Search Results (4,338)

Background: Atherosclerosis is a chronic vascular disease triggered by lipid accumulation. Auricularia heimuer is rich in various bioactive compounds that have anti-inflammatory, antioxidant, and hypolipidemic properties. The specific beneficial effects of A. heimuer on atherosclerosis and its underlying mechanisms require further investigation. Methods: In this study, ApoE^−/− mice were utilized as models of atherosclerosis induced by a high-fat diet (HFD) to investigate the effects of A. heimuer. Analyses of gut microbiota and serum metabolomics were conducted to elucidate the potential mechanism. Results: In HFD-fed ApoE^−/− mice, A. heimuer significantly inhibited the increase in body weight, regulated lipid levels, and alleviated aortic lesions. A. heimuer also modulated the abundance of intestinal flora such as Akkermansia and Ruminococcus and altered the levels of serum metabolites, including 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) and N-acetyl galactosamine 4-sulfate. Furthermore, A. heimuer alleviated oxidative stress and inflammatory responses, thereby mitigating atherosclerosis via the Nrf2/NF-κB signaling pathway. Conclusions: These findings suggest that A. heimuer may serve as a potential therapeutic strategy for atherosclerosis. Full article

Pea peptides (PPs), as organic compounds, exhibit a variety of biological functions that make them useful for both the prevention and treatment of metabolic disorders. This study focused on how PPs modified by steam explosion (SE-PP) may help to treat mice with high-fat diet (HFD)-mediated glucose metabolism disorders. The experimental results indicate that both the 100 mg/kg BW SE-PP (SE-PPL group) and 400 mg/kg BW SE-PP (SE-PPH group) experienced substantial decreases in body weight, epididymal and inguinal fat mass, and blood glucose levels of obese mice (notably, the body weight of the SE-PPH group was decreased by 33.13% when compared with that of the HFD group (p < 0.05)). By stimulating the IRS-1/PI3K/AKT signaling system, SE-PP controlled glucose metabolism disorder in adipose tissue, while also inhibiting the TLR4/MYD88/NF-κB pathway to reduce inflammation. Furthermore, SE-PP restored the diversity of the gut microbiota destroyed by HFD. SE-PPH increased the Bacteroidetes/Firmicutes ratio from 0.042 to 0.26 (p < 0.05), which is a key indicator of microbiota balance. In addition, SE-PP enhanced the synthesis of short-chain fatty acids (SCFAs) such as isovalerate, propionate, and acetate, which are essential for maintaining intestinal homeostasis and improving metabolic health (supplementation of SE-PPH increased the levels of total SCFAs by 49.87% in obese mice (p < 0.05)). Full article

Fermented foods are consumed in several cultures worldwide and their health benefits are being increasingly reported. Fermented soybean products in Asia include soybean paste (doenjang), fermented soybeans (cheonggukjang), red pepper paste (gochujang, GCJ), and natto. These fermented foods are reportedly associated with health benefits, including the alleviation of colitis and improvement of immune function. In this study, we investigated the immune-enhancing effects of GCJs produced in four different regions of Korea (including a commercial brand) in cyclophosphamide-treated immunosuppressed rats. The GCJs-treated group showed prevention of weight loss, increased levels of butyric acid in the cecum, and increased weight of lymphoid organs such as the thymus and spleen. Whole blood and serum analysis revealed increased numbers of white blood cells, including granulocytes and lymphocytes, pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α), and elevated immunoglobulin G levels. Additionally, splenocyte proliferation, splenic natural killer cell activity, and immune-related signal pathways (MAPK and NF-κB) were increased. Histological analysis revealed improved tissue structure in the GCJs group. In conclusion, these findings show that GCJs enhance immune function by promoting the growth of immune organs, increasing cytokine production, and activating immune-related signaling pathways. These results suggested the potential of traditional Korean GCJs as a dietary intervention to improve immune health. Full article

Pyruvate is an alpha-keto acid that occurs naturally in living cells. It is a key metabolite in cellular respiration and a substrate for the synthesis of glucose (in gluconeogenesis) and certain amino acids. Exogenous pyruvate, for example in the form of sodium pyruvate or ethyl pyruvate, has potential therapeutic applications due to its antioxidant and anti-inflammatory properties. This review summarises cell culture and animal studies that report the cytoprotective effects of exogenous pyruvate compounds during exposure to environmental pollutants, drugs, UV radiation, and burns. These reports show that the main mechanisms through which exogenous pyruvate exerts its beneficial effects are the neutralisation of reactive oxygen species, protection and stabilisation of mitochondria, maintenance of ATP levels, and inhibition of inflammatory signalling pathways, including the nuclear factor-kappa B (NF-κB) pathway. The article also outlines potential challenges associated with the therapeutic use of exogenous pyruvate. These include the instability of inorganic pyruvate (sodium pyruvate) and the fact that the metabolism of ethyl pyruvate differs between humans and animals. Full article

The gut microbiota plays a critical role in maintaining gastrointestinal homeostasis, immune regulation, and metabolic processes. Recent evidence has highlighted its significant influence on gastric carcinogenesis. Helicobacter pylori, a well-established class I carcinogen, remains the most prominent microbial risk factor for gastric cancer. However, emerging studies indicate that alterations in the broader gastric and intestinal microbial communities, referred to as dysbiosis, may also contribute to tumor initiation, progression, and immune evasion. These microbial shifts can lead to chronic inflammation, genotoxic metabolite production, and modulation of signaling pathways such as NF-κB and Wnt/β-catenin. This review explores the current understanding of the gut microbiome’s contribution to gastric cancer pathogenesis, including microbial signatures associated with precancerous lesions and the tumor microenvironment. Furthermore, the potential of microbiota-based biomarkers and therapeutic interventions, including probiotics, prebiotics, and fecal microbiota transplantation, is discussed as part of emerging precision medicine strategies. Full article

Breast cancer remains a formidable global health challenge, with triple-negative breast cancer (TNBC) posing unique clinical complexities. Characterized by its aggressive nature and limited number of specific therapeutic targets, this breast cancer subtype disproportionately affects African American women, highlighting critical disparities in care. The tumor immune microenvironment (TIME) plays a critical role in breast cancer development and response to immunotherapy, and it is essential in fostering an immunosuppressive and pro-inflammatory niche. Inflammation, primarily mediated by the NF-κB signaling pathway and chemokine signaling, particularly involving CCL2, plays a pivotal role in TNBC progression and therapy resistance. This review describes some of the molecular mechanisms of polyphenols, which are naturally occurring compounds abundant in various dietary sources, and their potential use as therapeutic agents in the management of TNBC. Polyphenolic compounds have been described as modulating the TIME through the inhibition of tumor progression, immune evasion, and therapy resistance, due to their diverse bioactivities, including anti-inflammatory, antioxidant, and anticancer properties, making them attractive candidates for combating the aggressiveness of TNBC and addressing treatment disparities. Polyphenols, such as curcumin, gossypol, butein, epigallocatechin gallate, cardamonin, and resveratrol, have demonstrated efficacy in modulating several signaling pathways within the TIME, which are implicated in the progression of TNBC. This review highlights the potential effects of polyphenols on inflammatory cytokine release, programmed cell death ligand 1 (PD-L1) expression, which is associated with immune evasion by the host cell, and various intracellular signaling cascades, demonstrating their potential use in personalized therapeutic interventions for TNBC. This study also describes differential responses of TNBC cell lines to polyphenol treatment, highlighting the importance of considering genetic variability in therapeutic strategies, as well as the importance of the interaction of polyphenols with the gut microbiome, which may establish the bioavailability and effectiveness of these compounds toward therapeutic outcomes. Further preclinical and clinical studies are warranted to fully elucidate the therapeutic potential of polyphenols and translate these findings into clinical practice, thereby improving outcomes for patients with TNBC worldwide. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

Recent years have provided numerous reports on the mechanisms of action of psychiatric medications (antidepressants, antipsychotics, mood stabilizers, and antidementia drugs) that directly inhibit the growth of cancer cells, as well as on their indirect effects on the psyche and immune system, and their supportive effects on chemotherapeutic agents. The mechanisms of the anticancer activity of psychiatric drugs include inhibition of dopamine and N-methyl-D-aspartate receptors that work via signaling pathways (PI3K/AKT/mTOR/NF-κB, ERK, Wnt/ß-catenin, and bcl2), metabolic pathways (ornithine decarboxylase, intracellular cholesterol transport, lysosomal enzymes, and glycolysis), autophagy, Ca²⁺-dependent signaling cascades, and various other proteins (actin-related protein complex, sirtuin 1, p21, p53, etc.). The anticancer potential of psychiatric drugs seems to be extremely broad, and the most extensive anticancer literature has been reported on antidepressants (fluoxetine, amitriptyline, imipramine, mirtazapine, and St John’s Wort) and antipsychotics (chlorpromazine, pimozide, thioridazine, and trifluoperazine). Among mood stabilizers, lithium and valproates have the largest body of literature. Among antidementia drugs, memantine has documented anticancer effects, while there is limited evidence for galantamine. Of the new psychiatric substances, the antipsychotic drug brexpiprazole and the antidepressant vortioxetine have a very interesting body of literature regarding glioblastoma, based on in vitro and in vivo animal survival studies. Their use in brain tumors and metastases is particularly compelling, as these substances readily cross the blood–brain barrier (BBB). Moreover, the synergistic effect of psychiatric drugs with traditional cancer treatment seems to be extremely important in the fight against chemo- and radio-resistance of tumors. Although there are some studies describing the possible carcinogenic effects of psychiatric drugs in animals, the anticancer effect seems to be extremely significant, especially in combination treatment with radio/chemotherapy. The emerging evidence supporting the anticancer properties of psychiatric drugs presents an exciting frontier in oncology. The anticancer properties of psychiatric drugs may prove particularly useful in the period between chemotherapy and radiotherapy sessions to maintain the tumor-inhibitory effect. While further research is necessary to elucidate the mechanisms, clinical implications, dose-dependence of the effect, and clear guidelines for the use of psychiatric medications in cancer therapy, the potential for these commonly prescribed medications to contribute to cancer treatment enhances their value in the management of patients facing the dual challenges of mental health and cancer. Full article

Chronic inflammation underpins the pathogenesis of both rheumatoid arthritis (RA) and neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review explores the role of C-reactive protein (CRP), particularly its monomeric form (mCRP), as a central molecular link connecting systemic autoimmune inflammation with neuroinflammatory and vascular pathology. In RA, fibroblast-like synoviocytes (FLSs) are activated by CRP through CD32/CD64-mediated signaling, triggering proinflammatory cascades involving NF-κB and p38 MAPK. Recent studies have highlighted that locally synthesized CRP within the synovium may convert to mCRP, amplifying inflammation and tissue damage. Beyond RA, mCRP has been identified within amyloid-beta (Aβ) plaques in AD brains, suggesting a direct role in neurodegenerative pathology. Experimental models also demonstrate that mCRP is upregulated in stroke-affected brain regions and associated with complement activation and blood–brain barrier (BBB) disruption, which is central to AD progression. The convergence of pathways involving IL-6, RAGE (receptor for advanced glycation end-products), and mCRP-mediated complement activation reveals a shared axis of inflammation between RA and AD. This highlights the potential of mCRP not only as a biomarker of chronic inflammation but also as a therapeutic target. Furthermore, evidence from periodontal disease and cardiovascular comorbidities highlights the systemic nature of mCRP-driven inflammation, offering insights into the mechanisms of disease overlap. This review advocates for further mechanistic studies into mCRP signaling, particularly its role at the interface of systemic and neuroinflammation, with the goal of identifying new interventional strategies for patients with RA at elevated risk of neurodegenerative and vascular complications. Full article

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

Despite notable progress in cancer therapy, immune evasion remains a major obstacle to effective treatment outcomes. In the context of spaceflight, astronauts are exposed to unique environmental stressors—particularly microgravity and radiation—that profoundly affect cellular and immune homeostasis. Emerging evidence suggests that microgravity alters key cellular processes, including proliferation, apoptosis, adhesion, and oncogenic signaling pathways such as NF-κB and ERK1/2. Concurrently, microgravity (µg) disrupts immune regulation, potentially facilitating both tumor progression and treatment resistance. Of particular concern is the upregulation of human endogenous retroviruses (HERVs), especially HERV-K and HERV-W, under µg conditions, which may exacerbate inflammatory responses and immune system dysregulation. While some studies indicate that µg may impair tumor growth, others reveal enhanced immune evasion and reduced antitumor immunity. Importantly, insights from µg research extend beyond space medicine and provide translational opportunities for terrestrial oncology, including the development of physiologically relevant 3D tumor models for drug screening, the identification of mechano-sensitive pathways (FAK/RhoA, YAP/TAZ) as therapeutic targets, and novel immunotherapeutic strategies involving epigenetic modulation and checkpoint inhibition. This review critically examines the dual role of µg in modulating cancer progression and immune function. We synthesize findings on how µg shapes immune responses, alters tumor–immune system interactions, and impacts the efficacy of immunotherapeutic approaches. Finally, we highlight translational opportunities and challenges for optimizing cancer immunotherapy and precision oncology in both spaceflight and Earth-based environments. Full article

Objective: Lithospermum erythrorhizon has been extensively used for the clinical treatment of skin diseases, but its material basis and mechanism of action remain unclear. This study integrates network pharmacology, untargeted metabolomics, and in vitro experimental validation to elucidate the anti-inflammatory effects and underlying mechanisms of β-acetoxyisovalerylalkannin, a bioactive naphthoquinone compound isolated from Arnebiae Radix, using inflammatory skin disease models. Methods: Core targets for β-Acetoxyisovalerylalkannin and skin inflammation were identified via network pharmacology and validated through molecular docking. In vitro assays assessed β-Acetoxyisovalerylalkannin’s impact on keratinocyte proliferation, migration, apoptosis, and inflammatory factors (CXCL1, CXCL2, CXCL8, CCL20, IFN-γ, MCP-1, TNF-α, NF-κB). Non-targeted metabolomics identified differential metabolites and pathways. Results: Network pharmacology revealed 66 common targets significantly enriched in the MAPK/STAT3 signaling pathway. In vitro, β-Acetoxyisovalerylalkannin suppressed proliferative viability and hypermigration and induced apoptosis in HaCaTs. Moreover, it downregulated the mRNA levels of inflammatory markers (CXCL1, CXCL2, CXCL8, CCL20, IFN-γ, MCP-1, TNF-α, and NF-κB) by inhibiting the activation of the MAPK/STAT3 signaling pathway. Metabolomics identified 177 modified metabolites, associating them with the arginine/proline, glycine/serine/threonine, glutathione, and nitrogen metabolic pathways. Conclusions: β-Acetoxyisovalerylalkannin exerts protective effects against skin inflammation by reducing abnormal cell proliferation and inflammatory responses, promoting apoptosis, and effectively improving the metabolic abnormalities of HaCaTs. β-Acetoxyisovalerylalkannin is, therefore, a potential therapeutic option for mitigating skin inflammation-related damage. Full article

The emergence of bacterial strains resistant to available antibiotics due to overprescription has prompted a search for alternative treatments. Among the most promising is baicalin, a flavonoid extracted from the roots of Scutellaria baicalensis. Roots, the primary natural source of baicalin, have been extensively explored using emerging extraction technologies such as ultrasonic-assisted extraction and supercritical fluid extraction. These methods offer significant advantages over traditional reflux extraction for baicalin preparation, including shorter extraction times, lower energy consumption, and improved environmental sustainability. Baicalin exhibits remarkable antibacterial activity in vitro and has demonstrated therapeutic efficacy against gastrointestinal infections, meningitis, pulmonary diseases, and sepsis, among other infectious disorders, in animal models. Documented mechanisms of action include disrupting the Escherichia coli membrane, downregulating quorum-sensing gene expression in Pseudomonas aeruginosa, and inhibiting host inflammatory pathways such as PI3K/Akt/NF-κB. However, its clinical translation faces several bottlenecks, including reliance on animal experiment data, low bioavailability, and regulatory compliance issues. This review compares baicalin extraction yields from different natural sources, summarizes the advantages and disadvantages of various extraction technologies, analyzes possible mechanisms of action in treating different bacterial diseases, and discusses outstanding challenges and best strategies for expanded clinical use against bacterial infection. Our aim is to provide a valuable reference for future research and clinical applications. Full article

Chronic, low-grade inflammation is a key contributor to the development of numerous non-communicable diseases (NCDs), including cardiovascular, metabolic, and neurodegenerative disorders. Conventional anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, often present safety concerns with prolonged use, highlighting the need for safer, multi-targeted therapeutic options. Iridoids, a class of monoterpenoid compounds abundant in several medicinal plants, have emerged as promising bioactive agents with diverse pharmacological properties. They exert anti-inflammatory and metabolic regulatory effects by modulating key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR) pathways. This review provides a comprehensive summary of the major iridoid metabolites derived from ten Bulgarian medicinal plant species, along with mechanistic insights from in vitro and in vivo studies. Documented biological activities include anti-inflammatory, antioxidant, immunomodulatory, antifibrotic, organoprotective, antibacterial, antiviral, analgesic, and metabolic effects. By exploring their phytochemical profiles and pharmacodynamics, we underscore the therapeutic potential of iridoid-rich Bulgarian flora in managing inflammation-related and metabolic diseases. These findings support the relevance of iridoids as complementary or alternative agents to conventional therapies and highlight the need for further translational and clinical research. Full article

The internal mammary arteries (IMAs) and coronary arteries share many common characteristics. The inner layer (tunica intima, or intima) of both arteries is lined with a smooth, longitudinally orientated monolayer of endothelial cells (ECs), connective tissue, and an internal elastic lamina that separates the tunica intima from the tunica media (middle layer). The intima of IMAs is lined with an additional protective layer, the neointima, containing vascular smooth muscle cells (VSMCs). The neointima, located between the intima and internal elastic lamina, protects IMAs from damage by assisting in the remodeling of VSMCs. Coarse longitudinal folds in the internal elastic lamina of IMAs partially prevent the infiltration of VSMCs into damaged IMAs, and intimal thickening is thus less likely to occur. Inflamed IMAs resist the migration of monocytes across the endothelial layer and prevent the formation of lipid-rich macrophages (foam cells) within the subintimal or medial layers of arteries. IMAs are thus less likely to form plaques and develop atherosclerosis (AS). Higher levels of prostacyclin (PGI2) in IMAs prevent blood clotting. The anti-thrombotic agents, and production of tumor necrosis factor α (TNF-α), interferon-γ (INF-γ), and visfatin render IMAs more resistant to inflammation. An increase in the production of nitric oxide (NO) by ECs of IMAs may be due to small ubiquitin-like modifier (SUMO) proteins that alter the nuclear factor kappa B (NF-κB) and TLR pathways. The production of reactive oxygen species (ROS) in IMAs is suppressed due to the inhibition of NADPH oxidase (NOX) by a pigment epithelium-derived factor (PEDF), which is a serine protease inhibitor (SERPIN). In this review, a comparison is drawn between the anatomy of IMAs and coronary arteries, with an emphasis on how ECs of IMAs react to immunological changes, rendering them more suited for coronary artery bypass grafts (CABGs). This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article