Search Results (6,718)

Diabetes mellitus is a serious public health problem, mainly due to the difficulty in healing chronic wounds, which present an inflammatory response for long periods of time and are more vulnerable to infections. Hydrogels are a promising therapeutic solution due to their biocompatibility, biodegradability, and ability to allow controlled release of therapeutic agents. The addition of bioactive glasses doped with therapeutic ions to hydrogels can also provide specific biological responses to the system and thus improve tissue regeneration. In this study, a hydrogel based on carboxymethylcellulose and polyethylene glycol with different degrees of crosslinking and enriched with 10% by weight of CeO₂-doped Bioglass 45S5 was developed. Structural, morphological, mechanical, and biological characterizations were performed on bioactive glass, hydrogels, and hydrogels enriched with bioactive glass. Structural analyses confirmed the preservation of the typical amorphous structure of Bioglass 45S5, even after the incorporation of 5% molar CeO₂, as well as the effectiveness of the polymer matrix crosslinking process. Structural analyses demonstrated the preservation of the typical amorphous structure of Bioglass 45S5, even after the incorporation of 5 mol% CeO₂, as well as the effectiveness of the polymer matrix cross-linking process. The hydrogels exhibited distinct behaviours in terms of water absorption and degradation, showing that the sample with the lowest concentration of crosslinkers and bioactive glass allowed for a higher expansion rate and a higher degradation rate. The hydrogel with 10 wt% BG did not compromise cell viability and showed structural integrity after being subjected to cyclic flexible deformations, indicating its safety and suitability for use in tissue engineering. Full article

Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects on eye health. This work provides an overview of selected bioactive substances, such as carotenoids (β-carotene), flavonoids, vitamins C and E, and phytochemicals derived from plants. These agents exhibit antioxidative, anti-inflammatory, antimicrobial, and regenerative properties that may support ocular surface integrity, reduce oxidative damage, and improve visual performance. The integration of such natural remedies into ocular health strategies may offer complementary benefits to conventional therapies. Full article

Bovine endometritis negatively impairs fertility and milk production. Taurine maintains cellular integrity and exerts anti-inflammatory and antioxidant effects. However, whether taurine can treat endometritis remains unclear. This study aimed to investigate taurine’s effect on endometritis and explore its mechanism in vivo. Endometritis models were established in mice via intrauterine lipopolysaccharide (LPS) infusion, followed by 25, 50, and 100 mg/kg taurine treatment. Taurine attenuated inflammation by mitigating histopathological damage, suppressing uterine serum cytokine levels, and preserving tight-junction integrity. It ameliorated oxidative stress by reducing malondialdehyde content, restoring antioxidant activities, and recovering levels of oxidative-stress-related proteins. Apoptosis was alleviated by diminishing the apoptosis ratio and normalizing apoptosis-related proteins. 16S analysis revealed taurine restored uterine microbiota composition by reversing the changes in the abundances of Firmicutes, Bacteroidetes, Nocardioides, Ruminococcus, and Acidibacter. The abundances of Muribacter and Rodentibacter were positively correlated with inflammation. The abundances of Akkermansia and Streptococcus were negatively correlated with inflammation. RNA sequencing showed that the differentially expressed genes were mainly related to immunity. Phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathways were indicated as pivotal mechanisms for taurine’s therapeutic efficacy against endometritis with transcriptomic profiling analysis. This study confirms that taurine alleviates LPS-induced endometritis in mice by modulating PI3K–AKT, MAPK, and NF-κB signaling pathways, indicating its potential as a therapeutic agent for bovine endometritis. Full article

Background: Patients with type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) face elevated risk of hepatobiliary complications. The biliary safety of GLP-1 and dual GLP-1/GIP receptor agonists in this population is uncertain. Methods: We conducted a retrospective cohort study using the TrinetX LIVE global health research network. Adults (≥18 years) with coexisting T2DM and IBD were assigned to exposure (semaglutide or tirzepatide) or comparator (no GLP-1/GIP therapy) cohorts. The index was first prescription (or matched date). Primary outcomes—cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis—were identified by ICD-10 codes. Propensity score matching (1:1 greedy nearest neighbor; caliper 0.1 SD) balanced demographics, comorbidities, GI surgeries, and antidiabetic medications. Results: After propensity score matching, 32,052 patients were included (16,026 per cohort), achieving excellent covariate balance with standardized mean differences < 0.1 for nearly all variables. GLP-1/GIP agonist use was associated with significantly lower risks of multiple biliary complications. Cholelithiasis occurred in 3.5% of GLP-1/GIP users compared with 6.3% of nonusers (risk ratio [RR] 1.81, 95% CI 1.64–2.00; hazard ratio [HR] 1.27, 95% CI 1.14–1.41; p < 0.001). Cholecystitis similarly occurred less frequently among users (0.8% vs. 2.2%; RR 2.74, 95% CI 2.24–3.34; HR 1.85, 95% CI 1.50–2.27; p < 0.001). Choledocholithiasis was also reduced in the GLP-1/GIP cohort (0.6% vs. 1.5%; RR 2.72, 95% CI 2.14–3.46; HR 1.90, 95% CI 1.48–2.44; p < 0.001). Cholangitis events were rare in both groups (0.1% vs. 0.2%) with no significant difference on survival analysis (HR 1.07, 95% CI 0.58–1.97; p = 0.08). Conclusions: In adults with T2DM and IBD, GLP-1 and dual GLP-1/GIP receptor agonists are associated with substantially reduced risks of gallstone-related complications. These real-world data support the gastrointestinal safety of GLP-1–based therapy in a high-risk population and suggest possible biliary protective effects warranting prospective, agent-specific studies. Full article

Brain aging is a progressive process marked by cellular dysfunction, chronic inflammation, and increased susceptibility to neurodegenerative diseases. A growing body of evidence identifies cellular senescence, the accumulation of non-dividing, metabolically active cells with a pro-inflammatory secretory profile (SASP), as a key contributor to cognitive decline and brain aging. This review explores the emerging field of senotherapeutics, which includes senolytics (agents that eliminate senescent cells) and senomorphics (agents that suppress SASP without killing cells), as potential strategies to manage brain aging. We summarize recent preclinical studies demonstrating that senotherapeutics can reduce neuro-inflammation, improve synaptic plasticity, and enhance cognitive function in aged animal models. Additionally, we highlight early-phase clinical trials investigating senolytic compounds in Alzheimer’s disease and discuss key challenges, including the delivery of drugs to the brain, biomarker development, and long-term safety. The review concludes that senotherapeutics, particularly when combined with personalized and multimodal approaches, represent a promising avenue for mitigating age-related cognitive decline and promoting healthy brain aging. Full article

Background/Objectives: Plaque psoriasis is a chronic immune-mediated inflammatory disease affecting approximately 3% of the global population and resulting in a significant deterioration in quality of life. Systemic therapy with monoclonal antibodies (mAbs) targeting TNF-α, IL-23, and IL-17 improves clinical outcomes and patients’ quality of life. Treatment strategies commonly include different mAbs and different sequencing approaches between agents, which are well-established in clinical practice. In contrast, evidence supporting the switch from intravenous to subcutaneous administration of the same mAb remains limited. Herein, we report data from a retrospective case series of patients with plaque psoriasis treated with intravenous infliximab (IV-IFX; Anti TNF-α) and transitioned to subcutaneous infliximab (SC-IFX) to compare clinical and patient-reported outcomes across routes. Methods: A total of 11 plaque psoriasis patients were retrospectively analyzed. The scores of the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician Global Assessment (PGA) were assessed during IV-IFX and after switching to SC-IFX. To evaluate patients’ satisfaction, the Score of Treatment Satisfaction Questionnaire Medication-9 (TSQM-9) was evaluated. Both Student’s t-test and ANOVA were used to assess statistically significant differences between the two routes of administration (p < 0.05). Results: Scores for PASI, DLQI, and PGA were lower with SC-IFX compared with IV-IFX, indicating improved disease control and quality of life after the switch. PASI and DLQI improved in 81% and 100% of patients treated with SC-IFX, respectively. TSQM-9 total scores increased significantly by 24% (p < 0.001). In particular, the questions addressing the “convenience” of treatment revealed a marked advantage for the SC-IFX formulation (p < 0.001). No treatment-emergent adverse events were registered. Conclusions: In this retrospective case series, switching from IV-IFX to SC-IFX appeared to be safe and to maintain or improve clinical response and enhanced treatment satisfaction. These findings highlight the potential of SC-IFX as a viable maintenance option for patients with plaque psoriasis previously treated with IV-IFX. Full article

Background/Objective: Electromagnetic radiation (EMR) from wireless technologies has raised concerns about male reproductive health. We aimed to evaluate the protective role of alpha-lipoic acid (ALA), a potent antioxidant, against testicular alterations induced by 2.45 GHz EMR. Methods: Twenty-eight adult male rats were randomly divided into four groups: control, EMR, ALA, and ALA+EMR. Animals in the EMR and ALA+EMR groups were exposed to EMR for 2 h/day for 1 month. Testicular tissues were examined histologically, stereologically, and immunohistochemically, while serum samples were analysed biochemically. Results: EMR exposure caused marked structural damage, including disruption of seminiferous tubule architecture, increased collagen deposition, and expansion of tubular and interstitial volumes. These pathological changes were primarily prevented in the ALA+EMR group. Immunohistochemical analyses revealed increased IL-6 and TNF-α expression following EMR exposure, whereas ALA supplementation significantly reduced these inflammatory markers and restored AR, ZO-1, and ZO-2 expression. Biochemically, EMR reduced antioxidant enzyme activities (SOD, GSH, GPx) and elevated MDA levels, indicating oxidative stress; these parameters were reversed by ALA treatment. Conclusions: Collectively, our findings demonstrate that 2.45 GHz EMR induces oxidative stress, inflammation, and testicular injury, while ALA provides significant protection. These results highlight the therapeutic potential of ALA as a protective agent against EMR-related reproductive toxicity and infertility risk. Full article

Background/Objectives: Cardiovascular diseases continue to be the foremost global cause of morbidity and mortality, representing about 40% of all causes of death. Atherosclerotic cardiovascular disease is the most common and clinically important type of these, occurring when cholesterol accumulates over time in the artery intima, which induces an inflammatory process that leads to the production of atherosclerotic plaques. Nowadays, lipid profile alterations and high/very high cardiovascular risk can be observed in more and more patients. Combination therapy, which includes high-intensity statins, ezetimibe, bempedoic acid, and PCSK9-targeted medicines, can lower LDL-C by more than 80%, which is far more than the 50% that statin monotherapy usually achieves. Thus, novel lipid-lowering therapies are needed, as current agents—though effective in reducing cardiovascular events—leave considerable residual risk in many patients. Methods: The aim of our study was to evaluate the cost-effectiveness of Inclisiran and its association with standard of care for the prevention of cardiovascular events across multiple international settings, in articles that reported quality-adjusted life years gained and cost-effectiveness metrics. Results: Our findings suggest that the cost-effectiveness of Inclisiran is highly context-dependent, shaped by local pricing, population risk, and system-level capacity. While Inclisiran demonstrates potential economic value in high-income settings or among high-risk patients, its widespread adoption for primary prevention appears unjustified under current conditions. Conclusions: Policymakers should consider risk-based targeting, price renegotiation, and performance-based reimbursement models to improve the value proposition of such interventions. Full article

Type 2 diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance and pancreatic β-cell dysfunction, posing a substantial global health challenge. This review systematically summarizes the therapeutic potential of berberine, a natural isoquinoline alkaloid, in the management of T2DM. Berberine’s pharmacological activities are discussed from multiple perspectives, including enhancing insulin sensitivity and regulating glucose metabolism—encompassing glycogen synthesis, gluconeogenesis, and glucose transport. The review also highlights berberine’s anti-inflammatory, antioxidant, and epigenetic enzyme-targeting actions and its involvement in key T2DM-related signaling pathways such as AKT, AMPK, and GLUTs. These findings collectively elucidate the multi-targeted and multi-pathway molecular mechanisms underlying berberine’s efficacy against T2DM. Additionally, the review covers the pharmacological activities and molecular mechanisms of berberine in treating T2DM complications—including diabetic nephropathy, retinopathy, cardiomyopathy, neuropathy, and diabetic foot ulcers—as well as its clinical and preclinical applications and the synergistic benefits of combination therapy with agents such as metformin, ginsenoside Rb1, and probiotics. By systematically reviewing the literature retrieved from PubMed and Web of Science up to 2025, this article provides a comprehensive summary of current research, offering a theoretical foundation for the clinical use of berberine in T2DM therapy. Full article

Hypoxic–ischaemic encephalopathy (HIE) is a major cause of neonatal brain injury and is associated with a high rate of death and lifelong disability. Its pathogenesis is still poorly understood, and there is no proven treatment for preterm infants. Therapeutic hypothermia for term and near-term infants partially improves outcomes, highlighting the need to target additional mechanisms. This review evaluates evidence that necrosis and necroptosis contribute materially to evolving brain injury in both term and preterm brains. Serial imaging studies suggest that lesions typically develop over many days after birth for term infants and over many weeks after birth for preterm infants. Growing evidence from animal studies shows that severe white matter injury can be mediated by programmed necroptosis. In particular, lesions that evolve late after acute HI are characterised by necrosis in association with agglomerations of microglia, with little apoptotic cell death. Critically, preclinical studies in large and small animals show that outcomes can be dramatically improved by very delayed intervention after HI including with cell therapy, anti-inflammatory agents, and endogenous neurotrophins. These findings strongly support the hypothesis that there may be a window of therapeutic opportunity for days or even weeks after birth to prevent delayed necrotic lesions. Full article

Background/Objectives: Neuroinflammation is a leading factor in secondary brain damage following a traumatic brain injury (TBI). Existing therapeutic approaches have limited efficacy against neuroinflammation. The bone marrow, the primary hematopoietic organ, is also a source of inflammatory cells. We propose that targeting the sympathetic regulation of inflammatory cell mobilization could reduce neuroinflammation after TBI. Methods: In ICR mice, we investigated the immune cell response in the blood, bone marrow, motor cortex, and the subventricular zone after TBI modeling and treatment with the sympatholytic agent reserpine. Results: TBI induced neutrophilia and lymphocytosis in the peripheral blood, activated hematopoiesis in the bone marrow, and triggered neuroinflammation and degenerative changes in the cerebral cortex (CC) and the subventricular zone (SVZ) of mice. Reserpine reduced leukocytosis in the blood and hematopoietic activity in the bone marrow of mice with TBI compared to untreated TBI mice. Furthermore, reserpine decreased neutrophilic and lymphocytic infiltration, as well as the number of Iba1⁺ microglial cells, including M1-polarized microglia, Caspase-3⁺ cells, and cells expressing myeloperoxidase (MPO) in the CC and SVZ of treated mice. The activity of degenerative processes was also reduced. Additionally, reserpine reduced the number of M2-polarized microglial cells in the SVZ. Conclusions: The sympatholytic drug reserpine may hold promise for the development of a novel approach to treating neuroinflammation and degeneration following a TBI. This is based on its ability to reduce hematopoiesis and mobilize inflammatory cells from the bone marrow into the bloodstream. Full article

Senna petersiana (Bolle) Lock is a chemically diverse plant widely recognized for its ethnomedicinal applications across various traditional medical systems. It is native to and widely distributed in African countries, including Ethiopia, Cameroon, and South Africa. This review integrates the phytochemical composition, biological activities, and toxicological effects of S. petersiana. Phytochemical analyses reveal the presence of numerous classes of compounds, including alkaloids, flavonoids, phenolics, anthraquinones, chromones, and sterol glycosides, with variations in concentration across different plant parts. Quantitative studies highlight particularly high levels of phenolics and flavonoids in ethanol, methanol, and acetone extracts, correlating these with enhanced biological activities. Pharmacological investigations demonstrate a spectrum of activities, including antibacterial, antioxidant, anti-inflammatory, antiviral, anthelmintic, and anticancer effects, supporting many of the plant’s traditional uses. Toxicological assessments suggest relative safety at moderate doses, though further evaluation is necessary for specific cell types and high-dose exposures. Despite the promising bioactivities, the mechanisms of action and in vivo efficacy of isolated compounds remain underexplored. Future research should focus on bioassay-guided isolation, detailed pharmacodynamic studies, and comprehensive toxicological profiling to validate and harness the therapeutic potential of S. petersiana. This review highlights the plant’s biochemical complexity and paves the way for its development as a valuable phytopharmaceutical agent. Full article

Cancer therapy resistance emerges from highly integrated molecular systems that enable tumor cells to evade cell death and survive cytotoxic therapeutic stress. High Mobility Group Box 1 (HMGB1) is increasingly gaining recognition as a central coordinator of these resistance programs. This review delineates how HMGB1 functions as a molecular switch that dynamically redistributes between cellular compartments in response to stress, with each localization enabling a distinct layer of resistance. In the nucleus, HMGB1 enhances chromatin accessibility and facilitates the recruitment of DNA repair machinery, strengthening resistance to radio- and chemotherapeutic damage. Cytosolic HMGB1 drives pro-survival autophagy, maintains redox stability, and modulates multiple regulated cell death pathways, including apoptosis, ferroptosis, and necroptosis, thereby predominantly shifting cell-fate decisions toward survival under therapeutic pressure. Once released into the extracellular space, HMGB1 acts as a damage-associated molecular pattern (DAMP) that activates key pro-survival and inflammatory signaling pathways, establishing microenvironmental circuits that reinforce malignant progression and therapy escape. HMGB1 further intensifies resistance through upregulation of multidrug resistance transporters, amplifying drug efflux. Together, these compartmentalized functions position HMGB1 as a central node in the networks of cancer therapy resistance. Emerging HMGB1-targeted agents, ranging from peptides and small molecules to receptor antagonists and nanoformulations, show promise in reversing resistance, but clinical translation will require precise, context- and redox-informed HMGB1 targeting to overcome multifactorial resistance program in refractory cancers. Full article

Background/Objectives: Respiratory tract infections (RTIs) remain a leading cause of morbidity worldwide and are frequently associated with the emergence of multidrug-resistant pathogens. In this context, natural compounds represent a valuable source of novel antimicrobial and immunomodulatory agents. The present study aimed to evaluate the antibacterial, anti-inflammatory, and antioxidant activities of Protegol, a natural food supplement enriched in bioactive phytochemicals including hydroalcoholic extracts of propolis and hedge mustard (Sisymbrium officinale (L.) Scop.) aerial parts, together with honey, against clinically relevant bacterial strains and in cellular models of inflammation and oxidative stress. Furthermore, the ability of the multi-herbal formulation to alter the permeability of the bacterial cell wall was assessed. Methods: The antibacterial properties of Protegol were evaluated by determining its minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) against a panel of Gram-positive and Gram-negative bacteria, using the broth microdilution method. Cell wall permeability was investigated through the propidium iodide (PI) uptake assay. The anti-inflammatory potential was investigated in LPS-stimulated RAW 264.7 macrophages by measuring nitric oxide (NO) production with the Griess assay. The antioxidant activity was evaluated in BALB/3T3 fibroblasts exposed to hydrogen peroxide, using the DCFH-DA assay. Results: Protegol exhibited a broad-spectrum antibacterial effect, with MIC values ranging from 1.5 to 6.2 mg/mL and MBC values between 3.1 and 12.4 mg/mL. The strongest activity was observed against Staphylococcus aureus and Streptococcus pyogenes, including clinical isolates, while moderate efficacy was detected against resistant Klebsiella pneumoniae strains. PI uptake assays confirmed a dose-dependent disruption of bacterial membrane integrity, supporting a direct effect of Protegol on cell wall permeability. In macrophages, Protegol significantly and dose-dependently reduced NO release, lowering production to 44% at the highest concentration tested. In BALB/3T3 cells, Protegol markedly decreased ROS accumulation to 24% at the same concentration. Conclusions: Overall, the findings support the potential of Protegol as a natural adjuvant to the conventional therapies for respiratory tract health by counteracting bacterial pathogens, reducing inflammation, and mitigating oxidative stress, thereby supporting host defense mechanisms in the context of respiratory tract infections. Full article

Mesenchymal stromal cells (MSCs) are promising therapeutic agents, largely due to their capacity for self-renewal, differentiation, and immunomodulation. Importantly, these beneficial effects are frequently mediated by the MSC secretome, which contains factors with anti-inflammatory, anti-apoptotic, and pro-regenerative properties. However, cellular senescence can impair these critical functions. To identify senescence-associated changes in the MSC secretome that may regulate aging and intercellular communication, we performed a mass spectrometry-based proteomic analysis of the conditioned medium from MSCs undergoing stress-induced senescence. Our analysis confirmed the upregulation of established aging markers, such as IL-6, PAI-1, and IGFBP7. Furthermore, we identified a significant increase in lesser-known senescence-associated secretory phenotype (SASP) components, including INHBA—a known inhibitor of proliferation—and DKK3, which blocks stromal cell pluripotency. Pathway analysis revealed that stress-induced senescence broadly affected proteins involved in glycolysis, immune response, hemostasis, and the regulation of cell death and the cell cycle. These alterations are likely to negatively impact the MSC microenvironment. Interestingly, the cellular response to senescence was dualistic. Alongside detrimental SASP factors, we observed an increase in protective proteins such as annexins (ANXA1, ANXA2), antioxidants (TXN, PRDX1, PRDX6), and the heat shock protein HSPB1, which collectively defend neighboring cells from inflammation and oxidative stress. These findings underscore the complex etiology of cellular senescence and the paradoxical nature of the SASP. The obtained data also emphasize the necessity of comprehensive proteomic profiling of the MSC secretome across different aging models to harness the full therapeutic potential of MSCs and their secretomes for regenerative medicine. Full article