Search Results (16,963)

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article

Black tea is one of the most widely consumed beverages in the world, second only to water. Its properties are primarily due to the presence of polyphenols, which are associated with various effects, including antioxidant, anticancer, antiviral, and anti-inflammatory activities. These compounds include, among others, theaflavins (TFs) and thearubigins (TRs). The available literature provides numerous reports confirming the positive properties of these compounds. However, it is important to highlight their potential protective effects against oxidative stress induced by heavy metals. This is an important topic, given the ongoing exposure to such pollutants—resulting mainly from industrial development, among other factors. This manuscript provides a summary of the current knowledge on the properties of TFs and TRs and their effect against oxidative stress caused by heavy metals in in vitro studies. The limited amount of research in this area shows that this is still a poorly researched topic. Comparing the results obtained for epigallocatechin gallate (EGCG) from green tea, which has a similar structure to TFs and TRs suggests that they may exhibit similar or even enhanced antioxidant properties. Considering that black tea is consumed much more frequently than green tea worldwide, it is understandable that the antioxidant potential of these two compounds on cells needs to be investigated. Full article

Thesium chinense Turcz. (T. chinense), a perennial herb in the Santalaceae family, exhibits potent antibacterial and anti-inflammatory properties. Transcriptome sequencing was performed on one- and two-year-old T. chinense plants across seedling, flowering, and fruiting stages (all sampled from the same location) using the illumina NovaSeq 6000 platform. A total of 58,706 unigenes were identified, including 1656 transcription factors (TFs). Further analysis classified these TFs into seven functional categories, enabling the reconstruction of a representative TF regulatory network. Differential expression analysis revealed that the number of differentially expressed genes (DEGs) ranged from 2000 to 5000 during different developmental stages in first-year plants, while varying between 1000 and 2000 in second-year plants. Comparative analysis of DEGs between one- and two-year-old plants showed that they were primarily associated with sesquiterpene, triterpene, and terpene skeleton biosynthesis, as well as other metabolic pathways. Additionally, analysis of key genes involved in flavonoid biosynthesis—the major bioactive compounds in T. chinense—revealed their predominant accumulation during the first year of growth. This study provides valuable insights into the developmental biology of T. chinense and establishes a foundation for future research on flavonoid biosynthesis pathway genes and their therapeutic applications. Full article

There is growing interest in the use of natural plant-derived compounds, such as polyphenols (including curcumin), flavonoids, silymarin, anthocyanins, lutein, and zeaxanthin, for the treatment of age-related macular degeneration (AMD). These substances exhibit antioxidant, anti-inflammatory, and protective effects on retinal cells, contributing to the preservation of retinal integrity by modulating the key pathogenic mechanisms of AMD, including oxidative stress, chronic inflammation, and pathological neovascularization. Consequently, they hold potential to support conventional therapeutic approaches and slow disease progression. Current studies highlight their promising role as adjunctive agents in AMD management. This literature review provides a comprehensive analysis of the potential role of the aforementioned natural plant-derived compounds in the prevention and supportive treatment of age-related macular degeneration. It also discusses their natural sources, modes of administration and supplementation, and highlights the importance of a nutrient-rich diet as a key factor in maintaining ocular health. Furthermore, the review synthesizes current scientific knowledge on the ability of natural antioxidants to slow the progression of AMD and outlines future research directions aimed at improving diagnostic methods and developing more effective preventive and therapeutic strategies. Full article

The Tumour Microenvironment (TME) is pivotal for melanoma progression and contributes to therapy resistance. While dermal cell involvement is well established, the role of epidermal cells remains less defined. To explore the contribution of Normal Human Keratinocytes (NHKs) to melanoma biology, we investigated the modification of gene and protein expression of NHKs exposed to melanoma-conditioned medium or maintained in a co-culture system. The analysis focused on pathways related to proliferation, inflammation, Extracellular Matrix (ECM) remodelling, and cell adhesion. Due to the well-documented melanoma–fibroblast crosstalk, Normal Human Fibroblasts (NHFs) and Cancer-Associated Fibroblasts (CAFs) were used as comparative references. Keratinocyte gene expression changes under the influence of melanoma secretome only partially overlapped with those of NHFs and CAFs, indicating cell-type-specific responses. Exposure to melanoma-conditioned medium induced the upregulation of bFGF, CXCL-16, TIMP-2, and E-cadherin in NHKs, alongside downregulating TGF-β and MMP-9. Although bFGF is a recognized pro-tumorigenic factor, the modulation of CXCL-16, TIMP-2, and TGF-β may reflect a protective response. Notably, under co-culture conditions, NHKs exhibited a pronounced pro-inflammatory and ECM-remodelling phenotype, characterized by elevated production of cytokines (IL-1α, IL-1β, and IL-8) and ECM-degrading enzymes (MMP-7, 9, 12, and 13), indicative of a pro-tumoral feature. Collectively, these findings underscore an active role for NHKs in melanoma initiation and progression. Full article

Atherosclerosis is a multifactorial, chronic inflammatory disorder characterized by the progressive accumulation of plaque within the arterial wall. Recent research has highlighted the pivotal role of bioactive peptides in modulating vascular homeostasis and inflammation. Among these, salusin-α and salusin-β have emerged as critical regulators of atherogenesis. These peptides are generated via differential proteolytic processing of preprosalusin: an amino acid precursor encoded by the torsin family 2 member A gene. Despite their common origin, salusin-α and salusin-β exhibit divergent biological activities. Salusin-β promotes vascular inflammation by enhancing oxidative stress, activating the nuclear factor kappa B signaling pathway, and upregulating proinflammatory cytokines as well as adhesion molecules, and it also facilitates foam cell formation by increasing the expression of acyl-CoA/cholesterol acyltransferase 1 and scavenger receptors, thereby contributing to plaque progression. In contrast, salusin-α appears to exert protective, anti-inflammatory, and anti-atherogenic effects by increasing the expression of the interleukin-1 receptor antagonist and inhibiting key proinflammatory mediators. Additionally, these peptides modulate the proliferation of vascular smooth muscle cells and fibroblasts, with salusin-β promoting cellular proliferation and fibrosis via calcium and 3′,5′-cyclic adenosine monophosphate-mediated pathways, while the role of salusin-α in these processes is less well defined. Altered plasma levels of salusins have been correlated with the presence and severity of atherosclerotic lesions, suggesting their potential as diagnostic biomarkers and therapeutic targets. This review provides a comprehensive overview of biosynthesis, tissue distribution, and dual roles of salusins in vascular inflammation and remodeling, emphasizing their significance in the pathogenesis and early detection of atherosclerotic cardiovascular disease. Full article

Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its effectiveness and underlying mechanisms in mitigating renal urate deposition remain inadequately understood. This study investigates the role of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter and the lncRNA H19/miR-21-3p in renal urate deposition, while also validating the therapeutic effects and mechanisms of chicory extract. Renal urate deposition was induced in rats through the administration of potassium oxonate, adenine, yeast extract, and lipopolysaccharide. The levels of serum uric acid (SUA), urate deposition, inflammation, renal function, and histological changes were analyzed. Dual-luciferase assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry were utilized to elucidate the relationship among ABCG2, lncRNA H19, and miR-21-3p. The chemical composition and active ingredients of chicory were analyzed using UPLC-LTQ-Orbitrap-MS, along with molecular docking and cell experiments. In rats with renal urate deposition, serum UA levels were elevated, renal UA excretion was reduced, and levels of low inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hypersensitivity C-reactive protein (hs-CRP), were increased. Additionally, significant renal tissue damage accompanied the urate deposition. Notably, these abnormalities were substantially reversed following treatment with chicory extract. A dual-luciferase reporter assay confirmed the regulatory relationships among miR-21-3p, lncRNA H19, and ABCG2. Immunohistochemical analysis and RT-qPCR demonstrated a significant upregulation of miR-21-3p expression, alongside a downregulation of lncRNA H19, ABCG2 mRNA, and ABCG2 expression in the kidney tissue of rats with renal urate deposition. Chicory extract may exert its inhibitory effect on renal urate deposition by regulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression. Furthermore, UPLC-LTQ-Orbitrap-MS identified 69 components in the chicory extract, including scopoletin, quercetin-3-O-β-D-glucuronide, 11β,13-dihydrolactucopicrin, and kaempferol-3-O-β-D-glucuronide, which were absorbed into the blood of both normal rats and those with renal urate deposition. Molecular docking and cell experiment further validated the effective regulation of 11β,13-dihydrolactucopicrin in ABCG2 and the lncRNA H19/miR-21-3p axis. The downregulation of ABCG2, mediated by the lncRNA H19/miR-21-3p axis, may represent a critical pathogenic mechanism in renal urate deposition. Chicory alleviates this deposition by modulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression, potentially through its component, 11β,13-dihydrolactucopicrin, thereby revealing novel therapeutic insights for renal urate deposition. Full article

Chlorophyll, the green pigment essential for photosynthesis, abundantly found in green vegetables and algae, has attracted growing scientific interest for its potential therapeutic effects, particularly in diabetes management. Recent research highlighted that chlorophyll and its derivatives may beneficially influence glucose metabolism and oxidative stress, key factors in diabetes. This review examines current knowledge on how chlorophyll compounds could aid diabetes control. Chlorophyll and its derivatives appear to support glucose regulation primarily through actions in the gastrointestinal tract. They modulate gut microbiota, improve glucose tolerance, reduce inflammation, and alleviate obesity-related markers. While chlorophyll itself does not directly inhibit digestive enzymes like α-glucosidase, its derivatives such as pheophorbide a, pheophytin a, and pyropheophytin a may slow carbohydrate digestion, acting as α-amylase and α-glucosidase inhibitors, reducing postprandial glucose spikes. Additionally, chlorophyll enhances resistant starch content, further controlling glucose absorption. Beyond digestion, chlorophyll derivatives show promise in inhibiting glycation processes, improving insulin sensitivity through nuclear receptor modulation, and lowering oxidative stress. However, some compounds pose risks due to photosensitizing effects and toxicity, warranting careful consideration. Chlorophyllin, a stable semi-synthetic derivative, also shows potential in improving glucose and lipid metabolism. Notably, pheophorbide a demonstrates insulin-mimetic activity by stimulating glucose uptake via glucose transporters, offering a novel therapeutic avenue. Overall, the antioxidant, anti-inflammatory, and insulin-mimicking properties of chlorophyll derivatives suggest a multifaceted approach to diabetes management. While promising, these findings require further clinical validation to establish effective therapeutic applications. Full article

The protective role of progesterone against estradiol-driven proliferation is essential for preserving endometrial homeostasis. However, the factors that influence the progesterone–estradiol (P4:E2) ratio remain poorly characterized. This study aimed to model this ratio using a machine learning approach to identify key hormonal, anthropometric, demographic, dietary, metabolic, and inflammatory predictors. In addition, it aimed to assess estradiol and progesterone as individual outcomes to clarify whether shared or divergent mechanisms underlie variation in each hormone. NHANES data were used to identify postmenopausal women (n = 1902). An XGBoost model was developed to predict the log-transformed P4:E2 ratio using a 70/30 stratified train–test split. SHAP (SHapley Additive exPlanations) values were computed to interpret feature contributions. The final XGBoost model for the log-transformed P4:E2 ratio achieved an RMSE of 0.746, an MAE of 0.574, and an R² of 0.298 on the test set. SHAP analysis identified FSH (0.213), waist circumference (0.181), and CRP (0.133) as the most influential contributors, followed by total cholesterol (0.085) and LH (0.066). FSH and waist circumference emerged as key predictors of estradiol, while total cholesterol and LH were the most influential for progesterone. By leveraging SHAP-based feature importance to rank predictors of the P4:E2 ratio, this study provides interpretable, data-driven insights into the reproductive hormonal dynamics of postmenopausal women. Full article

This study investigates the effect of walnut green husk extract (WE) on gut microbiota, metabolites, and immune-antioxidant changes in fattening pigs through gut microbiota-metabolite interactions. A total of 60 healthy fattening pigs (Duroc × Landrace × Yorkshire) with an initial body weight of 65.2 ± 3.1 kg were randomly assigned to two groups (n = 30 per group): the control group (NC), which was fed a basal diet, and the WE group, which was fed the basal diet supplemented with 0.1% walnut green husk extract (WE). Dietary supplementation with 0.1% WE significantly increased the relative abundances of beneficial bacteria (e.g., Firmicutes, Lactobacillus) and reduced pathogenic bacteria (e.g., Proteobacteria, Shigella). Untargeted metabolomics identified 170 differentially accumulated metabolites, among which propionic acid—a key short-chain fatty acid with immunomodulatory effects—was significantly upregulated by 1.09-fold (p = 0.03) and showed a positive correlation with beneficial microbial abundances. These metabolites were enriched in glycerophospholipid and α-linolenic acid metabolism pathways, where eicosadienoic acid inhibited the nuclear factor kappa-B (NF-κB) pathway for anti-inflammatory effects, and methyl cinnamate synergistically regulated mitogen-activated protein kinase (MAPK) signaling with Lactobacillus. Serum analyses showed that WE significantly enhanced IgA, IgM, and IgG levels by 3.97-fold, 4.67-fold, and 4.43-fold (p < 0.01), reduced malondialdehyde (MDA) concentration by 82.8% (p < 0.01), and trended to improve antioxidant capacity via glutamine. Mechanistically, WE promoted short-chain fatty acid production by beneficial bacteria, forming a “microbiota–metabolite–immunity” cascade to enhance lipid metabolism and alleviate intestinal inflammation. These findings highlight that WE provides multi-omics evidence for its application as a functional feed additive. Full article

Background: Asymptomatic left ventricular diastolic dysfunction (LVDD) occurs in type 2 diabetes mellitus (T2DM) patients, particularly among the elderly. Aim: This study aimed to identify diastolic function changes over a 52-week follow-up and the predictive factors for LVDD in T2DM patients without atherosclerotic manifestations. Methods: Diastolic function, metabolic profile, atherogenic indexes, and subclinical inflammatory markers were assessed at baseline and after one year in 138 T2DM outpatients. All variables were compared in patients with and without LVDD across three age groups. Results: The patients were 57.86 ± 8.82 years old, 49.3% male, with a mean 5-year diabetes duration and a median HbA_1c of 7.8%. At baseline, 71 patients had grade 1 LVDD, 12 had grade 2 and 3 LVDD, and 15 had indeterminate LVDD. In the elderly group, 29 patients had LVDD. The logistic regression analysis identified age over 65 as an independent risk factor for LVDD (Exp B = 9.85, 95% CI: 1.29–75.36, p = 0.027). LVDD patients had a longer diabetes duration and a higher prevalence of diabetic neuropathy. Elderly patients had the lowest E/A, e’, lateral s’, atherogenic and Castelli risk indexes, and significantly higher E/e’, EDT, LAVI and TNF-alpha values (p < 0.05). After 52 weeks, diastolic function worsened in 27 patients, who had no significant differences compared to those with stable or improved diastolic function. Conclusions: LVDD was common in our T2DM patients without known cardiovascular disease, and age increases the LVDD risk. Echocardiographic assessment is necessary, especially in elderly T2DM patients with co-morbidities, to identify patients at risk of progression to heart failure early. Full article

Background: Previously, we established gemcitabine (Gem)-resistant pancreatic cancer (PaCa) cell lines and showed that the acquisition of Gem resistance is accompanied by enhanced activation of the inflammatory transcription factor nuclear factor-κB (NF-κB). In this study, we focus on CalebinA, a natural compound derived from the rhizomes of turmeric, known for its potent anti-inflammatory properties. It has been suggested that this compound may exert anticancer effects by downregulating the NF-κB signaling cascade. Therefore, we collaborated with Sabinsa Corporation, Japan, to explore its potential application in pancreatic cancer therapy. Methods: We used gemcitabine-resistant pancreatic cell lines to demonstrate the effect of CalebinA on cell toxicity, invasiveness, cytokine levels, NF-κB p65 activity, and tube formation in angiogenesis. Tumor volume and histopathological analysis were used to analyze the effects of CalebinA on tumors induced by the subcutaneous injection of pancreatic cell lines in mice. Results: Treatment with 10 μM CalebinA significantly inhibited NF-κB activity. Gem-resistant PaCa cells exhibited higher invasive and angiogenic capacities than non-resistant parental cells; however, these capacities were markedly suppressed by CalebinA. In vivo, intraperitoneal CalebinA administration every 3 days led to a significant reduction in tumor volume in mice bearing subcutaneous xenografts of the AsPC-1 pancreatic cancer cell line. Immunohistochemical analysis revealed that CalebinA suppressed the expression of Ki-67, CD31-positive microvessel density, and NF-κB p65. Conclusions: These findings suggest that CalebinA holds promise as a novel therapeutic agent for Gem-resistant pancreatic cancer and may be a strong candidate for clinical application. Full article

Background/Objectives: The potential of probiotics and postbiotics as adjunctive or alternative therapies for periodontal disease, which is characterized by chronic inflammation and alveolar bone loss, is gaining increasing attention. In this study, we aimed to elucidate the impact of postbiotic Lactococcus lactis HY449 and Streptococcus thermophilus HY9012 on key cellular processes implicated in the pathogenesis of periodontitis. Methods: THP-1 cells were polarized into M1 macrophages by exposure to Porphyromonas gingivalis lipopolysaccharide in the presence of postbiotics, i.e., heat-killed forms of HY449 or HY9012. The effect of postbiotics on the differentiation of bone marrow-derived macrophages into osteoclasts was analyzed using tartrate-resistant acid phosphatase staining. An in vivo mouse model of ligature-induced periodontitis was used to assess changes in periodontal tissues. Results: The combination of postbiotic L. lactis HY449 and S. thermophilus HY9012 synergistically modulated macrophage polarization by significantly suppressing pro-inflammatory M1 markers and enhancing anti-inflammatory M2 markers. Additionally, postbiotic HY449 and HY9012 inhibited osteoclast differentiation, downregulating the expression of key osteoclastogenic genes and master transcription factors of osteoclast differentiation. In a mouse model of ligature-induced periodontitis, co-treatment with postbiotic HY449 and HY9012 demonstrated synergistic effects in reducing alveolar bone loss. Conclusions: The present findings support the use of postbiotic HY449 or HY9012 as adjunct treatments for the management of periodontitis. Full article

Cadmium (Cd), a pervasive environmental and industrial toxicant, bioaccumulates and exerts severe detrimental effects on skeletal integrity across diverse animal species. Cd-induced bone injury manifests as osteoporosis, osteomalacia, and increased fracture risk, posing significant health and welfare concerns for wildlife and livestock inhabiting contaminated ecosystems. The pathogenesis hinges critically on the disruption of bone remodeling, a tightly regulated process orchestrated by osteoclasts (OCs) responsible for bone resorption and osteoblasts (OBs) responsible for bone formation. This comprehensive review synthesizes the latest mechanistic insights into how Cd disturbs OC and OB function and their intricate crosstalk, leading to net bone loss. Cd directly impairs OB proliferation, differentiation, and mineralization capacity through multiple pathways, including the inhibition of Wnt/β-catenin signaling, induction of oxidative stress and mitochondrial dysfunction, promotion of apoptosis and senescence, and disruption of extracellular matrix protein synthesis. Simultaneously, Cd potently stimulates excessive OC formation and activity. It achieves this by upregulating the RANKL/OPG axis, enhancing reactive oxygen species (ROS) production which activates key OC transcription factors, modulating key signaling pathways, and promoting pro-osteoclastogenic inflammatory cytokine release from bone marrow and immune cells. Critically, Cd disrupts the vital communication between OBs and OCs, perturbing the coupling signals essential for balanced remodeling. Emerging evidence highlights roles for Cd-induced epigenetic modifications and autophagy/mitophagy flux alterations. This narrative review integrates the findings from in vivo animal models and in vitro cellular studies, providing potential therapeutic interventions and mitigation strategies for Cd-induced bone toxicity. Understanding these complex and interacting mechanisms provides a foundation for identifying potential therapeutic targets to mitigate Cd bone toxicity in animals and informs ecological risk assessment and management strategies in contaminated environments. Full article

Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules. Full article