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Colon cancer is reported as third most prevalent malignancy worldwide, while sericin being an antioxidant, is now used in biomedical applications due to its biochemical characteristics and has shown potential efficacy to treat colon cancer. Sericin was isolated by the degumming process followed by the characterization by using FTIR, UV, XRD, and SEM techniques to confirm the successful synthesis of SAgNPs and SChiAgNPs. The male Balb C mice were then divided into 13 groups. Group 1: Control, Group 2: DMH (20 mg/kg) (injected (IP) thrice a week for 14 weeks). Groups 3,4,5: Sericin (S) (100 mg/kg), Sericin silver nanoparticles (SAgNPs) (100 mg/kg), and Sericin Chitosan silver nanoparticles (SChiAgNPs) (100 mg/kg) were given orally for 14 weeks respectively. Groups 6,7,8,9 were considered as preventive groups and were given DMH (IP) + 5-FU (IP), DMH(IP) + S (orally), DMH (IP) + SAgNPs (orally), DMH (IP) + SChiAgNPs (orally) respectively for the period of 14 weeks Groups 10,11,12,13 were considered as treatment groups and were given 5-FU (5 mg/kg) (IP), (S) (100 mg/kg) (orally), (SAgNPs) (100 mg/kg) (orally), (SChiAgNPs) (100 mg/kg) (orally) for a period of first 7 weeks after 7 weeks of DMH administration (IP). After 14 weeks period study, blood samples and colon tissue were used for the analysis of biochemical markers i.e., CEA, CA19-9, TIMP-1, and IL-6, IL-8, IL-27, SOD, CAT, GR, GSH, GST, MDA and MMP-7 via ELISA and histopathological analysis. The UV absorption peaks obtained at 435 and 463 nm indicated the formation of SAgNPs and SChiAgNPs formation respectively. FTIR spectra peaks obtained, indicate NH stretching of primary and secondary amine group), (NH stretching of amine salt) (N=C=S stretching of thiocyanate compound), (CC stretching of alkene), (NO stretching of nitro compound), (SO stretching of sulfonyl chloride), (CN stretching of amine) and (C-O-O stretching) for sericin, SAgNPs, and SChiAgNPs, confirming, the presence of theses functional groups. The XRD pattern revealed that SAgNPs and SChiAgNPs had structure crystalline structures. EDX characterization peaks for SAgNPs indicated the presence of silver along with other elements including; calcium, oxygen carbon, while EDX characterization peaks for SChiAgNPs indicated the presence of silver along with other elements including; oxygen, carbon, sodium, phosphorus, Sulphur and chlorine. SEM analysis showed that SAgNPs are of spherical shape, while the SChiAgNPs displayed the rectangular shape. The results for biomarker analysis indicated significantly elevated levels of CEA, CA19-9, TIMP-1, IL-6, IL-8, IL-27, MDA, and MMP-7 in DMH treated group (p ≤ 0.001) which were decreased significantly in SChiAg(T) (p ≤ 0.001). In contrast, levels of SOD, GR, GSH, CAT and GST were reduced significantly in DMH treated group, which were increased significantly in SChiAg(T) (p ≤ 0.001). The histopathological analysis of proximal and distal parts of colon tissue of the DMH-treated group showed low-grade dysplasia (LGD), and high-grade dysplasia (HGD) while SChiAgNPs improved the histopathological changes induced by DMH. The findings suggest that Sericin Chitosan conjugated silver nanoparticles showed their efficacy against DMH-induced colon cancer, making a potential future in the anticancer research field. Show less

Coelonin is a dihydrophenanthrene compound derived from the traditional Chinese medicine Bletilla striata (Thunb.) Reichb.f., which exhibits significant anti-inflammatory activity and effectively inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. Although previous studies have demonstrated the protective effect of Bletilla striata against LPS-induced acute lung injury (ALI), the potential protective role and underlying molecular mechanisms of its major active component, Coelonin, in ALI remain unclear. In this study, an LPS-induced mouse ALI model was established to systematically evaluate the protective effects of Coelonin on ALI. Furthermore, transcriptomic analysis was utilized to investigate the anti-inflammatory mechanisms mediated by Coelonin through the regulation of non-coding RNA (ncRNA)-associated inflammatory pathways. The results indicated that Coelonin significantly ameliorated LPS-induced pathological damage in lung tissues and markedly reduced the levels of inflammatory markers in bronchoalveolar lavage fluid (BALF). In vitro experiments using the murine alveolar macrophages (MH-S) cell line further confirmed the anti-inflammatory activity of Coelonin. Transcriptome analysis revealed that Coelonin markedly upregulates the expression of the ncRNA Gm27505, which was previously found to be downregulated in a mouse model of Alzheimer's disease. To date, there have been no reports on the biological functions of Gm27505. Bioinformatics analysis and real-time quantitative fluorescence PCR (qPCR) confirmed that this ncRNA is primarily localized within the nucleus. Overexpression of Gm27505 in MH-S cells significantly downregulated the expression of inflammation-related genes such as Il6, Tnfα, Il27, and Ccl3 induced by LPS stimulation. Moreover, overexpression of Gm27505 promoted macrophage polarization toward the M2 phenotype while suppressing M1 polarization. These findings suggest that the ncRNA Gm27505 plays an important biological role and is critically involved in the regulation of inflammatory responses. Coelonin may alleviate LPS-induced ALI in mice by up-regulating Gm27505 expression and modulating macrophage polarization. Therefore, Gm27505 may represent a potential target for the prevention and treatment of ALI, providing new research directions for future therapeutic strategies against related diseases. Show less

Gut microbiota-derived compounds are pivotal in modulating host immunity by regulating the functions of various key innate and adaptive immune cells. Epstein-Barr virus-induced gene 3 (EBI3) serves as the beta subunit shared by the heterodimeric cytokines interleukin (IL)-27 and IL-35. Both these cytokines have been documented to inhibit the development of T helper 2 (Th2) and T helper 17 (Th17) cells, while enhancing the function of regulatory T cells (Tregs). EBI3, itself, has also been shown to regulate cell-mediated immune responses. Despite their critical roles in maintaining immune homeostasis, there is a significant lack of robust, high-throughput-compatible assays to evaluate the secretion of IL-27, IL-35, or EBI3. In this study, we detail the development of a novel amplified luminescent proximity homogeneous assay (AlphaLISA™) to quantify EBI3 secretion by tolerogenic dendritic cells. We utilized this assay to screen a library of 9739 small proteins derived from the human gut microbiota to identify compounds that could stimulate EBI3 secretion. Our findings revealed the immunoregulatory potential of VAC18, an unknown protein from Fusicatenibacter saccharivorans (Clostridiumcluster XIVa) which significantly induces the secretion of both EBI3 and IL-27. This is the first study to demonstrate the effect of gut microbiota derived peptides on the balanced secretion of EBI3 and IL-27. Show less

This narrative review aims to critically summarize evidence on the potential contribution of cytokines, including members of the tumor necrosis factor (TNF) superfamily, interleukins (ILs), interferons (IFs), chemokines, lymphokines, and members of the transforming growth factor (TGF) superfamily to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). It also considers the translational relevance of cytokines, including their potential for non-invasive biomarkers or therapeutic targets of MASLD. MASLD and its inflammatory phenotype, metabolic dysfunction-associated steatohepatitis (MASH), are characterized by chronic, low-grade hepatic inflammation, primarily initiated by metabolic contributors and driven by various cytokines. Cytokines are major mediators of the transition from hepatic steatosis to MASH. Some of them seem to be predominantly protective (tumor necrosis factor weak inducer of apoptosis, IL-10, IL-22, IL-25, IL-27), others appear to exhibit a possibly dual-faceted effect, depending on the stage of MASLD (TNF-α, TNF-related apoptosis-inducing ligand, IL-2, IL-6, IL-18, IL-33, IFNs), whereas a third group of cytokines seems to be predominantly harmful, thus driving the progression of hepatic steatosis to MASH, fibrosis, cirrhosis, and possibly to hepatocellular carcinoma. In this regard, some cytokines may prove suitable non-invasive indices for distinguishing MASH or hepatic fibrosis from hepatic steatosis. Additionally, cytokine-based therapies, including anti-TNF-α agents (infliximab, adalimumab, etanercept), NLRP3 inhibitors, recombinant IL-1R antagonist (anakinra), selective C-C chemokine receptor type 2 inhibitors, anti-IL-17 (e.g., secukinumab and ixekizumab) or IL-17R (brodalumab) monoclonal antibodies, and recombinant IL-22, may prove promising pharmacological targets for the management of MASLD. Amounting evidence renders some cytokines key players in the pathophysiology of MASLD, which may possibly have diagnostic and therapeutic implications. Show less

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β-cells. Current therapies fail to address the multiple mechanisms driving disease progression. We developed an oral Female non-obese diabetic (NOD) mice were treated with the oral vaccine, GAST-17, or their combination. Blood glucose levels, islet histology, immune cell infiltration, cytokine profiles, and regulatory T cell populations were assessed. Functional assays included antigen-specific stimulation, adoptive transfer, and analysis of immunoregulatory gene expression. Combination therapy demonstrated superior efficacy in both diabetes reversal and prevention. In reversal studies, diabetes remission was achieved in 80% of mice receiving the combination therapy, compared with 63% in the vaccine-only group and 5% in the GAST-17-only group. In prevention studies, diabetes onset was prevented in 80% of mice receiving the combination therapy, compared with 70% in the vaccine-only group and 30% in the GAST-17-only group. Therapeutic effects were associated with increased antigen-specific regulatory T-cells, reduced islet-infiltrating lymphocytes, preserved insulin-positive islet area and β-cell mass, and modulation of cytokine profiles, including elevated IL-10 and TGF-β and reduced IFN-γ, GM-CSF, IL-1α, and IL-12. Upregulation of immune checkpoint molecules (CTLA-4 and PD-L1) and immunoregulatory mediators (AhR, IDO, and IL-27) was observed, suggesting a potential contribution to immune homeostasis. The combination of the oral Show less

In the non-obese diabetic (NOD) mouse model of autoimmune diabetes, interleukin (IL)-27 stimulates interferon γ (IFNγ) production by CD4 and CD8 T cells and is essential for disease development. Here, we tested the role of IL-27 in cellular communication. Single-cell RNA sequencing and T cell adoptive transfer showed that IL-27 intrinsically controlled the differentiation of islet-infiltrating CD4 T cells by driving them toward an IL-21 Show less

Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe neurological condition associated with high rates of mortality or long-term disability. Despite its clinical significance, the detailed cellular mechanisms underlying HIE remain unclear. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for investigating cellular heterogeneity across development, aging, and disease processes. However, no scRNA-seq studies have yet addressed neonatal HIE. In this study, we employed scRNA-seq to examine cellular heterogeneity during neonatal HIE. We analyzed a total of 87 580 high-quality brain cells to identify transcriptional changes associated with HIE. In the hyperacute phase, we observed astrocytes in response to tumor necrosis factors, involvement of microglia in phagocytosis, Stat3-mediated ischemic responses in oligodendrocyte precursor cells, and an increase in senescent lymphatic endothelial cells. In the acute phase, astrocytes were activated and involved in gliogenesis, while microglia proliferated. Neuroblasts were affected by metal ions, and oligodendrocytes decreased. In the subacute phase, astrocytes involved in inflammation and antigen presentation, while inflammatory microglia highly expressing MHC II were induced by the IL27 and type I interferon pathways and expanded. Additionally, peripheral immune cells played vital roles in HIE. Specifically, neutrophils infiltrated and expanded throughout all phases post-HIE. Spp1 Show less

Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and chronic neuroinflammation. Increasing evidence highlights the interleukin-12 (IL-12) cytokine family-including IL-12, IL-23, IL-27, and IL-35-as central regulators of immune responses in the central nervous system (CNS). IL-12 and IL-23 predominantly promote pro-inflammatory pathways by driving Th1/Th17 activity, microglial activation, and neurotoxicity, whereas IL-27 and IL-35 exert anti-inflammatory and neuroprotective effects through IL-10 induction and expansion of regulatory immune subsets. This review synthesizes disease-specific expression patterns and experimental findings, underscoring the dual pathogenic and protective roles of these cytokines. Therapeutic strategies targeting IL-12 family signaling have shown promise in preclinical and clinical contexts. In AD, blockade of IL-12/IL-23 reduced amyloid burden and improved cognition, while agents such as tadalafil and bergapten enhanced IL-27-mediated neuroprotection via PI3K/Akt, Wnt/β-catenin, and cGMP/PKG pathways. In MS, approaches including p40 blockade (ustekinumab, ABT-874), interferon-β therapy, hematopoietic stem cell transplantation, and B-cell depletion (ocrelizumab) variably suppressed IL-12/IL-23 and augmented IL-27/IL-35, influencing relapse rates and progression. Natural compounds such as curcumin, berberine, and vitamin D further highlight metabolic and dietary opportunities for cytokine modulation. In PD, combinatorial regimens combining herbal formulations with anti-inflammatory agents dampened IL-12-driven macrophage activation and supported dopaminergic neuron survival. Taken together, IL-12 family cytokines emerge as both biomarkers and therapeutic targets in NDs. However, context-dependent activity, blood-brain barrier constraints, and incomplete understanding-particularly of IL-35-pose translational challenges warranting further investigation. Show less

Studies in temporal lobe epilepsy (TLE) have shown that focal inflammation is a key contributor to seizure initiation and maintenance. However, most in vivo studies to date have focused on positron emission tomography (PET) findings. In this exploratory study, we assessed the relationship between multicompartment Neurite Orientation Dispersion and Density Imaging (NODDI) measures (FISO [extracellular/free water], FICVF [neurite density], and ODI [neurite dispersion]) and peripheral immune cells and inflammatory biomarkers. We hypothesized that these biomarkers would be associated with NODDI abnormalities in the affected temporal lobe (aTL). Eighteen patients with TLE and 18 age-matched healthy participants underwent 3 Tesla magnetic resonance imaging (MRI) high angular resolution diffusion imaging. TLE participants also provided peripheral blood samples. We generated NODDI parameter maps (FISO, FICVF, and ODI) and compared the groups using voxelwise two-sample t tests with corrections for multiple comparisons (p < .05), focusing on temporal regions. In TLE patients only, NODDI values extracted from significant clusters correlated with peripheral inflammatory biomarkers. ODI increases in the aTL significantly correlated with pro-inflammatory cytokines such as interleukin (IL)-1α and IL-2. FICVF was lower in the aTL, and this decrease correlated with IL-27 and CD3 Group differences indicate a significant relationship between NODDI biomarkers of injury/neuroinflammation and peripheral immune cells and pro-inflammatory biomarkers in aTL. These novel in vivo findings support further the development of NODDI as a promising non-invasive technique for visualizing neuroinflammation. Further validation of NODDI may enable clinicians to use this approach for monitoring disease progression and treatment response in epilepsy, potentially leading to more personalized treatment strategies. Show less

The COVID-19 pandemic has caused over 7 million deaths, but its legacy extends beyond mortality. SARS-CoV-2 infection induces immune alterations that persist post-recovery, manifesting not only in long COVID (LC) but also in healthy individuals. Cytokines serve as critical orchestrators of these processes. The goal of this study is to investigate post-pandemic immune remodeling through cytokine assessment in both patients with LC and healthy donor, and to compare the post-pandemic population with pre-pandemic controls to find changes in the immune responses and cytokine profiles. A panel of 47 immune mediators (cytokines, chemokines, and growth factors) was measured with the MAGPIX multiplex analysis. LC was characterized by an increase in IL-7, IL-8, IL-17F, IL-18, EGF, FGF-2, PDGF-AA, sCD40L, and MCP-3 and a decrease in IL-4, IL-13, IL-22, IL-27, and FLT-3L. Comparing post-pandemic recovered individuals with pre-pandemic healthy cohort, we saw an upregulation of IL-13 and MCP-3 and a downregulation of MDC, M-CSF, IL-12, and IL-17F. While LC is characterized by persistent immune imbalance-particularly in cytokine networks-our data emphasize the critical need to study healthy donors in both pre- and post-pandemic eras when analyzing and interpreting these changes. Show less

Lung cancer is the second most common malignancy globally and the leading cause of cancer-related deaths. Interleukin-39 (IL-39), a member of the IL-12 family secreted by B cells, acts as a pro-inflammatory cytokine and induces IL-23p19 expression in endothelial cells. Recent findings suggest reduced IL-39 expression in autoimmune thyroid disorders and breast cancer, indicating its possible role in disease progression. To evaluate the role of IL-39 as an early prognostic biomarker in lung cancer. A case-control study was conducted between February and September 2024, involving 180 individuals aged 45-77. The cohort included 90 lung cancer patients (45 with small-cell carcinoma and 45 with non-small cell carcinoma) and 90 healthy controls. Blood samples were analyzed using ELISA to quantify IL-39 and additional tests, including CBC, liver enzymes (ALT, AST, ALP), and lipid profile (cholesterol, triglycerides). Statistical analysis was performed to assess correlations and diagnostic performance. IL-39 levels were significantly lower in stage IV compared to stage III in both cancer types, with a greater reduction observed in small-cell carcinoma. Significant negative correlations were found between IL-39 and total cholesterol, NLR, ALT, AST, and ALP, while positive correlations were noted with hemoglobin and triglycerides. IL-39 demonstrated excellent diagnostic accuracy in small-cell carcinoma with a cut-off value of 3.26950 pg/mL (sensitivity 100%, specificity 100%, AUC 1.000). In non-small cell carcinoma, the cut-off value was 4.88700 pg/mL (sensitivity 63.5%, specificity 92.6%, AUC 0.689). IL-39 shows promise as a predictive and diagnostic biomarker in lung cancer, particularly in small-cell carcinoma, and may play a protective role in disease modulation through immune-related pathways. Show less

As a vital component of the immune system, macrophages play a critical role in the progression of asthma. The two classic polarization states of macrophages, M1 and M2, exhibit distinct functions. M1-polarized macrophages eliminate pathogens through the secretion of pro-inflammatory cytokines, while M2-polarized macrophages secrete anti-inflammatory factors to facilitate tissue repair. However, in asthma, the activation of M1 macrophages is often associated with excessive inflammatory responses, whereas M2 macrophages contribute to airway remodeling and chronic inflammation. These processes collectively exacerbate airway inflammation and remodeling, thereby aggravating asthma symptoms. Reactive oxygen species (ROS), as crucial signaling molecules, have been shown to regulate macrophage polarization and promote both M1 and M2 polarization states. This review summarizes the primary endogenous and exogenous sources of ROS in asthma and elaborates on the mechanisms by which ROS influence M1/M2 polarization of macrophages. Endogenous ROS arise chiefly from NOX2, xanthine oxidase, peroxisomes and mitochondria, whereas ozone and fine particulate matter are major exogenous sources. ROS activate MAPK, NF-κB and NLRP3 cascades, boosting IL-1β, IL-6 and IL-27 release by M1 cells, while low NOX2 flux or mitochondrial H Show less

Altering inflammation can impact the recovering heart's structure and function following myocardial infarction (MI). MAP kinase-activated protein kinase 2 (MK2) regulates the stability of several pro-inflammatory cytokines. Hence, this study was to determine if MK2 deficiency impaired the inflammatory phase of post-MI wound repair. Myocardial infarctions were induced by permanent ligation of the left anterior descending coronary artery in 12-week-old male MK2 Show less

Interleukin-27 (IL-27) is a cytokine that belongs to the IL-6/IL-12 cytokine family with diverse influences on the immune response. Elevated levels of IL-27 cytokine during the neonatal period predispose neonatal mice to more severe infection. Neonatal pups deficient in IL-27 signaling exhibit improved survival and bacterial clearance with reduced systemic inflammation. However, the precise molecular mechanisms that regulate bacterial clearance and the overall immune response in IL-27 receptor a-deficient (KO) mice during neonatal sepsis remain incompletely defined. Analysis of the transcriptome of the neonatal spleen during The results uncovered that during infection WT neonatal mice fail to increase expression of CXCR2 but upregulate the cognate ligand CXCL2 significantly. Conversely, IL-27Rα KO neonates increase CXCR2 expression significantly in the spleen during infection but fail to upregulate CXCL2 transcripts. Splenocytes isolated form septic neonatal KO mice migrated with superior efficiency towards the chemokine CXCL2 compared to WT counterparts. Surprisingly, we also found that splenic monocytes but not the neutrophils account for higher CXCR2 gene expression in the IL-27Rα KO neonatal mice. Monocytes isolated from the spleens of both WT and IL-27Rα KO neonatal pups confirmed that the concentration of CXCL2 regulates CXCR2 receptor expression. We further demonstrated that with regulated CXCL2 chemokine expression levels, IL-27Ra-deficient neonatal mice had more CXCR2+ mononuclear cells present at the site of infection. Overall, our findings suggest that during infection in the absence of IL-27 signaling, a differential expression of CXCR2 and CXCL2 promotes increased migration of mononuclear cells consistent with improved bacterial clearance and tissue homeostasis. This study defines mechanisms that improve the host response in the absence of IL-27 signaling during neonatal sepsis and reinforces the potential for antagonizing IL-27 as a host-directed therapy for neonatal sepsis. Show less

GATA2 establishes transcriptomes governing hematopoietic stem/progenitor cell development. In progenitors, GATA2 represses inflammatory genes (Il6st and Il6ra) encoding IL6ST/GP130 and IL6RA receptor subunits mediating IL-6 signaling. While IL6ST heterodimerizes with IL6RA, IL-11, IL-27, oncostatin M, and leukemia inhibitory factor receptors, IL6RA heterodimerizes exclusively with IL6ST to confer IL-6 signaling. As GATA2-dependent repression is not well understood, we devised a multi-omics strategy to elucidate mechanisms underlying repression and applied the approach to the cytokine/chemokine receptor gene family. Identifying accessible distal and intronic chromatin sites in GATA2-deficient (GATA2 Show less

HBsAg incidence in Egypt is at a range of 2 to 7%. Antiviral immunity is linked to interleukin-27 (IL27), a cytokine that is produced by two genes: EBI3 and p28. IL-27 gene SNPs can alter the susceptibility to infection of HVB by impacting the production and/or function of cytokines. The study aimed to examine the impact of the IL-27 SNPs on the progression of HBV infection among Egyptian individuals. This study included a total 112 patients infected with HBV, and 50 healthy individuals served as controls. The link between the IL-27 SNPs (rs181206 T/C and rs17855750 T/G) and HBV was investigated using real-time PCR. There was no significant correlation between fibrosis stages and the distribution of IL-27 rs181206 T/C and rs17855750 T/G genotypes among HBV patients. Results indicated minimal disparity in the distribution of haplotypes among the study groups. No significant difference in the frequency of the CG, CT, TT, TG, and haplotypes between the groups. This study found no correlation between the presence of IL-27 rs1812006 and IL-27 rs17855750 SNPs and the HBV chronicity. Show less

Acute respiratory distress syndrome (ARDS) is a lung inflammatory condition associated with the accumulation of fluid edema and cell infiltrates into the alveolar space along with dysregulation of the immune response. Current therapeutics are limited to palliative care, i.e., mechanical ventilators, thus highlighting the need to develop targeted therapeutic for ARDS. Interleukin-27 (IL-27) is a multifunctional cytokine with the capability for immune modulation. Our interest lies in exploring the properties of IL-27, particularly as an anti-inflammatory cytokine that functions as an antagonist of IL-6 signaling, as an inducer of anti-viral genes, as a promoter of tissue repair, and as a regulator of both the innate and adaptive immune responses, possessing promising potential as a therapeutic for ARDS. To overcome the challenge of repeated administration due to the short half-life of cytokines, we utilized a cell-based gene therapy approach. An IL-27-expressing plasmid was transfected into adipose mesenchymal stromal cells (ASC) that serve as the gene therapy carriers. For in vitro studies, we treated mono- and co-culture lung lipopolysaccharide (LPS)-induced lung epithelial and monocytes/macrophages cell line with IL-27-expressing ASC (IL-27 ASC) conditioned media (CM) to determine the effects on pro-inflammatory gene expression. For in vivo studies, male C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) and treated either PBS, ASC, or IL-27 ASC (5 × 10 IL-27 ASC CM reduced pro-inflammatory gene expression of lung epithelial and macrophages cultured in both mono- and co-culture systems. Additionally, IL-27 ASC were able to reduce pro-inflammatory markers, decrease cell infiltration into the lungs, promote genes and immune cells involved in tissue repair, and rebalance innate and adaptive immunity in an LPS-induced in vivo model. Collectively, our in vitro and in vivo results show promising potential for IL-27 cell-based gene therapy as a treatment for ARDS. Show less

Intrahepatic immune responses are often insufficient to control hepatitis virus infections. A recent study by Venzin and colleagues demonstrates a detailed mechanism by which an intrahepatic tricellular network and the cytokine IL-27 can augment virus-specific immunity. Show less

Obesity is turning into a more critical problem for public health. Vitamin D The study aims to examine the influence of VD Firstly, a small sample population study was conducted to compare the disparities in serum 25(OH)D A correlation was identified between serum 25(OH)D The study shows that VD Show less

Hyperactivation of cutaneous macrophages promotes the development of chronic pain. Stimulation of nociceptive regions promotes neuroplasticity, which affects pain perception and related physiological responses. However, the specific mechanisms by which cutaneous macrophages sense and elicit nociceptive responses are unknown. Here, we exacerbated the reduction of systemic pain threshold after chronic heart failure (CHF) by silencing follistatin-like 1 (FSTL1), especially the abnormal cutaneous nociceptive sensation at PC6 acupoint, the site associated with cardiac involvement pain. The upregulation of P2Y6 and interleukin-27 expression is intimately linked to the activation of skin macrophages. Hyperactivation of P2Y6 receptor (P2Y6R) may be associated with MHC II M1 Show less

As resident immune surveillance cells within the central nervous system (CNS), microglia exert pivotal biological functions in maintaining CNS homeostasis through dynamic modulation of their proliferative capacity, chemotactic motility, efferocytosis activity, and biphasic secretory mechanisms involving both neuromodulatory factors and pro-inflammatory mediators. These specialized macrophages not only serve as the first line of defense in innate immunity but also orchestrate the regulation of adaptive immune responses; whose functional status directly governs both the physiological integrity of neural circuits and the progression of pathological outcomes. Notably, in neurodegenerative disease models, microglial functional states exhibit pronounced heterogeneity and are tightly regulated by microenvironmental cues. Upon encountering sustained hyperactivation or functional impairment, these cells precipitate a cascade of deleterious events within the neurovascular unit. Building upon these pathophysiological mechanisms, targeted modulation of microglial polarization equilibrium has emerged as a pivotal research focus in developing innovative neuroprotective therapeutic strategies. This review systematically integrates empirical evidence derived from cutting-edge methodologies-including molecular imaging, single-cell multi-omics profiling, and conditional genetic ablation-to mechanistically dissect the dual regulatory roles of microglia in orchestrating neural homeostatic maintenance and driving pathological progression in neurological disorders. Show less

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer's pathophysiology. This study aimed to evaluate the sociodemographic and diagnostic profiles, as well as assess the purinergic signaling, immunological, and redox profiles, of patients after PitNET resection. We collected sociodemographic data and the patients' diagnostic profiles. We also collected blood samples to analyze glycemia, triglycerides, albumin, and ATP levels. The ectonucleotidase activity was determined in peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their redox and immunological profiles. There was a prevalence of gonadotropic macroadenoma derived from PIT-1 cells. We found that patients included in the PitNET group had increased glycemia, serum ATP levels, and ATP hydrolysis in PBMCs. Analyzing their immunological profiles, we found that patients had increased levels of IL-6, IL-10, and TNF, while the IL-27 level was decreased. Regarding their redox profiles, PitNET patients had increased levels of ROS and protein carbonylation. Unexpectedly, patients also showed increased levels of non-protein thiols (NPSHs), total thiols (PSHs), and ascorbic acid. Thus, the dysregulation of purinergic signaling sustained chronic inflammation and oxidative imbalance in PitNET patients for a long time after surgical resection. These data suggest that patients with PitNETs require long-term accompanying to prevent cancer recurrence prognosis. The biomarkers highlighted in this study may be good tools to help the medical approaches. Show less

The quantity and quality of anti-Spike (anti-S) antibodies, rapidly elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are necessary for understanding the immune response induced by infection. Antibody avidity is a good indicator of the quality of antibody response. Interleukin (IL)-21 and IL-27 are two cytokines that play vital roles in the affinity maturation process. Therefore, we decided to investigate whether there are any relationships between the avidities of antibodies against spike and nucleocapsid (N) antigens of SARS-CoV-2 and serum levels of these cytokines in symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) patients. Forty symptomatic COVID-19 patients and 40 asymptomatic carriers were enrolled. Anti-S and anti-N IgG avidity indices (AIs) were determined using a modified enzyme-linked immunosorbent assay (ELISA). Serum levels of IL-21 and IL-27 were quantified by specific ELISA kits. AI values of both anti-S and anti-N IgG were lower in the symptomatic group compared to asymptomatic cases, while only that of anti-N IgG was statistically significant. For IL-21 and IL-27 serum levels, no significant difference between the two groups was shown. Also, we could not find any correlations between cytokine levels and antibody AI values. However, an inverse correlation between anti-S AI value and IL-27 serum level was found in asymptomatic patients. Our study suggests that serum levels of IL-21 and IL-27 cannot predict differences in anti-S and anti-N IgG avidity between symptomatic and asymptomatic COVID-19 patients. Show less

Sepsis, defined as a dysregulated host response to infection, is one of the leading causes of mortality worldwide. It unleashes in the organism a cascade of molecules, cytokines, and proteins which leads to an inflammatory storm. If this response to infection is uncontrolled, any organ is susceptible to damage. Acute kidney injury (AKI) is one of the most frequent organ dysfunctions in septic patients, and while it can be reversible, its presence leads to a higher burden of morbidity and mortality. While serum creatinine is essential in evaluating kidney function, the pathophysiology of AKI is not completely elucidated, and a plethora of novel biomarkers have been studied in the hope of an early diagnosis and fast treatment. While the liver is not as affected by sepsis, it plays an important role as a guardian by providing acute-phase proteins, activating neutrophils, and controlling iron balance. Acute liver failure (ALF) could impair the organism's capacity to contain and eliminate pathogens. Some molecules have been associated with either AKI or ALF, although biomarkers specific for organ dysfunction are difficult to validate. The aim of this review is to understand the role of several molecules in the pathophysiology of sepsis and their clinical ability for diagnosing or predicting sepsis-induced hepato-renal dysfunction. Show less