Search Results (28,102)

Artemether, a derivative of the natural compound artemisinin, is increasingly recognized for its multi-target anti-inflammatory and antioxidant properties. This review systematically elucidates the molecular mechanisms underlying these effects, focusing on artemether’s dual modulation of the MAPK/NF-κB and Nrf2 signaling pathways. We detail how artemether concurrently inhibits the MAPK/NF-κB axis—suppressing IKKβ phosphorylation and IκBα degradation to block NF-κB nuclear translocation—and downregulates p38/contextually modulates ERK phosphorylation. This leads to a significant reduction in key inflammatory mediators, including TNF-α, IL-6, and COX-2. Simultaneously, artemether activates the Nrf2 antioxidant pathway, upregulating HO-1 expression and enhancing the activity of SOD and GSH-Px, which effectively scavenges free radicals and reduces markers of oxidative damage such as MDA and 8-OHdG. The core therapeutic synergy arises from artemether’s disruption of the ROS-NF-κB positive feedback loop, which inhibits neutrophil infiltration and lipid peroxidation, thereby ameliorating tissue injury in experimental models of arthritis and neurodegenerative diseases. Compared to conventional NSAIDs and glucocorticoids, artemether exhibits a favorable safety profile, particularly regarding gastrointestinal effects, and demonstrates unique immunomodulatory potential. Future research directions should prioritize the development of nano-targeted delivery systems and the elucidation of pathway crosstalk at the single-cell level to advance the clinical translation of artemether for chronic inflammatory diseases. Full article

Acne is a prevalent chronic inflammatory skin disorder with a high recurrence rate, in which Propionibacterium acnes (P. acnes) plays a key pathogenic role by colonizing subepidermal pilosebaceous units. The stratum corneum limits drug penetration, rendering conventional topical therapies ineffective. Herein, we report a detachable sustained-release microneedle system named Bacitracin@Hyaluronic Acid–Zein Microneedle (Bac@HA-ZMN) for localized antibacterial delivery in acne therapy. This microneedle patch consists of a dissolvable HA base and zein-based indwelling microneedle tips loaded with bacitracin (Bac) against P. acnes. Mechanical testing showed an average fracture force of 1.6 N per needle tip (n = 100), sufficient for skin insertion. The needle tips enabled Bac delivery to a depth of approximately 500 μm. In vitro transdermal studies demonstrated a cumulative release of 76.1% within 96 h, significantly higher than that of the control group (14.2%). In a murine acne model, the Bac@HA-ZMN treatment group showed a significantly smaller lesion area than the control group, and the immunohistochemical positive expression areas of the inflammatory factors IL-8, MMP-2, and TNF-α were reduced to 0.79%, 4.12%, and 2.14%, respectively, which was caused by the inhibitory effect of Bac on P. acnes. These results demonstrated Bac@HA-ZMN as a promising localized, sustained antibacterial delivery platform for acne treatment. Full article

Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study investigates systemic effects of surgical trauma-activated PRF on MSCs in vitro, analyzing their metabolic activity, inflammatory responses, and regenerative capacity to optimize advanced treatment concepts for severe fractures and injuries. Material & Methods: PRF membranes (T-PRF from trauma patients, C-PRF from healthy controls) were generated. After co-incubation with MSC cells for 24, 72, and 120 h, further investigations of metabolic activity (MTT assay) and gene expression analyses were performed. Results: for MTT assay, results especially showed a significantly higher metabolic activity of T-PRF after 120 h. ELISA-results measuring cytokine levels (CXCL10, IL-6, VEGF, and IDO) exposed a frequent peak in T-PRF group at 72 h, declining slightly at 120 h. In the gene expression analyses, T-PRF exerted a comparatively stronger stimulating effect on MAPK14 and VEGFA after 24 h, while a decrease in gene expression for MAPK8, MAPK14, and RUNX2 was observed over time. Conclusion: surgical trauma-activated PRF seems to be a powerful inducer of early inflammatory and stress responses in MSCs with preserved angiogenic but limited osteogenic signaling. Therefore, a targeted balance between inflammatory activation and sustainable regeneration, as well as optimized preparation and possible combination with immunomodulatory approaches, appear to be crucial for the therapeutic success of PRF-based strategies. Full article

Obesity is a significant risk factor for metabolic diseases and atherosclerotic cardiovascular disease (ASCVD). Exercise exerts beneficial effects partly through myokines secreted by skeletal muscle. This narrative review summarizes current evidence on exercise-induced myokines in obesity. We searched PubMed, Scopus, and Google Scholar up to Jan 2026 using keywords “myokines”, “obesity”, “resistance training”, “aerobic exercise”, and “HIIT”. We focused on six myokines (IL-6, irisin, FGF21, myostatin, apelin, and Metrnl) that are consistently linked to metabolic and cardiovascular health. Key findings are as follows: resistance training effectively increases irisin and decreases myostatin, promoting muscle mass and fat browning; high-intensity interval training (HIIT) induces rapid IL-6 peaks and elevates Metrnl, enhancing anti-inflammatory responses and cardiac function; aerobic exercise improves FGF21 sensitivity and supports long-term metabolic homeostasis. For clinicians and exercise practitioners, a preliminary exercise framework can be suggested based on available human evidence. In obese patients, ≥3 sessions per week of resistance training (60–80% of one-repetition maximum, 8–12 repetitions, 3–4 sets) may be considered to optimize irisin/myostatin balance, combined with ≥150 min per week of moderate-intensity aerobic exercise (50–70% of maximum heart rate) or 75 min per week of HIIT (85–95% of peak heart rate, 4 × 4 min intervals) to improve FGF21 sensitivity and Metrnl levels. These suggestions should be interpreted as hypothesis-generating rather than definitive clinical guidance, given the heterogeneity of included studies and the absence of quantitative synthesis. Nevertheless, they offer a molecular basis for hypothesis-driven precision exercise prescription that requires validation in future prospective studies and randomized controlled trials. Full article

Traditional doubanjiang was investigated to identify endogenous peptides that may contribute to taste maintenance under salt-reduction conditions. Peptidomics identified 1230 peptides at −10logP ≥ 15. UMPred-FRL predicted 161 potential umami peptides, and molecular docking showed that 141 of these peptides could enter the binding site of the T1R1/T1R3 receptor. The successfully docked sequences were mainly short oligopeptides containing three to five amino acid residues. Based on docking scores, six representative candidate peptides were screened, namely EESP, SCPH, SSSGF, PDTE, SYH, and DYDS. Docking and MM-GBSA analyses suggested that these peptides mainly bound within the VFT cavity of T1R1/T1R3, and the interacting residues were dominated by polar residues such as Ser, Asn, Gln, and His and hydrophobic residues such as Tyr, Ile, Leu, and Val. MM-GBSA further suggested that vdW was the major favorable contributor, while Lipo supported complex stability. The umami thresholds of the six peptides ranged from 0.14 to 1.09 mmol/L. Experimental validation by threshold determination and sensory addition showed that all six peptides significantly increased saltiness, whereas their effects on umami differed. PDTE showed the strongest umami-enhancing effect, while SSSGF, SYH, and SCPH exhibited more pronounced saltiness synergy. These results suggest that the screened peptides do not necessarily amplify umami in complex food systems, but may contribute to taste maintenance under salt-reduction conditions through umami support, saltiness synergy, and taste-structure remodeling. Full article

Background/Objectives: Anemia of inflammation (AI) is a prevalent condition linked to systemic inflammation in several chronic diseases, including chronic liver diseases. Hypovitaminosis D is frequently identified in patients with chronic diseases, and its pathogenic role in anemia is currently under investigation. The aim of this study was to prospectively investigate changes in hemoglobin concentration and inflammatory markers in vitamin D-deficient/-insufficient patients with decompensated cirrhosis after initiating vitamin D supplementation, in addition to the supplementation of other micronutrients if needed. Methods: Patients with cirrhosis discharged from decompensation were assessed at baseline and 3 months after vitamin D supplementation. Laboratory parameters of red cell series, nutrition, and micronutrients were assessed in both visits, together with markers of systemic inflammation. Results: Thirty-nine patients were included in the study, of whom 33 completed the 3-month evaluation and were analyzed [age: 62.7 ± 10.7 years; gender: n = 29 (87.9%) males; Charlson index: 5.9 ± 1.6; Model for End-Stage Liver Disease (MELD): 12.4 ± 4.5; baseline hemoglobin (Hb): 11.7 ± 1.8 g/dL (anemia n = 24 (72.7%)); mean 25-hydroxyvitamin D (25OHD) plasma level: 15.5 ± 8.6 µg/L]. A significant increase in plasma 25OHD (40.1 ± 17.8, p < 0.001) and in Hb (12.4 ± 2.0, p = 0.01) was observed at 3 months with a decrease in the prevalence of anemia (n = 17, p = 0.015) and of Interleukin 6 in plasma levels [IL-6, 10.7 (5.8–23.3) vs. 6.5 (4.1–11.8), p = 0.016]. A greater rise in hemoglobin was correlated with higher plasma IL-6 concentration at baseline. Milder anemia and indexes of hypoferremia at baseline, along with optimal renal function and plasma levels of 25OHD at 3 months, were linked to resolution of anemia. Conclusions: Treating vitamin D deficiency together with other micronutrient deficits is associated with inflammation amelioration and improvement in anemia in patients with cirrhosis following discharge from acute decompensation. This paper supports the potential role of vitamin D in the management of anemia in patients with decompensated cirrhosis by modulating systemic inflammation. Full article

Interleukin-17A (IL-17A) is a proinflammatory cytokine that plays a pivotal role in immune responses and tissue homeostasis. Its expression is strictly regulated by transcription factors including RORγt, and it is mainly produced by Th17 cells, γδ T cells, and innate lymphoid cells. IL-17A signals through a heterodimeric receptor complex consisting of IL-17RA and IL-17RC, activating NF-κB, MAPK, and C/EBP pathways via the adaptor protein Act1. IL-17 signaling is counterbalanced by negative regulators including A20 and Regnase-1. Beyond its classical roles in antimicrobial defense and autoimmune inflammation, recent studies have highlighted its functions in the central nervous system, with associations to multiple sclerosis, autism spectrum disorder, and Alzheimer’s disease. The development of IL-17A inhibitors, including the dual IL-17A/F antagonist bimekizumab, has advanced markedly, with demonstrated efficacy in immune-mediated diseases such as psoriasis and psoriatic arthritis. This review provides a comprehensive overview of current knowledge of IL-17A, from its molecular characteristics to clinical applications. Full article

COVID-19 remains a challenge to the global healthcare despite the end of the pandemic, including due to the significant involvement of children in the epidemic process. During the pandemic period, an increase in the incidence of Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) was observed. Currently, their rates remain elevated compared to the prepandemic period. The pathogenetic mechanisms underlying the fulminant course of infection in infants leading to fatal outcomes remain insufficiently understood. In this study, we report for the first time the results of histological and immunohistochemical examination of the lungs in a case of COVID-19-associated SUID in a 2-month-old infant. The absence of similar studies in the available literature limits opportunities for analyzing the pathogenesis of SUID. Our data allow a detailed characterization of the histological changes in the lungs, the localization and range of SARS-CoV-2 nucleocapsid protein expression, the identification of molecular mechanisms underlying apoptosis in the pulmonary microvascular endothelium, and the elucidation of the role of endothelial dysfunction. Particular attention in this article is devoted to the role of cytokines (IL-6, TNF-α, and IFN-γ) in the pathogenesis of hyperacute viral infection. The obtained data demonstrate substantial differences between the observed changes and the classic presentation of COVID-19 in older children. These findings offer prospects for improving prevention strategies and developing targeted therapy for fulminant forms of COVID-19, while also contributing to the understanding of SIDS pathogenesis. Full article

Black mustard (Brassica nigra L.) seeds are a rich source of bioactive phytochemicals; however, their antioxidant, antibacterial, and anti-inflammatory potential has not been comprehensively explored. Therefore, this study aimed to assess antioxidant, antibacterial, and anti-inflammatory effects of black mustard seed extracts obtained from Soxhlet extraction with hexane (HE) and ethanol (EE), and ultrasonic-assisted ethanolic (UE) extraction. HPLC analysis confirmed the presence of sinapic acid in all extracts. Phytochemical profiling revealed that the EE was enriched in phenolic compounds, while the UE exhibited a higher flavonoid content. Accordingly, both EE and UE demonstrated strong antioxidant activities, including radical scavenging capacity, reducing power, and inhibition of lipid peroxidation. All extracts demonstrated antibacterial activity against Staphylococcus epidermidis. The anti-inflammatory potential of extracts was supported by the inhibition of lipoxygenase and protease. The UE showed the strongest lipoxygenase inhibition, while the EE and UE exhibited comparable protease inhibitory effect. Regarding RAW264.7 cells, the extracts were non-cytotoxic and reduced the expression of IL-6 and IL-31. Molecular docking analysis suggested that sinapic acid contributes to the anti-inflammatory activity through interactions with key inflammatory targets. Overall, the EE and UE demonstrated multitarget antioxidant, antibacterial, and anti-inflammatory activities, supporting their potential application in functional and dermatological formulations for inflammation management. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with chronic low-grade inflammation. Interleukin-39 (IL-39), a newly identified cytokine, has been implicated in immune regulation; however, its role in PCOS remains unclear. This study aimed to evaluate serum IL-39 levels in patients with PCOS and its potential as an adjunctive inflammatory biomarker candidate. Methods: This case–control study included 44 patients with PCOS diagnosed according to the Rotterdam criteria and 44 age-matched in the control group. Serum IL-39 levels were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory parameters were recorded. Group comparisons were performed using appropriate parametric and non-parametric tests. Correlation analysis was conducted using Spearman’s coefficient. Multivariable logistic regression analysis was performed to identify independent predictors of PCOS. Receiver operating characteristic (ROC) analysis was used to assess discriminative performance. Results: Serum IL-39 levels were significantly higher in the PCOS group compared to control group (p < 0.001). No significant correlations were observed between IL-39 and other clinical or laboratory parameters. In multivariable analysis, IL-39 was independently associated with PCOS. ROC analysis showed that IL-39 had moderate discriminative ability (AUC = 0.74), with 68% sensitivity and 70% specificity. The combined model including IL-39, body mass index (BMI), luteinizing hormone (LH), and age demonstrated improved performance (AUC = 0.78), with higher sensitivity (86%) and negative predictive value (81%). Conclusions: IL-39 levels are elevated in PCOS and may represent a potential adjunctive inflammatory biomarker candidate. Its diagnostic performance improves when combined with other clinical parameters, supporting a multivariable approach in PCOS evaluation. Full article

Of the many clinical phenotypes of obesity, the most prevalent are metabolically “healthy” (MHO) and metabolically “unhealthy” (MUO) obesities, the latter being associated with a range of comorbidities, including type 2 diabetes mellitus (T2DM). The underlying causes of different obesity phenotypes and the mechanisms of conversion of one phenotype into another have yet to be fully elucidated. However, increasing evidence suggests the key role of low-grade metabolic inflammation (metaflammation) in the pathogenesis of obesity and metabolic dysfunction. The review presents a comprehensive description of changes in immune cell populations and pro-inflammatory mediators, as well as a detailed comparative mapping of the adipose tissue immune landscape during MHO/MUO transition. Based upon a conceptual model for the intensification of metaflammation during MHO progression and conversion to MUO, a pattern of dynamical changes that accompany MHO/MUO transition is described. Though many parameters demonstrate significant differences in multiple cross-sectional and some longitudinal studies, only a few of them (CRP, IL-6, IL-17A, absolute counts of leukocytes and neutrophils) meet the criteria of a validated biomarker in clinical setting. A lack of standardization in MHO definition and heterogeneity in the severity of MUO make the search for predictive biomarkers a challenge. The review also discusses the mechanisms underlying metabolic memory and the incomplete reversibility of metabolic disturbances after bariatric surgery. Full article

Ovarian endometriosis (OE) is a chronic, inflammatory gynecological disorder associated with sterility and an elevated risk of ovarian cancer. Despite its high prevalence, the complex molecular mechanisms governing OE pathogenesis remain poorly investigated. We conducted a comprehensive histopathological and molecular investigation of OE in a cohort of 188 Saudi women (88 patients with OE and 100 healthy controls) using histopathological, qRT-PCR, immunostaining, and Western blot techniques. Histopathological analysis confirmed significant stromal fibrosis and chronic inflammation in endometriotic lesions. Gene expression profiling revealed a pro-proliferative, anti-apoptotic signature, marked by the upregulation of PTTG1 and the downregulation of TNFRSF10D, CDK4, and CDKN1A. Interestingly, we identified a post-transcriptional regulatory paradox in the inflammatory response: while IL-6 mRNA was significantly upregulated, its corresponding protein level was downregulated, suggesting a novel, tightly controlled mechanism to limit excessive local inflammation. Besides the increased autophagic activity and decreased Ubiquitin mRNA levels, epigenetic dysregulation was prominent, characterized by the upregulation of DNA methyltransferase DNMT3B and the downregulation of the histone variant H3.1. These findings elucidate novel molecular pathways underlying OE pathogenesis as evidenced by a post-transcriptional paradox in IL-6 expression, and uncover key dysregulations spanning cell proliferation, apoptosis, inflammation, autophagy, and epigenetic regulation. Full article

Left ventricular assist device (LVAD) implantation is a life-saving therapy for end-stage heart failure but may compromise immune integrity. Mechanical shear stress and surface-induced innate immune activation can trigger bleeding and thromboembolic complications. While thrombotic mechanisms are well characterized, the associated inflammatory response remains poorly studied. We investigated thromboinflammation in patients with terminal heart failure (n = 8) implanted with the HeartWare ventricular assist device. Blood samples were collected before and immediately after implantation, daily for five days, and three months post-implantation. Ten age- and sex-matched healthy individuals served as controls. Samples were analyzed for a broad panel of thromboinflammatory and cell damage biomarkers. Twenty-eight of 43 biomarkers were significantly elevated (p < 0.05) at patient baseline compared with controls, indicating a pre-existing low-grade inflammatory state prior to LVAD implantation. Complement activation products increased markedly immediately after implantation—C3bc, C3bBbP, and the terminal complement complex C5b-9 rose 2.8-, 8.9-, and 6.6-fold, respectively, compared with baseline (p < 0.0001), but returned toward baseline within 24 h. A similar transient increase was observed for TNF, IL-6, IL-8, IL-10, IFN-γ, MMP-8, MMP-9, tissue factor, and prothrombin fragment 1.2 (p < 0.05). LVAD implantation with cardiopulmonary bypass induces a strong but transient immune response, including robust complement activation. Targeting upstream complement pathways may help attenuate downstream thromboinflammatory processes during the acute post-implantation period. Full article

Bergamot essential oil (BEO) has demonstrated antidepressant potential, but its oral application is limited by poor water solubility and undesirable organoleptic properties. In this study, a BEO-loaded beverage was developed based on a whey protein-stabilized oil-in-water emulsion system. The optimal formulation, determined via single-factor experiments combined with orthogonal optimization, consisted of inulin (0.5 g/50 g), milk powder (2.0 g/50 g), sucralose (0.008 g/50 g), and sodium carboxymethyl cellulose (0.04 g/50 g). The resulting beverage remained stable without visible phase separation during 4 months of storage at 4 °C. In a chronic corticosterone treatment (CCT)-induced mouse model of depression, oral administration of the BEO beverage increased activity in the central area of the open field test and exploratory behavior in the elevated plus maze, while reducing repetitive stereotyped behaviors in the marble burying test. At the molecular level, the BEO beverage was associated with reduced levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and corticosteroid (CORT), and increased levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), serotonin (5-HT), dopamine (DA), and norepinephrine (NE). Additionally, the BEO beverage was associated with observed alleviation of neuronal damage in the hippocampal CA3 region, upregulation of brain-derived neurotrophic factor (BDNF), improved gut microbial diversity, and altered host metabolic profiles. Collectively, these findings suggest that the BEO emulsion beverage is a feasible intervention for alleviating depression-like behaviors in the mouse model, and provide initial associative evidence supporting its potential as a functional food for mood management. Full article

Serotonin (5-HT) signaling is strictly controlled by the serotonin transporter (SERT). The present study aims to establish optogenetic approaches for the control of SERT localization and function by modulating the interaction between SERT and its regulatory protein, soluble guanylate cyclase (sGC). We generated several cell lines that stably express blue light-inducible optogenetic elements fused to sGC or the fourth internal loop (IL4) motif of SERT. Our results indicated that blue light-induced SERT-sGC interaction by heterodimerizing SsrA embedded in the membrane-associated improved light-induced dimer (iLID) and SspB-sGCβ1 decreased SERT localization in the plasma membrane, thus reducing the maximum transport velocity of SERT without affecting its K_m for substrate. The light-induced subcellular redistribution of SERT was shown to be attributable to an interference of the SERT-sGC interaction with SERT trafficking but not PKC-mediated internalization. In addition, the light-induced SERT-sGC interaction was blocked by the IL4 peptide or a mutation in the IL4 motif. Furthermore, light-induced exposure of the IL4 motif in iLID decreased the SERT-sGC interaction by displacing SERT from the SERT-sGC complex, thus increasing SERT localization in the membrane and elevating its ability for substrate uptake. This study achieved light-inducible modulation of the protein–protein interaction that allows for the study of biochemical and cellular processes in live cells. Full article