Search Results (2,483)

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

Hibiscus syriacus L. (HS), native to Eastern and Southern Asia, has been traditionally used in Asian herbal medicine for its anticancer, antimicrobial, and anti-inflammatory properties. Despite these recognized bioactivities, its potential cardioprotective effects, particularly in the setting of heart failure (HF), remain largely unexplored. This study aimed to investigate the effects of HS extracts and its bioactive constituents on angiotensin II (Ang II)-induced cardiac injury using an in vitro model with H9c2 rat cardiomyocytes. Cells exposed to Ang II were pretreated with HS extracts, and assays were performed to assess cell viability, reactive oxygen species (ROS) generation, protein synthesis, and secretion of inflammatory mediators, including tumor necrosis factor-alpha, interleukin 1β (IL-1β), and interleukin 6 (IL-6), as well as chemokine (CCL20) and HF-related biomarkers, such as brain natriuretic peptide (BNP) and endothelin-1. The results demonstrated that HS extracts significantly and dose-dependently attenuated Ang II-induced ROS accumulation and suppressed the secretion of pro-inflammatory cytokines, chemokines, BNP, and endothelin-1. Additionally, HS and its purified components inhibited Ang II-induced protein synthesis, indicating anti-hypertrophic effects. Collectively, these findings highlight the antioxidative, anti-inflammatory, and antihypertrophic properties of HS in the context of Ang II-induced cardiac injury, suggesting that HS may represent a promising adjunctive therapeutic candidate for HF management. Further in vivo studies and mechanistic investigations are warranted to validate its clinical potential. Full article

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article

Crohn’s disease is a chronic inflammation affecting the gastrointestinal tract. To date, patients are commonly treated with corticosteroids or more aggressive biologics for high-risk subjects. Stem Cell Educator therapy has been successfully utilized to treat patients with type 1 diabetes and other autoimmune conditions. A 78-year-old patient with long-standing Crohn’s disease received one treatment with the Stem Cell Educator therapy, followed by clinical, radiographic, pathological examinations and immune marker testing by flow cytometry. After the treatment with Stem Cell Educator therapy, the patient’s clinical symptoms were quickly improved with normal bowel movements, without abdominal pain or rectal bleeding. Flow cytometry analysis revealed a marked decline in inflammatory markers, such as the percentage of monocyte/macrophage-associated cytokine interleukin-1 beta (IL-1β)⁺ cells, which reduced from 94.98% at the baseline to 18.21%, and down-regulation of the percentage of chemokine CXCL16⁺ cells from 91.92% at baseline to 42.58% at 2-month follow-up. Pathologic examination of the biopsy specimens from colonoscopy five weeks and six months post-treatment showed ileal mucosa with no specific abnormality and no significant inflammation or villous atrophy; no granulomas were identified. A follow-up CT scan four and one-half months post-treatment showed no evidence of the previously seen stenosis of the ilio-colonic anastomosis with proximal dilatation. Stem Cell Educator therapy markedly reduced inflammation in the subject with Crohn’s disease, leading to durable clinical, immunological, radiographic, and pathological improvements. Full article

Kynurenic acid (KYNA), a tryptophan metabolite, possesses immunomodulatory properties, although the molecular mechanism of this action has not yet been resolved. In the present study, the effects of KYNA on the secretion of selected cytokines and chemokines by macrophages derived from the human THP-1 cell line are investigated. Furthermore, the involvement of the aryl hydrocarbon receptor (AhR) and the G protein-coupled receptor 35 (GPR35) in mediating the effects of KYNA was examined. In lipopolysaccharide (LPS)-stimulated THP-1-derived macrophages, KYNA significantly reduced IL-6 and CCL-2, but increased IL-10 and M-CSF levels. AhR antagonist CH-223191 reduced the KYNA influence on IL-6, CCL-2, and M-CSF production, while the GPR35 antagonist, ML-145, blocked KYNA-induced IL-10 production. Furthermore, it was shown that THP-1 derived macrophages were capable of synthesizing and releasing KYNA and that its production was increased in the presence of LPS. These findings suggest that THP-1-derived macrophages are a source of KYNA and that KYNA modulates inflammatory responses predominantly through AhR and GPR35 receptors. Our study provides further evidence for the involvement of macrophages in immunomodulatory processes that are dependent on AhR and GPR35 receptors, as well as the potential role of KYNA in these phenomena. Full article

Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants. Full article

Human coronaviruses are a group of viruses that continue to threaten human health. In this study, we investigated the antiviral activity of 4-hydroxychalcone (4HCH), a chalcone derivative, against human coronavirus HCoV-OC43. We found that 4HCH significantly inhibited the cytopathic effect, reduced viral protein and RNA levels in infected cells, and increased the survival rate of HCoV-OC43-infected suckling mice. Mechanistically, 4HCH targets the early stages of viral infection by binding to the epidermal growth factor receptor (EGFR) and inhibiting the EGFR/AKT/ERK1/2 signaling pathway, thereby suppressing viral replication. Additionally, 4HCH significantly reduced the production of pro-inflammatory cytokines and chemokines in both HCoV-OC43-infected RD cells and a suckling mouse model. Our findings demonstrate that 4HCH exhibits potent antiviral activity both in vitro and in vivo, suggesting its potential as a therapeutic agent against human coronaviruses. This study highlights EGFR as a promising host target for antiviral drug development and positions 4HCH as a candidate for further investigation in the treatment of coronavirus infections. Full article

Estrogen-related receptor γ (ERRγ) has been reported to regulate various inflammation-related diseases. Herein, we attempted to evaluate the effects of DN200434 as a modulator for ERRγ in mice with atopic dermatitis (AD). Levels of mRNA and protein expression for ERRγ were evaluated in normal and DNCB-induced AD-diagnosed skin. The effects of DN200434 on the chemokines, inflammatory cytokines, and AKT/MAPK/NFκB pathway signaling were investigated in TNF-α/IFN-γ-treated HaCaT cells. DNCB-induced AD mice received DN200434 intraperitoneally for 10 days. Epidermal thickness at the dorsal aspect of the inflamed skin, spleen index, serum IgE levels, and proinflammatory cytokine levels in the skin lesions were measured. Histopathological evaluations, including assessments of epidermal hyperplasia, dermal inflammation, hyperkeratosis, folliculitis, and mast cell counts, were performed to confirm diagnostic features. Significant elevations in ERRγ expression at the RNA and protein levels were observed in DNCB-induced AD lesions. DN200434 suppressed chemokine and inflammatory cytokine expression and inhibited the elevated phosphorylation levels of AKT, ERK, p38, and NFκB in TNF-α/IFN-γ-treated HaCaT cells. Treatment with DN200434 alleviated DNCB-induced AD symptoms. The histopathological score and levels of infiltrated mast cells were also markedly lower in DN200434-treated AD mice than in vehicle-treated AD mice. Consistently, DN200434 reduced the serum IgE level and mRNA expression of TNFα and IL-6 in AD-diagnosed lesions. Collectively, our findings indicated the feasibility of ERRγ as a therapeutic target for the regulation of AD and that DN200434 can be a useful therapeutic agent in treating AD. Full article

Background and Objectives: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 genotype and augmented inflammatory response in transplant candidates with end-stage alcoholic liver disease (ALD). Materials and Methods: Concentrations of 13 cytokines were measured in 106 end-stage ALD patients without HCC (40 with CC, 40 with CG, and 26 with GG genotype), 35 end-stage ALD patients with HCC, and 19 control patients by cytometric bead array. Results: We found significantly higher concentrations of IL-1, IFN-α, IFN-γ, TNF-α, IL-6, CXCL8, IL-10, IL-12, IL-32, and IL-33 in patients with ALD compared to controls, while the concentration of CCL2 was significantly lower. No differences were observed in the concentration of IL-17 and IL-18. ALD patients with and without HCC had similar cytokine concentrations (p > 0.05 for all comparisons). End-stage ALD patients without HCC of the GG genotype had significantly higher CCL2 concentrations (212.6 [135.9–264.9] pg/mL) compared to end-stage ALD patients without HCC carrying the CC/CG genotypes (141.3 [104.1–201.6] pg/mL, p = 0.002, Mann–Whitney). No significant differences across the genotypes were found for the remaining measured cytokines (p > 0.05). GG carriers also had significantly higher levels of AST and ALT, and lower platelet counts. Conclusions: End-stage ALD patients without HCC who carry the PNPLA3 GG genotype have relatively higher CCL2 levels compared to those with the CC or CG genotypes. Relatively elevated CCL2 concentrations in GG patients might contribute to their increased risk of developing clinical complications compared to CC/CG patients. Full article

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article

Thyroid cancer, the most frequently occurring endocrine neoplasm, comprises a heterogeneous group of histological subtypes, spanning from the indolent papillary thyroid carcinoma (PTC) to the rapidly progressive and lethal anaplastic thyroid carcinoma (ATC). Although conventional therapies, such as surgery and radioactive iodine (RAI), are effective for differentiated thyroid cancers, treatment resistance and poor prognosis remain major challenges in advanced and undifferentiated forms. In current times, growing attention has been directed toward the potential of Natural Killer (NK) cells as a promising immunotherapeutic avenue. These innate immune cells are capable of direct cytotoxicity against tumor cells, but their efficiency is frequently compromised by the immunosuppressive tumor microenvironment (TME), which inhibits NK cell activation, infiltration, and persistence. This review explores the dynamic interaction between NK cells and the TME in thyroid cancer, detailing key mechanisms of immune evasion, including the impact of suppressive cytokines, altered chemokine landscapes, and inhibitory ligand expression. We further discuss latest advancements in NK cell-based immunotherapies, including strategies for ex vivo expansion, genetic modification, and combinatorial approaches with checkpoint inhibitors or cytokines. Additionally, emerging modalities, such as NK cell-derived extracellular vesicles, are addressed. By combining mechanistic insights with advancing therapeutic techniques, this review provides a comprehensive perspective on NK cell-based interventions and their future potential in improving outcomes for patients with thyroid cancer. Full article

Autoimmune CD8⁺ T cell-driven melanocyte destruction constitutes a key pathogenic mechanism in the development of vitiligo. Therefore, the pharmacological inhibition of CD8⁺ T cell effector functions and skin trafficking is a clinically viable therapeutic strategy. This study investigates leflunomide (LEF), an immunomodulatory drug with established safety in autoimmune diseases, for its therapeutic potential in a tyrosine-related protein (TRP) 2-180-induced vitiligo mouse model. Through flow cytometry, immunofluorescence, ELISA, and histopathological analyses, we systematically evaluated LEF’s effects on T cell regulation, chemokine expression, and cytokine profiles. Key findings demonstrated that LEF (20 mg/kg/day) significantly attenuated depigmentation by reducing CD8⁺ T cell infiltration and suppressing the IFN-γ-driven expression of CXCL9/10. Furthermore, LEF restored CD4⁺/CD8⁺ T cell homeostasis and rebalanced pro-inflammatory (IFN-γ, TNF-α, IL-2) and anti-inflammatory (IL-4, IL-10) cytokines, inducing a shift from Th1 to Th2. These results position LEF as an effective immunomodulator that disrupts the IFN-γ-CXCL9/10 axis and re-establishes immune balance, offering a promising repurposing strategy for halting vitiligo progression. Full article

IgG antibodies, signaling via the inhibitory receptor, FcγRIIb, are potent inhibitors of IgE-mediated mast cell activation. We have previously reported that in addition to blocking mast cell degranulation, inhibitory IgG signals shut down a proinflammatory transcriptional program in which mast cells produce cytokines and chemokines known to drive type 2 tissue inflammation. To determine whether such effects of allergen-specific IgG can modulate allergic inflammation in vivo, we examined the airways of mice sensitized to ovalbumin (OVA) by intraperitoneal injection and then challenged with intranasal OVA. Pretreatment with allergen-specific IgG significantly reduced the recruitment of inflammatory cells, including macrophages and eosinophils, into the lungs of OVA-sensitized mice. The bronchoalveolar lavage fluid of OVA-challenged mice contained elevated levels of chemokine ligands (CCL2 and CCL24) and interleukin-5, a response that was markedly blunted in animals receiving allergen-specific IgG. IgG-treated animals exhibited attenuated allergen-induced production of IgE, IL-4, and IL-13, along with impaired OVA-induced goblet cell hyperplasia and Muc5ac expression and suppressed airway hyperresponsiveness, consistent with a shift away from a Th2 response. Using mice with a lineage-specific deletion of FcγRIIb, we demonstrated that each of these protective effects of IgG was dependent upon the expression of this receptor on mast cells. Overall, our findings establish that allergen-specific IgG can reduce allergen-driven airway inflammation and airway hyperresponsiveness and point to a mechanistic basis for the therapeutic benefit of aeroallergen-specific IgG therapy. Full article

In this study, we investigated the expression of TIM-3 and Galectin-9 (Gal-9) in colorectal cancer (CRC) and their associations with oncogenic mutations, MSI status, cytokine profiles, and transcriptional data. TIM-3 and Gal-9 protein levels were significantly increased in CRC tissues compared to matched non-tumor margins (p < 0.05 and p < 0.001, respectively). TIM-3 protein concentration was notably higher in PIK3CA-mutated tumors (p < 0.05), while no associations were found with KRAS, NRAS, BRAF, AKT1, or MSI status. Multiplex cytokine profiling revealed strong correlations between TIM-3 and Gal-9 levels and key immunomodulatory pathways, including IL-10, IL-17, and chemokine signaling. We also observed significant associations with cytokine subsets involved in protumor activity and immune regulation. Gene set enrichment analysis (GSEA) demonstrated that high TIM-3 and Gal-9 expression was associated with upregulation of cell cycle-related pathways, and downregulation of immune signatures, such as interferon responses and TNF-α/NFκB signaling. These findings suggest that increased TIM-3 and Gal-9 expression reflects a shift toward proliferative activity and immune suppression in the CRC tumor microenvironment, highlighting their potential as biomarkers of immunoevasive tumor phenotypes, especially in PIK3CA-mutant CRC tumors. Full article