Search Results (11,305)

The escalating challenge of antimicrobial resistance has spurred interest in probiotics as alternatives for combating bacterial infections. This study aimed to isolate and characterize probiotic Lactobacillus johnsonii (L. johnsonii) from yak feces with protective efficacy against acute Escherichia coli (E. coli) infection. In vitro, DY2 supernatant inhibited the growth of E. coli. In vivo, mice pretreated orally with DY2 (1 × 10⁹ CFU/mL) for 21 days before E. coli challenge exhibited significantly reduced weight loss (p < 0.001), lower bacterial translocation in the intestines (p < 0.001), and normalized organ indices (p < 0.05) compared to untreated infected controls. DY2 modulated host immune and oxidative responses by significantly lowering serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6; p < 0.001 to p < 0.05) and malondialdehyde (MDA; p < 0.001), while elevating levels of the anti-inflammatory IL-10 (p < 0.05) and antioxidant enzymes (SOD, GSH-Px, T-AOC; p < 0.001 to p < 0.01). Histologically, DY2 preserved intestinal mucosal integrity, with reduced villus shortening and inflammatory infiltration (p < 0.001 for villus length in key segments). 16S rRNA sequencing of intestinal microbiota revealed enhanced α-diversity (p < 0.05 to p < 0.001), community stability, and enrichment of beneficial genera such as Butyricimonas in DY2-treated mice. Conclusively, Lactobacillus johnsonii DY2 protects against acute E. coli infection via anti-inflammatory, antioxidant, gut barrier strengthening, and microbiota-modulating activities. Yak-derived lactobacilli are promising probiotics with excellent antibacterial properties. Full article

Cardiovascular diseases (CVDs) and Alzheimer’s disease (AD) are among the most prevalent chronic conditions, contributing significantly to global morbidity and healthcare burdens. These diseases are increasingly recognized as interconnected through shared mechanisms such as vascular dysfunction, oxidative stress, hypertension, and systemic inflammation, collectively referred to as the CVD-AD axis. Although therapeutic strategies exist for each condition, integrated approaches targeting these common pathways remain limited. This review highlights marine-derived bioactive peptides (BAPs) as multifunctional, sustainable agents for the simultaneous prevention of CVD and AD. It summarizes recent advances in their production, purification, and characterization, with emphasis on enzymatic hydrolysis and separation techniques. Marine BAPs exhibit diverse bioactivities, antioxidant, anti-inflammatory, lipid-lowering, antihypertensive, and neuroprotective, addressing key pathological mechanisms of the CVD-AD axis. Their small size, stability, and favorable safety profile support absorption and initial bioavailability, while sustainable sourcing from underutilized marine biomass enables eco-friendly production. Despite their potential, barriers to scalable production, product standardization, and regulatory approval remain; however, incremental advances are being made toward overcoming these issues. Together with these advances, marine BAPs remain promising candidates for functional foods and nutraceuticals, providing integrated preventive strategies for age-related diseases and supporting long-term cardiovascular and cognitive health. Full article

This review examines how distinct gut microbial community configurations—characterized by differential enrichment of Bacteroides, Prevotella, Ruminococcus, Bifidobacterium, and Lachnospira—may be associated with variations in host redox homeostasis through microbiota-derived metabolites, including short-chain fatty acids, secondary bile acids, and tryptophan derivatives. These compositional patterns represent reproducible features across populations and correlate with differential disease susceptibility in metabolic disorders. While microbial communities exist along compositional continua rather than discrete clusters, stratification based on dominant patterns offers a pragmatic framework for interpreting large-scale microbiome datasets and guiding precision nutrition interventions. Observational evidence suggests Bacteroides-enriched communities may associate with pro-inflammatory signatures, whereas Prevotella- Ruminococcus, Proteobacteria, Bifidobacterium, and Lachnospira-enriched configurations may exhibit anti-inflammatory or antioxidant characteristics in certain populations. However, inter-population variability and species- and strain-level heterogeneity limit generalization. Condition-dependent effects are exemplified by Prevotella copri, which demonstrates pro-inflammatory responses in specific settings despite beneficial profiles in others. When dysbiosis compromises intestinal barrier integrity, microbial translocation may amplify chronic oxidative stress and immune activation. We evaluate therapeutic potential of beneficial genera including Lactobacillus and Bifidobacterium while examining the dose-dependent, context-specific, and sometimes paradoxical effects of key metabolites. Microbiota-stratified therapeutic strategies—personalizing dietary, probiotic, or prebiotic interventions to baseline community composition—show promise but remain at proof-of-concept stage. Current evidence derives predominantly from cross-sectional and preclinical studies; prospective interventional trials linking community stratification with oxidative stress biomarkers remain scarce. The community–redox relationships presented constitute a hypothesis-generating framework supported by mechanistic plausibility and observational associations, rather than established causal pathways. Future research should prioritize intervention studies assessing whether aligning therapeutic approaches with baseline microbial configurations improves outcomes in oxidative stress-related metabolic disorders. Full article

Taurine is a free amino acid with various effects, such as developing the nervous system, an immune function, an antioxidative effect, enhancing muscle and cardiovascular function, and reducing fatigue. In this study, we investigated the effect of taurine supplementation on ischemic neuronal damage in the hippocampus of gerbils. Taurine (150 mg/kg) was orally administered to gerbils before and after induction of transient ischemia. Histologically, we examined surviving and degenerating neurons by neuronal nuclei immunostaining and fluoro-jade C (FJC) staining. Gliosis was morphologically confirmed by GFAP and Iba1 immunostaining. Compared to the ischemia and pre-treated gerbils, pre- and post-taurine supplementation was neuroprotective by maintaining higher number of mature NeuN-immunoreactive neurons and reducing neuronal death (FJC-stained cells) in the hippocampal CA1 region. Additionally, the ischemia-induced reactive astrocytosis and microgliosis was significantly mitigated by long-term taurine treatment in the gerbil hippocampus. Furthermore, we confirmed that pre- and post-taurine supplementation downregulated ischemia-mediated induction in the MAPK cascade, such as ERK, JNK, and p38, which are involved in oxidative stress, inflammation, apoptosis, and cell differentiation, and this treatment upregulated an ischemia-mediated reduction in antioxidants such as SOD2, GPX4, and anti-apoptotic factor Bcl-2 in the gerbil hippocampus. Pre- and post-taurine supplementation also downregulated again the ischemic injury-mediated activation of transcriptional factor NFkβ, an important gene expression regulator, especially in the inflammatory response, and pro-apoptotic factor Bax in the gerbil hippocampus. Our present results suggest that pre- and post-taurine supplementation has potential in neuroprotection against ischemia-induced neuronal death and glial activation by attenuating oxidative stress and apoptosis. Full article

Background/Objectives: UVB radiation triggers oxidative stress, inflammation and extracellular matrix (ECM) remodeling in dermal fibroblasts, contributing to skin aging and fibrosis. Plant-derived extracts with antioxidant and anti-inflammatory activity may counteract these effects. This study evaluated the protective role of Damor Triticum vulgare Aqueous Extract (DTVE) in human dermal fibroblasts (HDFs) exposed to UVB. Methods: Primary HDFs were irradiated with UVB (1.50 J/m²) and treated with DTVE either after irradiation (post-ir) or before and after irradiation (pre-ir). Cell viability was assessed by Trypan Blue and MTT assays. Inflammatory cytokines, fibrosis-related genes, p21 expression, mitochondrial ROS (MitoSOX) and αSMA accumulation were quantified by qRT-PCR, ELISA and immunofluorescence. Results: DTVE was not cytotoxic and preserved HDF viability under UVB exposure. UVB significantly increased pro-inflammatory cytokines, profibrotic markers, αSMA, mitochondrial ROS and p21. DTVE reduced all these UVB-induced alterations, with the pre-ir regimen providing the strongest protection. The extract attenuated early inflammatory activation, limited fibroblast-to-myofibroblast transition and decreased mitochondrial oxidative stress while reducing p21 upregulation. Conclusions: DTVE exerts protective antioxidant, anti-inflammatory and antifibrotic effects in UVB-exposed fibroblasts, particularly when used as pretreatment. These findings support DTVE as a promising candidate to mitigate UVB-induced dermal damage and warrant further investigation for potential therapeutic and cosmetic applications. Full article

Excessive fluoride exposure induces developmental neurotoxicity, but effective preventive strategies are currently scarce. Melatonin (Mel), a lipophilic hormone secreted by the pineal gland, exerts antioxidant, anti-inflammatory, and neuroprotective properties. This study aimed to explore Mel’s protective effect and mechanism against fluoride-induced developmental brain injury. We employed a network pharmacology approach to screen the common targets of Mel and fluoride-induced brain injury and performed enrichment analysis. A total of 189 common targets were identified, and these targets were mainly enriched in the HIF-1 signaling pathway and oxidative stress-related pathways. In vivo, Sprague Dawley rats were subjected to perinatal sodium fluoride (NaF) exposure with/without Mel; in vitro, HT22 cells were subjected to NaF and/or Mel. The results showed that Mel improved cognitive impairments and alleviated structural damage to hippocampal neurons and mitochondria. Furthermore, Mel upregulated SIRT3 and downregulated HIF-1α, thereby restoring mitochondrial oxidative phosphorylation and ATP content. This study demonstrates that Mel alleviates fluoride-induced developmental neurotoxicity by improving mitochondrial function through regulating the SIRT3/HIF-1α signaling pathway. This not only offers a novel perspective for elucidating the underlying molecular mechanisms of fluoride-induced developmental neurotoxicity but also provides a theoretical foundation for Mel as a potential protective candidate against fluoride exposure. Full article

Marine ecosystems represent a largely untapped reservoir of bioactive compounds with significant pharmacological potential. This study aimed to evaluate the therapeutic properties of ethanol extracts from four marine species: Padina australis, Spatoglossum asperum, Holothuria (Halodeima) atra, and Hypnea valentiae. Phytochemical screening, along with a comprehensive series of in vitro, in vivo, and in silico assays, was performed to evaluate the extracts’ pharmacological activities, including antioxidant potential (2,2-diphenyl-1-picrylhydrazyl assay), anti-inflammatory effect (carrageenan-induced paw edema method), analgesic activity (acetic acid-induced writhing and tail immersion tests), and anti-arthritic efficacy (protein denaturation assay). The extracts were found to be rich in flavonoids, tannins, alkaloids, saponins, glycosides, and phenolic compounds, which may underlie the observed bioactivities. In the acetic acid–induced writhing test, Hypnea valentiae at 400 mg/kg exhibited the highest peripheral analgesic activity, producing 82.51% inhibition of writhing (p < 0.001). In the tail immersion assay, Padina australis at doses of 200 and 400 mg/kg showed significant central analgesic effects, as evidenced by increased latency time and percentage of maximum possible effect (MPE). In the carrageenan-induced paw edema model, several treatment groups, including Padina australis, Hypnea valentiae, Spatoglossum asperum, and Holothuria atra, at both tested doses showed marked suppression of inflammation, with some groups achieving complete inhibition (100%; p < 0.001) at 120 min. The ethanol extract of Holothuria atra exhibited the strongest antioxidant and anti-arthritic activities, with an IC₅₀ value of 88.39 µg/mL in the DPPH assay and 81.35% inhibition of protein denaturation. Additionally, the compounds derived from the four marine species exhibited significant binding affinity to the selected target receptors, thereby validating the experimental findings. The marine species studied possess multifaceted pharmacological properties, supporting their potential as natural sources for developing therapeutic agents supporting the blue economy. Further studies are recommended to isolate active compounds and elucidate underlying mechanisms to support future drug development efforts. Full article

(1) Background: Chemotherapy-induced hematological toxicity remains a major limitation to treatment continuity. Docetaxel is widely used in solid tumors due to its clinical efficacy, despite cumulative bone marrow suppression and splenic alterations. Curcuma longa is a phytochemical with antioxidant and anti-inflammatory properties that may confer cytoprotective effects on hematopoietic tissues. (2) Methods: One hundred and five male Wistar rats were randomly allocated into five treatment groups and evaluated at 7, 14, and 21 days. Animals received placebo, docetaxel alone, or docetaxel combined with Curcuma longa at doses of 25, 50, or 500 mg/kg/day. Post-treatment hematological parameters and relative spleen weight were analyzed using one-way ANOVA and Tukey’s post hoc test. (3) Results: Docetaxel induced progressive reductions in red blood cell count, hemoglobin, hematocrit, leukocytes, and platelets, with greater severity at day 21. Curcuma longa co-treatment partially mitigated these alterations in a dose- and time-dependent manner. Intermediate doses (25–50 mg/kg) showed the most consistent hematoprotective effects. High-dose treatment (500 mg/kg) was associated with no statistically significant change in relative spleen weight. (4) Conclusions: Curcuma longa partially mitigated docetaxel-induced hematological toxicity and modulated splenic responses in this experimental model. These findings support further translational studies on chemotherapy-induced hematological toxicity to clarify the role of Curcuma longa as a low-toxicity strategy. Full article

The blood–brain barrier (BBB) is a structure that regulates the exchange of substances between the peripheral circulation and the central nervous system (CNS), thereby protecting this environment. An increase in BBB permeability may lead to the influx of inflammatory cells, resulting in neuroinflammation and neurodegeneration. The integrity of the BBB is maintained due to the specific properties of brain endothelial cells. Considering the importance of brain endothelial cells in the BBB during inflammatory processes, these cells may be a target for anti-inflammatory agents. Polyphenols are substances exhibiting the ability to decrease inflammation; therefore, in our research, we aimed to examine their effectiveness in a brain endothelial cell culture stimulated with the pro-inflammatory cytokine TNF-α. The tested polyphenols were myricetin, chrysin, resveratrol, and curcumin. ELISA tests revealed that myricetin and chrysin decreased the concentrations of the pro-inflammatory cytokines IL-1ß, IL-6, and IL-8 secreted by brain endothelial cells. The results of flow cytometry indicate that chrysin and resveratrol are the most potent in downregulating the expression of VCAM-1 on the surface of brain endothelial cells. The obtained results confirm the anti-inflammatory potential of polyphenols in brain endothelial cells. The selected polyphenols also contribute to increasing brain endothelial cell viability and act as antioxidants. Full article

Chlorella vulgaris is a microalga with well-established nutritional, antioxidant, anti-inflammatory, and antibacterial potential. The current study aimed to explore the green synthesis of silver nanoparticles (AgNPs) using the ethanolic extract of C. vulgaris and to assess how nanoparticle formation affects the chemical composition, antimicrobial potential, antioxidant capacity, and spasmolytic activity of the extract, building on earlier evidence for its modulatory effects on gastrointestinal smooth muscle. Even though AgNPs from Chlorella have been obtained previously, to the best of our knowledge, their spasmolytic activity has not been evaluated. To assess their properties and stability, ATR-FTIR, TEM images, XRD, DLS, and zeta potential were used. The obtained AgNPs were mostly spherical (with a diameter between 10 and 50 nm) and showed good colloidal stability. The synthesis of AgNPs resulted in significant changes in lipid composition, pigment content, and fatty acid profiles, including a decrease in total chlorophylls and an increase in mono- and polyunsaturated fatty acids. The biosynthesized AgNPs showed moderate to strong antibacterial activity against a variety of Gram-positive and Gram-negative bacteria, yeasts, and fungi. The most pronounced inhibitory effect was observed against A. niger and P. chrysogenum. In ex vivo organ bath experiments, AgNPs modulated the contractile activity and the spasmolytic profile of isolated rat gastric smooth muscle compared with C. vulgaris extract. These results demonstrate that green-synthesized AgNPs present systems with altered smooth muscle activity and improved antibacterial qualities, underscoring their potential for use in functional foods, nutraceuticals, and gastrointestinal therapeutics. Full article

Background/Objectives: Skin-related disorders such as melanoma, premature aging, and chronic wounds significantly impact individuals’ quality of life and psychological well-being. Melanoma, due to its high metastatic potential and poor response to conventional chemotherapeutic agents, remains a major clinical challenge. Additionally, skin aging and impaired wound healing continue to drive the demand for novel therapeutic strategies and bioactive formulations. Methods: In this study, cinnamic acid (CA), a naturally occurring compound with known anti-inflammatory and antioxidant properties, was incorporated into biocompatible Fmoc-FF dipeptide-based nanogels to improve its stability and therapeutic efficacy. The antitumor effects of CA and CA-loaded nanogels were evaluated using human melanoma (SK-MEL-30) cells, while wound healing activity was assessed on human keratinocyte (HaCaT) cells. Results: The results demonstrated that CA exhibited significant activity against melanoma cells and promoted wound healing, with enhanced effects observed when delivered via Fmoc-FF nanogels. Conclusions: These findings suggest that CA-loaded peptide nanogels represent a promising platform for multifunctional treatment approaches targeting various skin disorders. Full article

Clinoptilolite is a zeolite with a microporous structure that enables ion exchange, molecular sieving, and adsorption, conferring detoxifying, antioxidant, and anti-inflammatory properties. These properties have applications in food, medicine, catalysis, and environmental remediation. This study evaluated the safety of the lab-made Clinoptilolite as a potential food ingredient through a 90-day repeated-dose toxicity study in male and female Sprague Dawley rats. The test substance was administered via oral gavage at doses of 0, 5, 10, and 15 mg/kg bw/day, followed by a 28-day recovery period. In addition, genotoxicity was assessed using the Ames test, in vitro chromosomal aberration assay, and an in vivo micronucleus test. All studies were conducted in accordance with OECD and FDA guidelines. Results showed no adverse systemic, genotoxic, or irreversible effects at any dose, with minor clinical variations being incidental and reversible. Genotoxicity tests confirmed no mutagenic or clastogenic potential. Overall, the lab-made Clinoptilolite evaluated in this investigation was well tolerated, non-toxic, and showed no evidence of treatment-related toxicity at the doses tested. These findings provide supportive evidence for its consideration toward a Generally Recognized as Safe (GRAS) determination. Full article

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, often resulting in multiorgan dysfunction. Among affected systems, the gastrointestinal tract plays a central role in sepsis progression by promoting systemic inflammation through impaired barrier function, immune imbalance, and microbiome alterations. Recent research has identified selected medical gases and gasotransmitters as promising therapeutic candidates for preserving gut integrity in sepsis. In particular, hydrogen, carbon monoxide, and hydrogen sulfide exhibit antioxidative, anti-inflammatory, and cytoprotective properties. These gases act through defined molecular pathways, including activation of Nrf2, inhibition of NF-κB, and preservation of tight junction integrity, thereby supporting intestinal barrier function. In addition, they influence immune cell phenotypes and autophagy, with indirect effects on the gut microbiome. Although most supporting evidence derives from preclinical models, translational findings and emerging safety data highlight the potential of gut-targeted gas-based strategies. This review summarizes current mechanistic and translational evidence for gut-protective medical gases in sepsis and discusses their integration into future organ-specific and mechanism-based therapeutic approaches. Full article

Deregulated Nlrp3 (NOD-like receptor pyrin 3) inflammasome activation is strongly associated with age-related blinding diseases, including cataract. Previously, we demonstrated that loss of peroxiredoxin6 (Prdx6) promotes reactive oxygen species (ROS) amplification and aberrant activation of Klf9 and Nlrp3 inflammasome activity–driven pyroptosis. In this study, using aging mouse(m)/human(h) lenses and lens epithelial cells (LECs), we reveal a critical link between Nlrp3 and thioredoxin (TRX)-interacting protein (TXNIP), which increases during aging and oxidative stress conditions. We found that aging lenses exhibiting opacity showed elevated ROS levels, increased TXNIP expression, along with upregulation of Nlrp3 inflammasome components, including caspase-1, ASC, IL-1β, IL-18, and gasderminD (GSDMD), with significantly reduced TRX1. mLECs overexpressing TXNIP were more susceptible to hydrogen peroxide (H₂O₂), Lipopolysaccharide (LPS), ultraviolet B (UVB)-induced oxidative stress, displaying increased ROS accumulation, reduced cell viability, and enhanced activation of Nlrp3 inflammasome and its downstream inflammatory mediators, hallmarks of pyroptotic cell death. Conversely, TXNIP knockdown suppressed Nlrp3 inflammasome activation, decreased ROS production, and significantly improved cell survival, indicating a protective effect against oxidative injury. Ex vivo, TAT-HA-Prdx6 delivery inhibited H₂O₂-induced Nlrp3 activation and preserved lens transparency, demonstrating its potent antioxidant and anti-inflammatory effects. Collectively, these findings identify TXNIP as a key regulator of Nlrp3 inflammasome signaling and thereby highlight the therapeutic potential of TXNIP silencing (ShTXNIP) or TAT-HA-Prdx6 delivery to halt Nlrp3-mediated pyroptosis during aging or oxidative stress conditions. Full article

Background/Objectives: The widespread adoption of high-fat diets has contributed to a rising incidence of metabolic disorders and associated cardiovascular diseases. This trend exacerbates myocardial ischemia–reperfusion (I/R) injury following interventional or thrombolytic therapy for acute myocardial infarction, leading to higher mortality and heart failure in affected individuals with metabolic dysregulation, for whom effective interventions are limited. Nuciferine, which possesses anti-inflammatory, antioxidant, and metabolic regulatory properties, has shown potential in improving post-I/R cardiac function, yet its mechanism remains unclear. Methods: This study utilized an ex vivo mouse heart model perfused with high-glucose/high-fatty acid solutions to establish a metabolic stress condition mimicking key aspects of the diabetic milieu and to evaluate the underlying mechanisms of nuciferine. Complementarily, a model of lipotoxicity combined with hypoxia/reoxygenation (H/R) injury was established in human cardiomyocyte cells (AC16). Results: Nuciferine significantly improved post-I/R functional recovery and attenuated succinate accumulation, an effect comparable to the succinate dehydrogenase (SDH) inhibitor dimethyl malonate (DMM). Mechanistically, nuciferine bound to an SDH subunit, inhibiting its activity and subsequent reactive oxygen species (ROS) production via mitochondrial reverse electron transport (RET). It also activated Sirt1-dependent pathways, mitigating apoptosis and mitochondrial dysfunction in AC16 cardiomyocytes. The Sirtuin 1 (Sirt1) inhibitor selisistat (EX527) abolished nuciferine’s protection, while DMM mirrored its efficacy, underscoring nuciferine’s dual role in inhibiting SDH-mediated RET and activating Sirt1 in alleviating I/R injury under metabolic stress conditions. Conclusions: These findings suggest that nuciferine confers cardioprotection by simultaneously attenuating RET-related oxidative stress and activating Sirt1. Full article