Search Results (2,429)

Chronic HBV infection remains a global health challenge, driving liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver injury is primarily mediated by host immune responses rather than direct viral cytotoxicity. Macrophages, including Kupffer cells, play dual roles in antiviral defense and disease progression. HBV skews macrophages toward an M2-like, immunosuppressive phenotype, promoting viral persistence and fibrogenesis via cytokines such as Interleukin (IL)-10 and Transforming growth factor-beta (TGF-β). Therapeutic strategies targeting macrophage polarization, including Toll-like receptor (TLR) agonists, immune checkpoint inhibitors, and nanoparticle-based systems, are under investigation. Addressing macrophage heterogeneity and the immunosuppressive hepatic microenvironment using advanced models is essential. Modulating macrophages offers a promising avenue to control HBV, restore immune balance, and mitigate liver injury. This review highlights the central role of macrophages in chronic HBV infection and explores emerging therapeutic strategies. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which barrier impairment, immune dysregulation, and gut–skin dysbiosis intersect, prompting growing interest in probiotics as microbiota-modulating adjuncts. We conducted a narrative review of peer-reviewed articles indexed in PubMed, Scopus, and Google Scholar, restricted to publications from 1 January 2018 to 31 October 2025 (searches last run in December 2025). Eligible evidence included randomized controlled trials (RCTs), observational studies, and mechanistic or conceptual reviews addressing microbiome alterations and microbiota-modulating interventions in AD. Most pediatric RCTs using multistrain, Lactobacillus-dominant formulations (often combined with Bifidobacterium) reported modest improvements in AD severity and pruritus and in selected barrier- and inflammation-related biomarkers. However, direct cutaneous microbiome “restoration” outcomes were reported in a minority of studies, and most clinical evidence relies on clinical endpoints and gut–skin axis plausibility rather than longitudinal skin microbiome readouts. Single-strain regimens showed inconsistent effects, and evidence in adolescents and adults remained heterogeneous. Mechanistically, probiotics may enhance short-chain fatty acid (SCFA) signaling, dampen toll-like receptor 2/4 (TLR2/4)-nuclear factor kappa B (NF-κB) activation, and promote interleukin-10 (IL-10)- and transforming growth factor-β (TGF-β)-driven tolerance. Probiotics are a biologically plausible adjunct targeting the gut–skin axis in AD and are generally well tolerated; however, heterogeneity across trials, limited follow-up, inconsistent adverse-event reporting, and scarce skin microbiome endpoints preclude firm clinical recommendations. Full article

This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × Large, body weight = 2.58 ± 0.05 kg) were divided into three treatment groups based on similar body weights and equal numbers of males and females: the blank control group (CON group), the PEDV infection group (PEDV group), and the NG intervention + PEDV infection group (NG + PEDV group) (n = 6 per group). The experiment lasted for 11 days, comprising a pre-feeding period from days 0 to 3 and a formal experimental period from days 4 to 10. On days 4–10 of the experiment, piglets in the NG + PEDV group were orally administered NG (10 mg/kg). On Day 8 of the experiment, piglets in the PEDV and NG + PEDV groups were inoculated with PEDV (3 mL, 10⁶ 50% tissue culture infective dose (TCID₅₀) per milliliter). On day 11 of the experiment, piglets were euthanized for sample collection. PEDV infection caused significant intestinal damage, including a decreased (p < 0.05) villus height in the duodenum and ileum and an increased (p < 0.05) crypt depth in all intestinal segments. This intestinal damage was accompanied by an impaired absorptive function, as indicated by reduced (p < 0.05) serum D-xylose. Further results showed that PEDV compromised the intestinal antioxidant capacity by decreasing (p < 0.05) glutathione peroxidase and catalase activities, and it stimulated the intestinal inflammatory response by upregulating (p < 0.05) the expression of key inflammatory genes, including regenerating family member 3 gamma (REG3G; duodenum, jejunum, colon), S100 calcium binding protein A9 (S100A9; ileum, colon), interleukin 1 beta (IL-1β; ileum, colon), and S100 calcium binding protein A8 (S100A8; colon). PEDV also suppressed the intestinal lipid metabolism pathway by downregulating (p < 0.05) the ileal expression of Solute Carrier Family 27 Member 4 (SLC27A4), Microsomal Triglyceride Transfer Protein (MTTP), Apolipoprotein A4 (APOA4), Apolipoprotein C3 (APOC3), Diacylglycerol O-Acyltransferase 1 (DGAT1), and Cytochrome P450 Family 2 Subfamily J Member 34 (CYP2J34). Moreover, PEDV suppressed the intestinal antiviral ability by downregulating (p < 0.05) interferon (IFN) signaling pathway genes, including MX dynamin like GTPase 1 (MX1) and ISG15 ubiquitin like modifier (ISG15) in the duodenum; weakened intestinal water and ion transport by downregulating (p < 0.05) aquaporin 10 (AQP10) and potassium inwardly rectifying channel subfamily J member 13 (KCNJ13) in the duodenum, aquaporin 7 (AQP7) and transient receptor potential cation channel subfamily V member 6 (TRPV6) in the ileum, and TRPV6 and transient receptor potential cation channel subfamily M member 6 (TRPM6) in the colon; and inhibited intestinal digestive and absorptive function by downregulating (p < 0.05) phosphoenolpyruvate carboxykinase 1 (PCK1) in the duodenum and sucrase-isomaltase (SI) in the ileum. Notably, NG effectively counteracted these detrimental effects. Moreover, NG activated the IFN signaling pathway in the jejunum and suppressed PEDV replication in the colon. In conclusion, NG alleviates PEDV-induced intestinal injury by enhancing the antioxidant capacity, suppressing inflammation, normalizing the expression of metabolic and transport genes, and improving the antiviral ability. Full article

Cytokines are a diverse group of signaling proteins that regulate immune responses by mediating cell communication. Among them, interleukins (ILs) play essential roles in immune regulation, influencing diverse cell processes through tightly controlled signaling networks. Dysregulation of interleukin signaling could lead to chronic inflammation, contributing to the development of autoimmune and inflammatory diseases as well as cancer. IL-26, a cytokine of the IL-10 family, has emerged as a unique modulator of immune function. Although structurally related to IL-10 and sharing one of its receptor subunits, IL-26 exerts distinct biological effects, particularly in promoting inflammatory responses and interacting with extracellular DNA to activate immune pathways. Increasing evidence implicates IL-26 in the development of several chronic conditions, such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, asthma, and various types of cancer. This review summarizes current knowledge on IL-26’s biology, including its structural and receptor characteristics, immunomodulatory functions, and roles in inflammation and disease. Understanding IL-26’s dual functions in normal and inflammatory states may provide insights into novel therapeutic strategies targeting IL-26-mediated pathways in pathological conditions. Full article

Acne vulgaris is a prevalent chronic inflammatory skin disorder affecting over 85% of adolescents. Emerging evidence indicates that Cutibacterium acnes phylotype IA₁ contributes to acne initiation and progression, yet its precise mechanisms in epidermal keratinocytes remain unclear. This study investigated C. acnes IA1’s effects on keratinocyte behavior using an in vitro HaCaT cell model. Cells were co-cultured with live C. acnes IA₁ (CICC 10864) for 24 h. Transcriptomic profiling identified 769 differentially expressed genes (DEGs; adjusted p < 0.05, |log2FC| > 1), including 392 upregulated and 377 downregulated. The protein–protein interaction network analysis via Cytoscape revealed key hub genes (HNRNPA2B1, HNRNPM, RBM39). Enrichment analyses (GO, KEGG, Reactome, DO) highlighted significant involvement of the C-type lectin receptor (CLR) signaling pathway. Validation experiments showed cellular morphological changes, altered structure, and markedly elevated interleukin-6 (IL-6; p < 0.01), underscoring its role in inflammation. These findings suggest C. acnes IA₁ drives acne pathogenesis by regulating hub genes that influence sebaceous gland inflammation, immune activity, and keratinocyte proliferation, positioning them as potential biomarkers for microbiome-targeted therapies. Limitations include the in vitro model’s lack of in vivo skin microenvironment complexity and use of only one representative IA₁ strain. Full article

Bone remodelling is a physiological process influenced by mechanical stimuli such as those generated during orthodontic treatment. Biochemical markers allow the phases of remodelling to be identified, its progression to be assessed, alterations to be detected and scaffold-based tissue regeneration to be evaluated. This study reviews the main markers involved in bone formation and resorption, highlighting their clinical relevance. A literature search was conducted in biomedical databases, selecting studies that analysed crevicular gingival fluid samples in areas of tension and compression. The markers were classified according to their function and location, and their baseline values, temporal variations and methods of analysis were compiled. Among the markers of bone formation, Osteoprotegerin (OPG), Transforming Growth factor β1 (TGF-β1) and Interleukin 27 (IL-27) stand out; while resorption markers include Receptor Activator of Nuclear Factor appa β Ligand (RANKL), Tumour Necrosis Factor (TNF-α) and Interleukin 1β (IL-1β). The results show different expression patterns depending on the type of force applied and the timing of the follow-up, allowing molecular profiles associated with each phase of remodelling to be established. This characterisation improves our understanding of tooth movement and provides a basis for the development of more precise scaffolds and functional biomaterials in orthodontics. Full article

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting—when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its wide application. To address this challenge, several alternative cell-based strategies have been developed. One of these is represented by cytokine-induced killer (CIK) cells, generated from donor peripheral blood mononuclear cells through stimulation with anti-CD3 antibodies, interferon-γ, and interleukin-2. These cells are characterized by a hybrid phenotype, combining T-cell functions with natural killer-like properties, and exhibit antitumor activity in an MHC-unrestricted manner. CIK cells are generally well tolerated and associated with low toxicity but their efficacy is so far modest. Based on the experience of CAR-T in the treatment of B-cell lymphoid disease, CIK cells have been engineered with chimeric antigen receptors (CAR) developing the CARCIK cells. This novel cellular strategy represents a promising approach in the treatment of acute myeloid and lymphoid leukemia relapsed post-allo-HSCT. This review provides an overview of the current CAR-CIK experiences in the setting of acute leukemias and outlines future directions for their clinical translation. Full article

Chronic lymphocytic leukemia (CLL) is a heterogenous disease, with varied clinical outcomes. Multiplex assays used to measure soluble immune checkpoints offer a less laborious method of monitoring patients with CLL, but none of these panels have been validated. The aim of the study was to assess soluble immune checkpoint profiles in patients with CLL and to correlate these with independent prognostic markers such as β2-microglobulin (B2M), Rai stage, fluorescence in situ hybridization (FISH) status, and the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI). We measured plasma levels of soluble interleukin-2 receptor alpha (sCD25), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), galectin-9, programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) using cytometric bead array-based assays. We further measured plasma levels of B2M using an enzyme-linked immunosorbent assay (ELISA) kit. Soluble immune checkpoints were correlated with prognostic markers. The plasma levels of sCD25, TIM-3, galectin-9, PD-1, and PD-L1 were significantly increased in patients with CLL compared to the control group, p < 0.0001. Galectin-9 plasma levels were directly associated with B2M levels (β = 0.65, p = 0.012). Our findings suggest that galectin-9 may provide valuable prognostic significance for patients with CLL. Full article

The extensive use of antibiotics in intensive farming weakens immunity and threatens food safety. Stevia isochlorogenic acid (SICA), a kind of dicaffeoylquinic acid derived from stevia residue, exhibits strong antioxidant activity. This study evaluated the ability of SICA to improve immune function in an immunosuppressed broiler model. SICA significantly increased the spleen, thymus, and bursa of Fabricius indices (p < 0.05), alleviated spleen damage, and elevated serum interleukin-2 (IL-2), IL-4, interferon-γ, IL-1β, tumor necrosis factor-α, immunoglobulins (IgA, IgM, IgG), and complement components C3 and C4 (p < 0.05). Isobaric tags for relative and absolute quantification-based proteomics indicated that SICA enhanced splenic immune function by activating cell adhesion molecules, phagosomes, and the intestinal immune network for IgA production pathways. Quantitative PCR analysis showed upregulation of mRNA and protein levels of B-cell receptor, major histocompatibility complex class II, protein tyrosine phosphatase receptor type C, and neutrophil cytosolic factor 2 (p67phox) and downregulation of C-C motif chemokine receptor 9. Molecular docking demonstrated the strongest binding affinity between SICA and p67phox. Overall, SICA effectively alleviated immunosuppression in broiler chickens and represents a promising natural alternative to antibiotic feed additives. Full article

Airborne particulate matter (PM) is a major environmental pollutant that accelerates skin aging, inflammation, and barrier impairment. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has shown anti-inflammatory and cytoprotective effects, yet its role in protecting full-thickness human skin from pollution-induced damage remains unclear. In this study, human full-thickness ex vivo skin explants were topically exposed to PM (0.54 mg/cm²) and treated with CBD (6.4 mM) administered via the culture medium for 48 h. Proinflammatory mediators (interleukin-6, IL-6; matrix metalloproteinase-1, MMP-1; cyclooxygenase-2, COX-2), oxidative stress markers (reactive oxygen species, ROS; 8-hydroxy-2′-deoxyguanosine, 8-OHdG), the xenobiotic sensor aryl hydrocarbon receptor (AhR), extracellular matrix proteins (procollagen type I C-peptide, PIP; fibrillin), and the barrier protein filaggrin were quantified using ELISA and immunofluorescence. PM exposure triggered significant inflammation, oxidative stress, AhR induction, extracellular matrix degradation, and barrier disruption. CBD selectively counteracted these effects by reducing IL-6, MMP-1, COX-2, ROS, and 8-OHdG levels, downregulating AhR expression, and restoring PIP, fibrillin, and filaggrin expression. No measurable effects were observed in unstressed control tissues. These results demonstrate that CBD protects human skin from PM-induced molecular damage and supports its potential as a functional bioactive ingredient for anti-pollution applications. Full article

Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including baricitinib, ritlecitinib, and durvalumab, restore immune balance and permit anagen reentry. In androgenetic alopecia (AGA), excess dihydrotestosterone and androgen receptor signaling increase DKK1 and prostaglandin D2, suppress Wnt and β-catenin activity, and drive follicular miniaturization. Combination approaches utilizing low-dose oral minoxidil, platelet-rich plasma, exosome formulations, and low-level light therapy enhance vascularization, improve mitochondrial function, and reactivate metabolism, collectively supporting sustained regrowth. Elucidation of intracellular axes such as JAK/STAT, Wnt/BMP, AMPK/mTOR, and mitochondrial redox regulation provides a mechanistic basis for rational, multimodal intervention. Advances in stem cell organoids, biomaterial scaffolds, and exosome-based therapeutics extend treatment from suppression toward structural follicle reconstruction. Recognition of microbiome and mitochondria crosstalk underscores the need to maintain microbial homeostasis and redox stability for durable regeneration. This review synthesizes molecular and preclinical advances in AA and AGA, outlining intersecting signaling networks and regenerative interfaces that define a framework for precision and sustained follicular regeneration. Full article

Natural alkaloids derived from edible and medicinal plants have recently gained attention as bioactive molecules capable of modulating neuroinflammatory processes. Arecoline, the major alkaloid constituent of Areca catechu L. (betel nut), is well known for its cholinergic actions, yet its direct regulatory influence on microglial immune signaling has remained uncertain. In this study, murine BV2 microglial cells were employed to investigate whether arecoline could counteract lipopolysaccharide (LPS)-induced neuroinflammatory responses. Parameters including cell viability, nitric oxide (NO) production, cytokine secretion, and gene expression were assessed, and mechanistic analyses were focused on the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways. Non-toxic doses of arecoline (10–40 μmol/L) markedly decreased NO accumulation and reduced the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Western blot analysis further showed that arecoline suppressed LPS-activated microglial signaling by down-regulating TLR4, inhibiting NF-κB p65 phosphorylation, and limiting PI3K/AKT activation. Collectively, these data reveal that arecoline exerts immunomodulatory and neuroprotective effects through dual signaling regulation in microglia and may serve as a useful pharmacological tool or structural reference for elucidating microglial inflammatory regulation and for guiding the exploration of safer bioactive compounds. Full article

Tirzepatide is a long-acting agonist for the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors approved for the treatment of type 2 diabetes mellitus, weight management in obese patients, or overweight patients with at least one weight-related comorbid condition. The clinical effects of tirzepatide are demonstrated by improved glycemic control, reduced overall appetite, decreased food intake, and body weight. Several studies indicated that the vasculoprotective effects and anti-atherosclerotic potential of tirzepatide extend far beyond glycemic control. Tirzepatide stimulates the mobilization and function of endothelial progenitor cells, which facilitates vascular repair and mitigates hyperglycemia-induced damage. Tirzepatide enhances the activity of endothelial nitric oxide synthase, reduces the activity of endothelial activation molecules such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, promotes vasodilation, and reduces peripheral vascular resistance. Furthermore, the drug inhibits inflammation by suppressing the expression of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6. Moreover, tirzepatide improves lipid profiles by decreasing total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increasing high-density lipoprotein cholesterol. By improving endothelial function, reducing inflammation, and lowering body weight, tirzepatide lowers both systolic and diastolic blood pressure. This article summarizes the data with special emphasis on the mechanisms underlying the anti-atherosclerotic and vasoprotective effects of tirzepatide, based on studies conducted to date. Full article

Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs), toll-like receptor 4 (TLR4) activation, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling. Crucially, many of these phenotypic transitions arise during the earliest stages of neurodegeneration, when glial dysfunction precedes overt neuronal loss and may act as a primary driver of disease onset. This review critically examines glial-centered hypotheses of neurodegeneration, with emphasis on their roles in early disease phases: (i) microglial polarization from an M2 neuroprotective state to an M1 proinflammatory state; (ii) NLRP3 inflammasome assembly via P2X purinergic receptor 7 (P2X7R)-mediated K⁺ efflux; (iii) a self-amplifying astrocyte–microglia–neuron inflammatory feedback loop; (iv) impaired microglial phagocytosis and extracellular-vesicle–mediated propagation of β-amyloid (Aβ) and tau; (v) astrocytic scar formation driven by aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP)/vimentin, connexins, and janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling; (vi) cellular reprogramming of astrocytes and NG2 glia into functional neurons; and (vii) mitochondrial dysfunction in glia, including Dynamin-related protein 1/Mitochondrial fission protein 1 (Drp1/Fis1) fission imbalance and dysregulation of the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Sirt1/PGC-1α) axis. Promising therapeutic strategies target pattern-recognition receptors (TLR4, NLRP3/caspase-1), cytokine modulators (interleukin-4 (IL-4), interleukin-10 (IL-10)), signaling cascades (JAK2–STAT, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase–protein kinase B (PI3K–AKT), adenosine monophosphate-activated protein kinase (AMPK)), microglial receptors (triggering receptor expressed on myeloid cells 2 (TREM2)/spleen tyrosine kinase (SYK)/ DNAX-activating protein 10 (DAP10), siglec-3 (CD33), chemokine C-X3-C motif ligand 1/ CX3C motif chemokine receptor 1 (CX3CL1/CX3CR1), Cluster of Differentiation 200/ Cluster of Differentiation 200 receptor 1 (CD200/CD200R), P2X7R), and mitochondrial biogenesis pathways, with a focus on normalizing glial phenotypes rather than simply suppressing pathology. Interventions that restore neuroglial homeostasis at the earliest stages of disease may hold the greatest potential to delay or prevent progression. Given the complexity of glial phenotypes and molecular isoform diversity, a comprehensive, multitargeted approach is essential for mitigating Alzheimer’s disease and related neurodegenerative disorders. This review not only synthesizes pathogenesis but also highlights therapeutic opportunities, offering what we believe to be the first concise overview of the principal hypotheses implicating glial cells in neurodegeneration. Rather than focusing on isolated mechanisms, our goal is a holistic perspective—integrating diverse glial processes to enable comparison across interconnected pathological conditions. Full article

Objectives: Periodontitis is a multifactorial inflammatory disease initiated by pathogenic bacteria, such as Porphyromonas gingivalis. Resolvin D1 (RvD1) plays a pivotal role in inflammation resolution. This study aimed to identify the mechanism of the regulatory effects of RvD1 on the inflammatory response of human periodontal ligament cells (hPDLCs). Methods: To investigate the mechanism of RvD1’s impact on the hPDLCs, RNA-sequencing (RNA-seq) was used and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to assess the signaling pathways in which NF-κB and MAPK were determined to play a significant role. Alterations in NF-κB and MAPK pathways were verified by immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), and Western blotting (WB). The expression of RvD1 and lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) was assessed by IF and WB. Inflammatory cytokine interleukin (IL) 6 and IL-1β release was measured by ELISA. Results: GO and KEGG analyses indicated that RvD1 regulates the inflammatory process in PDLCs primarily via TLR4-MyD88-mediated NF-κB and MAPK signaling. RvD1 suppressed lipopolysaccharide (LPS)-induced TLR4 and MyD88 expression, inhibited phosphorylation of NF-κB p65 and its inhibitor IKBKB, and attenuated phosphorylation of p38 MAPK, ERK, and JNK. ALX/FPR2 was expressed on hPDLCs and was further upregulated upon treatment with RvD1. RvD1 significantly down-regulated the IL-6 and IL-1β levels in LPS-stimulated hPDLCs. Conclusions: RvD1 regulates the inflammatory response of LPS-stimulated hPDLCs by the TLR4-MyD88-MAPK and TLR4-MyD88-NF-κB signaling pathways, suggesting the potential role of RvD1 in restoring periodontal tissue homeostasis by regulating PDLC response to inflammatory and infectious stimuli. Full article