Search Results (2,434)

Acute lung injury may occur after cardiac arrest (CA), with innate immunity likely playing an important role in lung inflammation after CA. This study aimed to survey serial changes in the toll-like receptor (TLR) 4 signaling pathway in post-resuscitation lung injury in CA rats. A randomized animal study was conducted in rats with CA followed by successful cardiopulmonary resuscitation (CPR). The expression of TLR4 pathway biomarkers was analyzed and compared to the sham controls at different time points after CA with CPR. Lung tissues were collected for histological analysis to assess structural damage. Bronchoalveolar lavage fluid (BALF) was analyzed to quantify inflammatory cytokines and to assess changes in regulatory B cells (Bregs) and regulatory T cells (Tregs). Histological examination revealed marked pulmonary hemorrhage and structural injury shortly after CA. CA with CPR increased myeloid differentiation factor 88 (MyD88) mRNA and protein expression compared to controls at 2 h after CA. Cytokine analysis of BALF showed elevated IFN-γ, interleukin (IL)-1α, IL-1β, IL-2, IL-6, and IL-10 at 2 h after CA. A reduction in Bregs was noted at 2 h, whereas Tregs transiently increased between 2 and 4 h but declined at 6 h after CA. The MyD88-dependent signaling pathway appears to be rapidly activated in rats with CA after CPR, which may contribute to the early pulmonary inflammation observed as soon as 2 h after CA. Full article

Obesity has reached epidemic proportions, driven by energy imbalance and limited capacity for adaptive thermogenesis. Brown (BAT) and beige adipose tissues dissipate energy through non-shivering thermogenesis (NST), primarily via uncoupling protein-1 (UCP1), making them attractive targets for increasing energy expenditure (EE). The canonical β-adrenergic pathway robustly activates NST in rodents through β3 adrenoceptors; however, translational success in humans has been limited by low β3 expression, off-target cardiovascular effects, and the emerging dominance of β2-mediated signaling in human BAT. Consequently, attention has shifted to non-adrenergic and UCP1-independent mechanisms that offer greater tissue distribution and improved safety profiles. This review examines a broad spectrum of alternative receptors and pathways—including GPRs, TRP channels, TGR5, GLP-1R, thyroid hormone receptors, estrogen receptors, growth hormone, BMPs, sirtuins, PPARs, and interleukin signaling—as well as futile substrate cycles (Ca²⁺, creatine, and glycerol-3-phosphate) that sustain thermogenesis in beige adipocytes and skeletal muscle. Pharmacological agents (natural compounds, peptides, and small molecules) and non-pharmacological interventions (cold exposure, exercise, diet, and time shift) targeting these pathways are critically evaluated. We highlight the translational gaps between rodent and human studies, the promise of multimodal therapies combining low-dose adrenergic agents with non-adrenergic activators, and emerging strategies such as sarco/endoplasmic reticulum calcium ATPase protein (SERCA) modulators and tissue-specific delivery. Ultimately, integrating adrenergic and non-adrenergic approaches holds the greatest potential for safe, effective, and sustainable obesity management. Full article

Adipose-derived mesenchymal stem cells (AD-MSCs) secrete various growth factors that activate skin cells. This study investigated the effects of crude extracts and isolated compounds, hitorin A and hitorin B, from Chloranthus quadrifolius on AD-MSCs. The crude extract and hitorins A and B obtained from C. quadrifolius promoted cell proliferation. Furthermore, they suppressed the accumulation of excessive lipid droplets and reduced the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein alpha, and adiponectin. The extract and hitorins A and B increased the expression of stemness marker genes, including SRY-box transcription factor 2, homeobox protein NANOG, and octamer-binding transcription factor 4. For anti-aging effects, the crude extract and hitorins A and B significantly inhibited senescence-associated-β-galactosidase activity and the gene expression of p16, p21, and p53 under hydrogen peroxide-induced oxidative stress. Additionally, they suppressed the production of intracellular reactive oxygen species and the gene expression of interleukin-6 and interleukin-8. These findings indicate that crude extracts and hitorins A and B derived from C. quadrifolius suppress excessive adipogenic differentiation, promote cell proliferation while enhancing stem cell characteristics, and reduce oxidative stress-induced cellular aging through antioxidant and anti-inflammatory activities. These results suggest that they are effective cosmetic ingredients for skin rejuvenation and anti-aging. Full article

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have transformed the treatment landscape for estrogen receptor-positive (ER+) breast cancer, yet resistance remains a major clinical challenge. Although CDK4/6i induce G₁ arrest and therapy-induced senescence (TIS), the exact nature of this senescent state and its contribution to resistance are not well understood. To explore this, we developed palbociclib- (2PR, 9PR, TPR) and abemaciclib- (2AR, 9AR, TAR) resistant ER+ breast cancer sublines through prolonged drug exposure over six months. Resistant cells demonstrated distinct phenotypic alterations, including cellular senescence, reduced mitochondrial membrane potential, and impaired glycolytic activity. Cytokine profiling and enzyme-linked immunosorbent assay (ELISA) validation revealed a non-canonical senescence-associated secretory phenotype (SASP) characterized by elevated growth/differentiation factor 15 (GDF-15) and serpin E1 (plasminogen activator inhibitor-1, PAI-1) and absence of classical pro-inflammatory interleukins, including IL-1α and IL-6. IL-8 levels were significantly elevated, but no association with epithelial–mesenchymal transition (EMT) was observed. Resistant cells preserved their epithelial morphology, showed no upregulation of EMT markers, and lacked aldehyde dehydrogenase 1-positive (ALDH1+) stem-like populations. Additionally, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) was strongly upregulated in palbociclib-resistant cells. Together, these findings identify a distinct, non-canonical senescence phenotype associated with CDK4/6i resistance and may provide a foundation for identifying new vulnerabilities in resistant ER+ breast cancers through targeting SASP-related signaling. Full article

Matrix metallopeptidases (MMPs) are enzymes that, in balance with their inhibitors, play a vital role in extracellular matrix remodelling, particularly during orthodontic tooth movement (OTM). Despite growing interest, significant research is still required to fully comprehend the mechanisms and signalling pathways involved in periodontal ligament remodelling and OTM, particularly those mediated by MMPs. This review explores recent in vitro and in vivo evidence on how specific MMPs—namely, MMP-1, -2, -3, -8, -9, -12, -13, and -14—respond to compressive and tensile forces, regulate collagen degradation, and influence periodontal ligament fibroblast and osteoblast behaviour, ultimately shaping tissue resorption and formation. We also summarize the roles of periodontal ligament cells, hypoxia, the neurovascular and immune systems, and well-known molecules—including receptor activator of nuclear factor kappa β, receptor activator of nuclear factor kappa β ligand, osteoprotegerin, macrophage colony-stimulating factor, tumour necrosis factor α, transforming growth factor, and interleukins—in orchestrating these responses. Finally, we address the clinical relevance of these pathways, highlighting the potential for therapeutic strategies targeting MMPs activity. Overall, this review underscores the pivotal contribution of MMPs to extracellular matrix turnover and tissue adaptation during OTM and suggests that modulating the MMPs/tissue inhibitors of matrix metallopeptidase (TIMPs) balance may enhance orthodontic outcomes. Full article

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