role of hypoxia-inducible factor 1-α (HIF-1α) in the pathophysiological mechanisms linking OSA with NAFLD. Methods: This case-control study was conducted at the Sleep Disorders Unit at Qena University Hospital from March 2022 to October 2023, including 64 subjects (48 OSA patients; in a secondary analysis, OSA patients were further stratified according to the presence or absence of NAFLD–16 controls) who were subjected to a polysomnography (PSG) for apnea hypopnea index (AHI) and transient elastography for controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM). Serum levels of HIF 1-α, fasting blood glucose, and fasting insulin were measured. Results: HIF-1α level showed the highest significant value was in the severe group (p = 0.001). Additionally, the severe group had the highest LSM compared to the other groups (p = 0.032). OSA patients with NAFLD, compared to OSA patients without NAFLD, showed significantly higher BMI (42.74 vs. 29.11 kg/m², p < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) mean score (3.92 vs. 1.21, p < 0.0001), HIF-1α level (6.01 vs. 2.14 ng/L, p = 0.045), and the LSM score (5.55 vs. 3.85 kPa, p < 0.001). HIF-1α showed significant positive correlations with AHI (r = 0.515, p < 0.001), waist circumference WC (r = 0.291, p = 0.045), HSI (r = 0.3, p = 0.038), and CAP score (r = 0.288, p = 0.047). Conclusions: Although serum HIF-1α levels were significantly higher in OSA patients with NAFLD and correlated with indices of hepatic steatosis, HIF-1α was not identified as an independent predictor of NAFLD after adjustment for metabolic confounders, suggesting a potential role of hypoxia-responsive pathways in pathophysiology of NAFLD in OSA. Full article

Background: Solriamfetol, a dopamine and norepinephrine reuptake inhibitor widely used in narcolepsy management, has not been thoroughly investigated for its anti-fibrotic and anti-inflammatory properties. Herein, we investigated its potential therapeutic applications and underlying mechanisms in both cellular and murine models of pulmonary fibrosis. Methods: To induce fibrosis, C57BL/6 male mice (six-week-old) were administered bleomycin via the intratracheal route. These animals subsequently received solriamfetol orally once per day at dosages of 3 or 10 mg/kg. Histological and immunohistochemical techniques were employed to evaluate inflammatory cell infiltration, collagen accumulation, and α-smooth muscle actin (α-SMA) expression in bronchoalveolar lavage samples and lung tissue sections. Cytokine levels were measured by ELISA, and gene/protein expression of pro-fibrotic markers, A_2A/A_2B adenosine receptors (ARs), adenylate cyclases (ACs), Epac, K_Ca3.1, and adenosine deaminase (ADA) were assessed via quantitative PCR and Western blot. Electrophysiological recordings evaluated K_Ca3.1 channel activity. Purified ADA and normal human lung fibroblasts (NHLFs) were treated with solriamfetol to assess effects on ADA activity and levels of cAMP and adenosine, respectively. Results: Solriamfetol significantly reduced inflammatory cell infiltration, collagen accumulation, and α-SMA expression in fibrotic lungs. Solriamfetol restored downregulated A_2AAR, A_2BAR, ACs, and Epac, while suppressing ADA expression and activity, resulting in elevated extracellular adenosine and intracellular cAMP. The intervention potentiated Epac signaling and inhibited fibroblast activation. Solriamfetol inhibited the K_Ca3.1 current in fibroblasts and reduced K_Ca3.1 protein expression levels in TGFβ-treated fibroblasts and lung tissues from bleomycin-challenged mice. Notably, these effects were abolished by A_2AAR or A_2BAR antagonists, implying that they occur through AR-mediated pathways. Conclusions: Solriamfetol inhibits ADA and reinforces adenosine–cAMP signaling, suppressing pathological fibroblast activation. These findings suggest its therapeutic utility as a novel anti-fibrotic compound for various fibrotic diseases, including pulmonary fibrosis. Full article

RPE65, an isomerohydrolase expressed in retinal pigment epithelium (RPE), is critical for the visual cycle. More than 115 missense variants of the RPE65 gene have been associated with Leber’s congenital amaurosis (LCA), a severe childhood retinal dystrophy. Due to high genetic heterogeneity, the variant-specific pathogenic mechanisms remain largely uncharacterized. In this study we focus on an LCA patient carrying compound heterozygous RPE65 variants (c.200T > G, c.430T > C), aiming to dissect the mechanistic/functional basis of mutated protein-driven retinal degeneration and evaluate gene therapy-mediated restoration using patient-specific hiPSCs-RPE (iRPE). Transient overexpression of wild-type/mutant RPE65 in HEK293T cells showed both variants markedly destabilize the RPE65 protein through the autophagosome–lysosome degradation pathway and its isomerohydrolase activity required for the retinoid visual cycle. We further established a patient-specific iRPE platform suitable for enzymatic activity analysis. Characterization of patient-specific iRPE cells revealed those compound heterozygous variants did not compromise iRPE morphology, most gene expression, or core canonical physiological features of iRPE. However, they significantly downregulate endogenous RPE65 protein abundance and dampen enzymatic function. Subsequently, we delivered RPE65 via adeno-associated viral (AAV) vectors driven by either the ubiquitous CMV promoter or RPE-specific VMD2 promoter into patient iRPE to validate therapeutic potency, and verified that exogenous RPE65 supplementation effectively restores deficient isomerohydrolase activity in this disease model. Collectively, this work elucidates the variant-specific pathogenesis of RPE65-associated LCA and preliminarily assesses the efficacy of gene augmentation, providing preclinical experimental evidence to support the referral of this patient for clinical RPE65 gene replacement therapy. Full article

Doxorubicin (DOX) is a potent chemotherapeutic drug, whose clinical application is largely restricted by dose-dependent cardiotoxicity (DIC). Dracocephalum moldavica L. is a classic medicinal and edible plant with obvious cardiovascular protective effects; however, the role of its total flavonoids (TFDM) in DIC remains unclear. This study explored the cardioprotective effect of TFDM on DOX-induced myocardial injury and its mechanism related to mitochondrial quality control. We established in vivo and in vitro DIC models and adopted echocardiography, detection of cardiac injury and oxidative stress indicators, transmission electron microscopy, mitochondrial functional assessment and Western blotting, with AMPK knockdown performed for mechanism verification. Results showed that TFDM effectively improved cardiac function, reduced myocardial oxidative stress and apoptosis, and maintained mitochondrial ultrastructure and energy metabolism. TFDM activated the AMPK/PGC1α signaling axis to facilitate mitochondrial biogenesis, and AMPK silencing eliminated the protective effect of TFDM. In conclusion, AMPK/PGC-1α pathway is a primary key pathway involved in TFDM’s protective effects, which provides an experimental basis for the development of Dracocephalum moldavica L. as a functional food and adjuvant agent against DIC. Full article

Microplastics are ubiquitous environmental particles with complex physical and chemical properties that enable them to interact with other contaminants. Recent evidence suggests that microplastics act as carriers for various chemical pollutants, altering their transport, deposition, and deposition dose. This conceptual review synthesizes current knowledge of radon progeny behavior and microplastic properties and suggests potential mechanisms for their interaction, although direct experimental validation of radon progeny specifically is currently lacking. It discusses attachment kinetics, transport pathways in air and water, and microplastic-mediated shifts in human lung deposition patterns and ecological exposure. Theoretical dosimetry reasoning suggests that, if attachment occurs, small respirable microplastics (1–10 μm) could increase inhalation doses by prolonging the airborne residence time of progeny indoors, whereas macro- and coarse microplastics would primarily affect localized environmental hotspots. These possibilities remain to be tested experimentally. Integrated experimental and modelling approaches, including radon chamber studies, aerosol and aquatic transport experiments, respiratory tract modelling, and ecological bioassays, are proposed to quantify these processes and inform risk assessment. Knowledge gaps remain in attachment efficiency, retention, co-contaminant interactions, and long-term exposure scenarios. Addressing these gaps is critical for refining human and ecological risk assessments and guiding regulatory frameworks in radon-microplastic-impacted environments. Full article

Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with limited publicly available spatial transcriptomic resources, particularly for extensive-stage disease (ES-SCLC), which remains absent from major initiatives such as The Cancer Genome Atlas (TCGA). To improve accessibility, interoperability, and downstream analytical utility of existing spatial transcriptomic data, SCAPeSCLC was developed as a harmonized dataset derived from two publicly available Gene Expression Omnibus (GEO) series, GSE261345 and GSE261348, generated using the NanoString GeoMx Digital Spatial Profiler platform. The resource integrates normalized expression measurements from 296 tumor regions of interest (ROI) across 58 ES-SCLC patients treated with first-line chemoimmunotherapy. Normalized expression matrices were reformatted into survival-ready column-based datasets at both ROI and patient levels following log₂-transformation and standardization. Clinical metadata were curated and harmonized, and progression-free survival (PFS), disease-specific survival (DSS), overall survival (OS), time-on-treatment (ToT), follow-up intervals, and censoring indicators were reconstructed from the original clinical records. Biological pathway (BP) activity scores were generated using Cancer Transcriptome Atlas (CTA) annotations encompassing 106 BPs. To account for variable ROI sampling across patients, Bayesian hierarchical modeling was applied to estimate patient-level pathway activity, yielding posterior estimates and corresponding credible intervals. The resulting resource includes harmonized expression matrices, pathway enrichment profiles, Bayesian posterior estimates, survival-ready clinical annotations, and standardized Cox proportional hazards modeling outputs, along with a dedicated GitHub repository. SCAPeSCLC is intended to facilitate confirmatory analyses, integrative statistical modeling, methodological benchmarking, and reproducible exploration of spatial transcriptomic determinants of survival in ES-SCLC. Full article

The aim of this systematic literature review was to analyse how hydrological–hydraulic modelling, through the assessment of surface stormwater runoff behaviour, can support the participatory management of socio-environmental risks such as flooding, flash floods, and landslides. For this, 31 publications dating from 2015 to 2025 were selected from Scopus, ScienceDirect and Web of Science databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, to examine the importance of integration between modelling and community participation for risk management. The results indicate that, despite recent advances, most studies still prioritise either the technical application of modelling or community participation, without articulating the two approaches in risk analysis and management processes. There is a scarcity of methods that effectively combine local knowledge into the collaborative construction of scenarios and in the continued use of modelling as a tool for monitoring flood risks to disseminate community information. It was observed that studies carried out in developing countries use simpler methods, using community participation as an alternative to the absence of data. In developed countries, however, studies use more advanced methodologies through institutionalised processes. In contexts marked by high vulnerability, the integration of community participation and technical tools, such as hydrological–hydraulic modelling, represents a promising pathway toward more equitable and efficient risk management practices, aligning with sustainability agendas such as the Sustainable Development Goals (SDGs). Full article

Background: Cervical cancer remains a significant health issue in Indonesia, where structural barriers, fragmented information, and sociocultural norms continue to hinder timely diagnosis and treatment. Families play a central role throughout the illness journey, yet their perspectives are often overlooked in the development of digital patient navigation systems. This study explored family experiences, caregiving challenges, and expectations for a family-centered digital navigation model, DIVA.ID, by integrating Digital Health frameworks and Family Systems Theory. Methods: A qualitative descriptive approach was employed through semi-structured, in-depth interviews with 18 purposively selected family caregivers of women with cervical cancer at a major referral hospital in West Java. Participants were selected because they were directly involved in daily care, treatment decisions, logistical support, or emotional assistance. Interviews were conducted between August and October 2025 and continued until thematic saturation was reached, as indicated by repetition of categories and the absence of new major codes in the final interviews. Data were analyzed using inductive–deductive content analysis guided by Elo and Kyngäs, with five researchers conducting independent coding, iterative code comparison, consensus meetings, and theoretical mapping. Results: Four main themes emerged: (1) family involvement in decision-making, including collective discussion, shifting authority roles, and patient autonomy; (2) caregiver burden, involving physical exhaustion, psychological distress, social restriction, stigma, financial pressure, and employment disruption; (3) psycho-spiritual coping mechanisms, including emotional sharing, prayer, crying, patience, and surrender to God; and (4) digital healthcare needs, covering BPJS guidance, treatment information, scheduling, communication pathways, shelter support, and mental–spiritual support. Mapping these themes to Digital Health frameworks and Family Systems Theory clarified how DIVA.ID could translate family experiences into practical navigation functions. Conclusions: This study provides empirical foundations for a culturally sensitive, family-centered digital navigation model in Indonesia. Rather than demonstrating effectiveness, the findings identify design requirements for DIVA.ID that should be tested in subsequent feasibility, usability, and intervention studies. Full article

Ovine pulmonary adenocarcinoma (OPA), caused by the exogenous Jaagsiekte sheep retrovirus (JSRV), shares several pathological and molecular features with human lung adenocarcinoma, providing an important model for comparative oncology. JSRV pathogenesis is mostly studied at the transcriptome level, with systematic proteomic and metabolomic studies remaining insufficient. Therefore, this study aimed to systematically characterise the molecular alterations associated with JSRV-induced OPA by integrating direct data-independent acquisition proteomics and untargeted metabolomics. We established an OPA model by infecting lambs with JSRV and performed multi-omics analyses on the lesion and control lung tissues (n = 3 per group for both proteomic and metabolomic analyses). In total, 1631 differentially expressed proteins and 748 differential metabolites were identified, and the two omics datasets exhibited highly coordinated variations. Integrated analyses suggested that adhesion remodelling (with downregulated LIMCH1), endoplasmic reticulum stress (with upregulated HYOU1), and metabolic and immune-related alterations (accompanied by elevated GFPT1 and PTGS2) represent major biological processes associated with JSRV infection. Western blot analysis confirmed the expression changes in these proteins. Overall, this study provides a multidimensional molecular landscape of OPA and expands current understanding of the molecular alterations associated with JSRV infection. These findings provide candidate pathways and molecular targets for future mechanistic studies and comparative investigations of lung adenocarcinoma. Full article

Background and Objectives: Angiographic no-reflow (NRF) after percutaneous coronary intervention (PCI) reflects impaired microvascular reperfusion despite successful treatment of the epicardial culprit lesion. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in endothelial signaling, platelet biology, inflammation, and angiogenesis. Its relationship with NRF in non-ST-segment elevation myocardial infarction (NSTEMI) remains insufficiently characterized. Materials and Methods: This single-center prospective observational cohort study included 700 consecutive NSTEMI patients undergoing culprit-lesion PCI. Admission serum total BDNF was measured before PCI using a standardized enzyme-linked immunosorbent assay protocol. Angiographic NRF was defined as final thrombolysis in myocardial infarction (TIMI) flow <3 and/or TIMI 3 flow with myocardial blush grade (MBG) 0–1 in the absence of residual stenosis, dissection, severe spasm, or other mechanical obstruction. Four sequential logistic regression models were used to evaluate the stability of the association between BDNF and NRF: Model 1 adjusted for clinical variables; Model 2 further adjusted for laboratory and inflammatory variables; Model 3 further adjusted for cardiac injury and functional variables; and Model 4 further adjusted for angiographic and procedural variables. Discrimination, calibration, reclassification, decision-curve analysis, and internal validation were assessed. Results: NRF occurred in 114 of 700 patients (16.3%). Serum total BDNF was higher in the NRF group than in the reflow group [555 (465–688) vs. 386 (292–496) pg/mL, p < 0.001]. BDNF remained independently associated with NRF across sequential models: Model 1 OR 1.67 per 100 pg/mL (95% CI 1.43–1.96), Model 2 OR 1.49 (95% CI 1.24–1.79), Model 3 OR 1.41 (95% CI 1.16–1.72), and Model 4 OR 1.31 (95% CI 1.07–1.60). The BDNF-only AUC was 0.787, while the final BDNF-enriched Model 4 reached an AUC of 0.866. The optimism-corrected bootstrap AUC was 0.852 and the 10-fold cross-validated AUC was 0.845. Conclusions: Higher admission serum total BDNF was independently associated with angiographic NRF in NSTEMI patients undergoing PCI and improved risk discrimination when added to clinical, biochemical, cardiac, and angiographic predictors. These findings suggest that serum total BDNF may reflect a context-dependent biomarker signal related to acute thrombo-inflammatory, platelet-associated, and microvascular injury pathways; however, the observed incremental value was modest and requires external validation. Full article

Perillyl alcohol, a rare monoterpenoid, can be widely used in chemical, agriculture, and food industries and shows promise in medicine as an anticancer agent. The artificial synthesis of perillyl alcohol from β-pinene epoxide using inexpensive and abundant turpentine is chosen for improving its pharmaceutical and industrial applications. This work presents a green and sustainable catalytic process for the rearrangement of β-pinene epoxide to perillyl alcohol. A novel ammonium phosphomolybdate solid acid (AC-COIMI-NH₄PMo) was built via phosphomolybdic acid chemisorption onto an N-basylous site of imidazolized activated carbon followed by ammonia fumigation, which exhibits outstanding catalytic performance in the rearrangement of β-pinene epoxide to perillyl alcohol in nitromethane under mild conditions. At 80 °C over 80 min, nearly complete conversion of the epoxide is achieved with a perillyl alcohol selectivity of 77.3%. Moreover, the used catalyst can be readily recycled after washing with hot nitromethane. The favorable proton-donating capacity of nitromethane for the rearrangement and the comparison of adsorption energies between substrates and main products on ammonium phosphomolybdate are revealed through DFT calculation. Kinetic analysis based on the Langmuir adsorption model indicates that the surface reaction of strongly adsorbed β-pinene epoxide is a rate-determining step and follows a zero-order reaction process; the activation energy is 29.64 kJ/mol within the temperature range of 50–80 °C. Finally, a parallel catalytic rearrangement mechanism is proposed, and an eight-step reaction pathway toward perillyl alcohol is elaborated for β-pinene epoxide conversion on AC-COIMI-NH₄PMo. Full article

Calcrete-type uranium prospectivity prediction is challenged by the strong heterogeneity of multi-source geoscientific raster datasets, weak anomaly responses, and the lack of explicit heterogeneous information organization in conventional deep learning models. In this study, the Yilgarn Craton of Western Australia was selected as the study area, and a geology-guided fixed-group fusion ResUNet model (GGF-ResUNet) was developed based on 12-channel multi-source geoscientific raster datasets. At the input stage, the evidence layers were divided into four fixed geoscientific proxy groups according to their data modality and geological interpretation, namely gravity, aeromagnetic, radiometric, and geochemical groups, and intra-group channel weighting together with inter-group gating was introduced to enhance the hierarchical representation and adaptive fusion of heterogeneous information. Ablation results showed that GGF-ResUNet achieved better performance than the baseline ResUNet, with AUC increasing from 0.9340 to 0.9740 and F1-score improving from 0.7264 to 0.8356. Further comparative experiments with Attention U-Net, U-Net, SegNet, and FCN showed that GGF-ResUNet achieved comparatively better quantitative performance and more spatially coherent prediction results under the current experimental setting. Without substantially increasing model complexity, the proposed method improves the representation and integration of heterogeneous geoscientific information and provides a feasible technical pathway for calcrete-type uranium prospectivity prediction under weak-anomaly conditions. Full article

Background: Diabetes mellitus (DM) and chronic kidney disease (CKD) are major contributors to global morbidity and mortality, with disease progression being closely linked to persistent inflammation, oxidative damage, and apoptotic pathways. Icariin (ICA), a bioactive flavonoid compound isolated from Epimedium brevicornum Maxim, has attracted considerable interest because of its diverse pharmacological properties. We evaluated the effect of ICA on streptozotocin (STZ)-induced diabetic rats with or without adenine-induced CKD. This combined model reproduces several key structural and functional characteristics observed in human diabetic kidney disease and advanced CKD. Methods: Male Wistar rats were allocated to five treatment groups and followed for 35 days. Group 1 served as the untreated control and received standard chow; Group 2 was administered streptozotocin (STZ); Group 3 received STZ together with icariin (ICA); Group 4 received a combination of adenine and STZ; and Group 5 was treated with adenine, STZ, and ICA. ICA was administered at a dose of 200 mg/kg by oral gavage. Biochemical, oxidative stress and inflammatory markers were assessed. Results: Rats treated with STZ, with or without adenine, exhibited significant hyperglycemia, elevated plasma levels of cystatin C and indoxyl sulphate, increased urinary levels of N-acetyl-β-D-glucosaminidase (NAG) and NAG/creatinine ratio, and reduced creatinine clearance. Additionally, there were significant decreases in renalase activity and urine osmolality, significant increases in interleukins IL-1β and IL-6 and TNF-alpha levels, and a decrease in IL-10 level. Oxidative stress biomarkers were also significantly impaired in both groups, along with significant renal histopathological changes. ICA significantly ameliorated these alterations in both experimental groups. Conclusion: These findings demonstrate that ICA exerts renoprotective and anti-inflammatory effects in a clinically relevant model of advanced diabetic CKD. Further studies are warranted to elucidate the underlying mechanisms and determine the translational relevance of these findings. Full article

Fiber-reinforced polymer (FRP) composites are extensively used in aerospace, civil engineering, and defense applications because of their low density, high specific strength, corrosion resistance, and structural design flexibility. However, prolonged exposure to hygrothermal conditions, ultraviolet (UV) radiation, and thermo-oxidative environments can progressively damage these materials, leading to mechanical degradation and shortened service life. This review examines environmental aging in FRP composites at the levels of the polymer matrix, fiber/matrix interface, and reinforcing fibers. Representative predictive models, finite element methods, and experimental characterization techniques are summarized, together with the evolution of mechanical properties under different aging conditions. Hygrothermal degradation is mainly associated with moisture diffusion, matrix swelling, and interfacial debonding, whereas UV and thermo-oxidative aging are largely governed by photo-oxidation and thermally activated free-radical reactions. These processes may induce chain scission, crosslinking, matrix embrittlement, and interface damage. Under coupled environmental exposure, degradation is not simply additive because moisture transport, oxidation kinetics, and failure pathways may interact. Future research should emphasize multiscale characterization, anti-aging modification, interface engineering, protective coatings, and reliability-oriented lifetime prediction. Full article