Blood Cytokine Levels Research Articles

Interleukin-6 and Lymphocyte-to-Monocyte Ratio Indices Identify Patients with Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a fatal biliary tract cancer with a dismal prognosis due to ineffective diagnostic tools with limited clinical utility. This study investigated peripheral blood indices and cytokine levels to diagnose iCCA. Blood samples were collected from healthy subjects (n = 48) and patients with advanced-stage iCCA (n = 47) during a phase I and then phase II trial, respectively. Serum cytokines were measured using a flow cytometer. The peripheral blood indices were estimated based on laboratory data. Multi-linear regression analysis was applied, followed by a probability transformation. The cut-off value and model accuracy were determined using the receiver operating curve (ROC) and the area under the curve (AUC). The interleukin-6 (IL6) and lymphocyte-to-monocyte ratio (LMR) were potential predictors of iCCA [AUC = 0.91 (0.85-0.97) and 0.81 (0.68-0.93); sensitivity = 0.70 and 0.91; specificity = 0.91 and 0.85, respectively]. Patients with IL6 concentrations higher than 11.635 pg/mL (OR = 23.33, p < 0.001) or LMR lower than 7.2 (OR = 58.08, p < 0.001) are at risk of iCCA development. Patients with IL6 levels higher than 21.83 pg/mL, between 15.95 and 21.83 pg/mL, between 8.8 and 15.94 pg/mL, and lower than 8.8 pg/mL were classified as very high-, high-, intermediate-, and low-risk, respectively. Patients with an LMR between 1 and 3.37, 3.38 and 5.76, 5.77 and 7.18, and higher than 7.18 were classified as very high-, high-, intermediate-, and low-risk, respectively. LMR is recommended for iCCA screening since the estimation is based on a routine laboratory test, which is available in most hospitals.

A multivariate meta-analysis of peripheral cytokine levels in obsessive compulsive disorder

IntroductionObsessive-compulsive disorder (OCD) is a common psychiatric disorder. It is considered that dysregulation of cytokine levels is related to the pathophysiological mechanism of OCD. However, the results of previous studies on cytokine levels in OCD are inconsistent.ObjectivesTo perform a meta-analysis assessing cytokine levels in peripheral blood of OCD patients.MethodsWe searched in PubMed, Web of Science, and Embase from inception to March 31, 2023 for eligible studies. We conducted multivariate meta-analysis in combined proinflammatory cytokines (interleukin-6 [IL-6], IL-1β, IL-2, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]) and combined anti-inflammatory cytokines (IL-10 and IL-4) respectively, and calculated the same meta-analysis in each cytokine. We also performed sensitivity analysis and publication bias tests, as well as subgroup analysis (i.e. different age groups, varied cytokine measurement methods, medication treated or naïve, and presence of psychiatric comorbidities) and meta-regression analysis (variables including patients’ sex ratio, age, age at symptom onset, illness duration, scores of Y-BOCS, family history of psychiatric disorders, and BMI).Results17 original studies (13, 13, 10, 5, 4, 3, 2 studies for IL-6, TNF-α, IL-1β, IL-10, IL-2, IL-4, and IFN-γ, respectively), 573 patients (mean age, 25.2; 50.3% female) and 498 healthy controls (HC; mean age, 25.3; 51.4% female) were included. The results showed that the levels of combined pro- or anti-inflammatory cytokines and each signle cytokine were not significantly different between OCD patients and HC (all P&gt;0.05), with significant heterogeneities in all analyses (I2 from 79.1% to 91.7%). We did not find between-group differences in cytokine levels in all subgroup analyses. Meta-regression analysis suggested that age at onset (P=0.0003) and family history (P=0.0062) might be the source of heterogeneity in TNF-α level. Sensitivity analysis confirmed that all results were stable, except for IL-4 where different cytokine measurement methods may be the contributing factor. Egger test did not find publication bias.ConclusionsOur study showed no difference in cytokine levels between OCD patients and HC, but age at onset and family history may affect TNF-α level. Confounding factors such as age at onset, family history, and cytokine measurement methods should be controlled in future studies to further explore the immune mechanism of OCD.Disclosure of InterestNone Declared

Abstract 3860: Characterizing peripheral immune correlates of tumor response in breast cancer patients immunized with the P10s-PADRE vaccine

Abstract Introduction: We demonstrated that vaccination of HR+/HER2− breast cancer subjects with P10s-PADRE cancer vaccine in combination with standard-of-care chemotherapy led to generation of antibodies (Ab), activation of Natural Killer (NK) and T cells, increases in IFNγ and TNFα, and increases in TILs and stromal CD3+ T cells. The current study was conducted to assess the vaccine's efficacy, particularly focusing on tumor shrinkage and pathologic Complete Response (pCR). Additionally, it aims to explore the association of specific peripheral-blood immune responses, such as antibody levels and NK and T-cell activation, with pCR and objective reduction in primary tumor size. Methods: Blood samples collected at baseline and after treatment of at least 25 subjects were used in characterization of immune responses. Serum and plasma samples were used in ELISA, cytokine, and glycan-array assays to measure anti-peptide and anti-glycan antibodies and blood-cytokine levels. Peripheral blood mononuclear cells (PBMCs) were interrogated by RNA-seq, flow cytometry, and ELISpot assays. Results: We observed that high levels of anti-peptide and anti-GD2 antibody responses correlated with pCR. Ab response was positively correlated with differential expression of CD56, GZMA, IFNγ, NKp46, and CD8b, among which GZMA and NKp46 showed a statistically significant association. Vaccine-induced functional cellular immune responses (measured by differential expression of IFNγ, GZMA, CD8, CD69, NKp46, CD56, and PRF1) correlated with reduction of primary tumor size. We also observed substantial differences among immune responders vs non-responders in immune gene expression and in cytokine production in post-immune PBMCs after specific and polyclonal stimulation. Conclusions: The data suggest that immunization of HR+/HER2− breast cancer patients with P10s-PADRE in combination with chemotherapy leads to both humoral and cellular immune responses. While induction of a robust antibody response is a good marker for potential clinical efficacy, vaccine-associated increases of the ratio of CD8+ cells and the expression of CD69, CD8b, GZMA, IFNγ, NKp46, and PRF1 seem to serve as additional efficacy indicators. Future studies are underway to validate these findings and establish reliable prognostic biomarkers. Citation Format: Fariba Jousheghany, John P. Lee, Bernice Nounamo, Vinay Raj, Jennifer L. Faulkner, Eric Siegel, Issam Makhoul, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Characterizing peripheral immune correlates of tumor response in breast cancer patients immunized with the P10s-PADRE vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3860.

Down-regulation of A20 mRNA expression in peripheral blood mononuclear cells from MDS patients

ABSTRACT Myelodysplastic syndrome (MDS) is characterized by activated inflammatory signaling and affects prognosis. Targeting inflammatory signaling may provide a way to treat the disease. We were curious whether there were changes in A20 in peripheral blood mononuclear cells (PBMC) of MDS patients. Therefore, we conducted a study with 60 clinical samples, including 30 MDS patients and 30 healthy controls. All patients with MDS were diagnosed and classified according to the criteria of the 2016 World Health Organization. The study was performed in accordance with the guidelines of the Declaration of Helsinki. Using Quantitative Real-Time RT–PCR, we discovered that A20 mRNA expression in PBMC of the MDS group was significantly lower than that in the control group (P < 0.001). Additionally, using Luminex Liquid Suspension Chip, we observed elevated plasma levels of pro-inflammatory IL-8 and TNF-α in the MDS group compared to the healthy control group (P < 0.001). We did not find a significant correlation between A20 mRNA and clinical characteristics (age, sex, concentration of hemoglobin, neutrophils count, platelets count, percent of blasts, and WHO classification) of the patients, nor between A20 mRNA and plasma cytokines (data not shown). Our study found down-regulated of A20 and increased levels of pro-inflammatory cytokines in the peripheral blood of MDS patients, providing further evidence for the activation of inflammatory signals in MDS.

Inflammatory Modulation of Interleukin-17 and -23 in Long COVID Diabetic Patients

Background: The global COVID-19 pandemic has brought forth a persistent challenge in the form of Post-COVID-19 Syndrome (PCS) or Long COVID, affecting approximately 1 in 10 cases. Among the various risk factors, diabetes has emerged as a significant predictor of severe outcomes, with hyperglycemia and hyperinflammation playing pivotal roles. Despite the known association, the exact mechanisms linking diabetes to Long COVID remain elusive, prompting the need for further investigation. This study aimed to explore the relationship between immune responses, particularly interleukin-17 and -23 levels, and Long COVID severity in diabetic individuals. Method: Fifty diabetic patients with Long COVID were compared with fifty diabetic controls. Blood cytokine levels were measured, and Long COVID severity was assessed using the Long COVID Severity Scale (PCS-SS). Results: Results revealed elevated levels of interleukin-17 and -23 in diabetic patients with Long COVID compared to those without the condition. Additionally, participants with Long COVID and diabetes reported significantly higher symptom severity across physical, psychological, and cognitive domains, as indicated by the Long COVID Severity Scale. Conclusion: These findings underscore a strong association between heightened inflammatory responses and increased Long COVID severity in diabetic individuals. Understanding these mechanisms could inform targeted interventions to improve outcomes for this vulnerable population, highlighting the importance of tailored management strategies for Long COVID in diabetics.

Paradoxical eosinophilic and cytokine responses to oral corticosteroid treatment in patients with asthma exacerbations

BackgroundThymic stromal lymphopoietin (TSLP) orchestrates eosinophilic inflammation, which may increase in asthma exacerbations. On the contrary, miR-1 inhibits TSLP-mediated eosinophil trafficking in lung endothelium. Whether the balance of TSLP and miR-1 levels determines the response to oral corticosteroids during the treatment of asthma exacerbations remains unknown. ObjectiveTo investigate the involvement of TSLP/miR-1 axis in inflammatory response to OCS treatment for asthma exacerbations. MethodsWe measured the concentrations of TSLP and other inflammatory cytokines and miR-1 expression during acute asthmatic exacerbations treated with standard oral corticosteroids (OCS) in a real-life setting. Twenty eight consecutive patients with acute asthma exacerbations treated with OCS for 1 week at the Emergency Department (ED) were studied prospectively. Steroid responders (SR) were identified by a significant reduction in blood eosinophils, whereas paradoxical responders (PR) showed no markedly decreased or even increased absolute blood eosinophil counts after OCS treatment. Differential white blood cell counts, blood cytokine levels and miR-1 expression within and between groups were compared before and after OCS treatment. The baseline cytokine concentrations in both groups were compared with those of stable asthmatics (SA). ResultsOCS treatment significantly reduced TSLP levels in steroid responders whereas this effect did not occur in paradoxical responders (P = 0.006 and P = 0.742, respectively). In contrast, miR-1 expression was unchanged in steroid responders in response to OCS, whereas it was markedly reduced in the paradoxical responders, despite higher expression at baseline compared with stable asthmatics, which may account for slower resolution of the exacerbation. ConclusionsIn some asthmatic patients with acute exacerbations who do not suppress eosinophils after a course of OCS, there is a paradoxical decrease in plasma miR-1 and increase in TSLP compared with steroid responders, which may result in slower clinical recovery.

Imprinted immune abnormalities in liver transplant patients cured of hepatitis C with antiviral drugs.

Chronic HCV infection induces interferon and dysregulates immune responses through inflammation and chronic antigenic stimulation. Antiviral drugs can cure HCV, providing a unique opportunity to examine the immunological restoration that does and does not occur when a chronic viral infection is eradicated. We quantified blood cytokines levels and used mass cytometry to immunophenotype peripheral blood mononuclear cells before and after HCV cure in 2 groups of patients and controls. At baseline, serum interferon α and soluble CD163 (a macrophage product) were elevated in both liver transplant and nonliver transplant patients compared to controls; the frequencies of several peripheral blood mononuclear cell populations differed from controls; and programmed death protein 1-positivity was increased in nearly all T cell subsets. Many abnormalities persisted after HCV cure, including elevated programmed death protein 1 expression on CD4 naïve and central memory T cells, elevated soluble CD163, and expansion of the plasmablast/plasma cell compartment. Several myeloid-lineage subsets, including Ag-presenting dendritic cells, remained dysregulated. In mechanistic studies, interferon α treatment increased programmed death protein 1 on human T cells and increased T cell receptor signaling. The data identify immunological abnormalities that persist after curative HCV treatment. Before cure, high levels of interferon α may stimulate programmed death protein 1 expression on human T cells, causing persistent functional changes.

Inflammatory Biomarkers, Cognitive Functioning, and Brain Imaging Abnormalities in Bipolar Disorder: A Systematic Review.

Recent studies have pointed to neuroinflammation and neurotrophic factors as crucial mediators in the pathophysiology origins of mood disorders. The aim of this review is to assess the potential association between cognitive impairment, brain imaging abnormalities, and inflammatory biomarkers in patients affected by bipolar disorder (BD). Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, we systematically searched PubMed, Google Scholar, Scopus, and Web of Science databases, with no year restriction, up until August 2023, for human studies that examined the relationship between inflammatory markers and cognitive impairment in BD patients. Studies based on neuroimaging, such as MRI, DTI, and fMRI, were also included, along with those examining the moderating role of specific inflammatory markers in the alteration of the brain. 59 human clinical studies satisfied the criteria for consideration. Most of the studies reviewed concur that inflammatory state, measured by peripheral blood levels of CRP and cytokines, constitutes an important contributor to cognitive impairment observed in patients with BD. Robust evidence indicates an association between cognitive impairment and CRP, IL-1RA, IL-6, and TNF-α with its receptors, whereas there is no convincing evidence for the involvement of other neuroinflammatory biomarkers. Neuroimaging studies suggest that brain structural/functional abnormalities seen in BD could also be linked to a neuroinflammatory condition. Current data provide evidence of a link between cognitive impairments observed in BD patients and mechanisms of neuroinflammation. Emerging evidence indicates that systemic inflammation might also play an important role in the deterioration of brain structures critical to cognitive functions in patients with BD. The convergence of findings across these studies strengthens our understanding of the complex neurobiological underpinnings of these disorders. Identification of BD specific inflammatory markers may be of assistance for future early therapeutic interventions.

Severe gut mucosal injury induces profound systemic inflammation and spleen-associated lymphoid organ response.

Clinical evidence indicates a connection between gut injuries, infections, inflammation, and an increased susceptibility to systemic inflammation. Nevertheless, the animal models designed to replicate this progression are inadequate, and the fundamental mechanisms are still largely unknown. This research explores the relationship between gut injuries and systemic inflammation using a Dextran Sulfate Sodium (DSS)-induced colonic mucosal injury mouse model. Continuous treatment of adult mice with 4% DSS drinking water yielded a remarkable mortality rate by day 7, alongside intensified gut injury and detectable peripheral inflammation. Moreover, RNAscope in situ hybridization with 16S rRNA probe noted bacterial penetration into deeper colon compartments of the mice following treatment with DSS for 7 days. Histological analysis revealed inflammation in the liver and lung tissues of DSS-treated mice. In addition, we found that DSS-treated mice exhibited elevation of Alanine transaminase (ALT) and Aspartate transaminase (AST) in peripheral blood and pro-inflammatory cytokine levels in the liver. Notably, the DSS-treated mice displayed a dampened metabolic profile, reduced CD45 marker expression, and an increase in apoptosis within the lymphoid organ such as spleen. These findings suggest that high-dose DSS-induced gut injury gives rise to sepsis-like systemic inflammation characterized by multiple organ injury and profound splenocyte apoptosis and dysfunction of CD45+ cells in the spleen, indicating the role of the spleen in the pathogenesis of gut-derived systemic inflammation. Together, the severe colonic mucosal injury model facilitates research into gut damage and associated peripheral immune responses, providing a vital framework for investigating mechanisms related to clinically relevant, gut-derived systemic inflammation.

Cytokines in hepatitis C-infected patients with or without opioid maintenance therapy.

Both chronic hepatitis C virus (HCV) infection and opioids cause altered blood levels of cytokines. Previous studies have investigated levels of selected groups of cytokines in patients on opioid maintenance treatment. Little is known about the levels of multiple cytokines in patients with chronic HCV infection on opioid maintenance treatment. Our aim was to investigate the cytokine profile in patients with active HCV infection with and without opioid maintenance treatment. We conducted a cross-sectional study in an out-patients population included upon referral for antiviral hepatitis C infection treatment. The level of 27 cytokines was measured in serum using multiplex technology. Patients were interviewed using a modified version of the European addiction severity index. Data pertaining to weight, height, current medication, smoking habits, allergies, previous medical history and ongoing withdrawal symptoms were collected. Non-parametric testing was used to investigate differences in levels of cytokines between the two groups. A 3-model hierarchical regression analysis was used to analyse associations between cytokines and confounding variables. Out of 120 included patients, 53 were on opioid maintenance treatment. Median duration of opioid treatment was 68.4 months. There were no demographical differences between the two groups other than age. IL-1β was lower and eotaxin-1 higher in the group on opioid maintenance treatment than in the non-opioid group. No other inter-group differences in the remaining cytokine levels were found. In HCV infection patients, the impact of chronic opioid administration on peripheral circulating cytokine level is minimal.

Proteomics-based screening of AKR1B1 as a therapeutic target and validation study for sepsis-associated acute kidney injury.

Sepsis and sepsis-associated acute kidney injury (SA-AKI) pose significant global health challenges, necessitating the development of innovative therapeutic strategies. Dysregulated protein expression has been implicated in the initiation and progression of sepsis and SA-AKI. Identifying potential protein targets and modulating their expression is crucial for exploring alternative therapies. We established an SA-AKI rat model using cecum ligation perforation (CLP) and employed differential proteomic techniques to identify protein expression variations in kidney tissues. Aldose reductase (AKR1B1) emerged as a promising target. The SA-AKI rat model received treatment with the aldose reductase inhibitor (ARI), epalrestat. Blood urea nitrogen (BUN) and creatinine (CRE) levels, as well as IL-1β, IL-6 and TNF-α levels in the serum and kidney tissues, were monitored. Hematoxylin-eosin (H-E) staining and a pathological damage scoring scale assessed renal tissue damage, while protein blotting determined PKC (protein kinase C)/NF-κB pathway protein expression. Differential proteomics revealed significant downregulation of seven proteins and upregulation of 17 proteins in the SA-AKI rat model renal tissues. AKR1B1 protein expression was notably elevated, confirmed by Western blot. ARI prophylactic administration and ARI treatment groups exhibited reduced renal injury, low BUN and CRE levels and decreased IL-1β, IL-6 and TNF-α levels compared to the CLP group. These changes were statistically significant (P<0.05). AKR1B1, PKC-α, and NF-κB protein expression levels were also lowered in the ARI prophylactic administration and ARI treatment groups compared to the CLP group (P<0.05). Epalrestat appeared to inhibit the PKC/NF-κB inflammatory pathway by inhibiting AKR1B1, resulting in reduced inflammatory cytokine levels in renal tissues and blood. This mitigated renal tissue injuries and improved the systemic inflammatory response in the severe sepsis rat model. Consequently, AKR1B1 holds promise as a target for treating sepsis-associated acute kidney injuries.

Functional status of patients after myocardial revascularization combined with chronic low back pain at the sanatorium-resort stage of medical rehabilitation

To develop an algorithm for assessing the functional status of patients after myocardial revascularization with chronic low back pain. The single-center cross-sectional cohort study (September 2021 - May 2022 yrs) included 50 patients after a myocardial revascularization with chronic low back pain (36 women, 14 men; median age 63.5 [55.5; 67.5] years), who were the study group and 10 patients with CIHD (5 women, 5 men; median age 65.0 [62.0; 68.0] years) who joined the control group. All patients underwent clinical (neurological and therapeutic examination), functional (clinical tests, echocardiography) and laboratory (general and biochemical blood analysis, blood cytokine levels) investigations, the functional class of impairment was defined. There are 4 groups with combined pain syndrome (cardiogenic and vertebrogenic) in different ratios due to different functional and laboratory status among patients after the myocardial revascularization with chronic back pain. The presence of cardiogenic pain syndrome was associated with an increase in leukocyte and peripheral blood glucose levels, interleukin-6, myocardial mass enlargement, while vertebrogenic pain syndrome correlated with personal anxiety. The evaluation of the functional status of patients according to the degree of severity of cardiogenic and vertebrogenic pain syndrome has revealed a simple method of pathogenetically based differentiation selection for individual rehabilitation program of patient development.

Ремиссия и иммунологический профиль пациентов на начальных стадиях шизофрении

Aim. To study the types of remission and levels of peripheral inflammatory cytokines as potential biomarkers of remission in patients at the early stages of schizophrenia. Design. A naturalistic study. Materials and methods. Forty-eight patients (25 women and 23 men) were examined at the initial stages of schizophrenia during the period of remission (age — 28.3 ± 5.8 years). The duration of the disease was 2.7 ± 1.3 years, the average age of disease onset — 25.8 ± 5.5 years. The average number of relapses reached 1.8 ± 0.7. 19 (40%) of patients had one psychotic episode in their anamnesis, 24 (50%) — two, 5 (10%) — three. The control group included 86 people, 38 men and 48 women, aged 18 to 30 years without mental, autoimmune disorders, exacerbation of chronic somatic diseases (standard relatively healthy group, the level of proinflammatory cytokines in participants tended to zero). The study used a clinical and psychopathological method and a standardized assessment using the Positive and Negative Syndrome Scale (PANSS). Results. The average duration of remission was 11.4 months. In the early stages of schizophrenia, the paranoid type of remission was predominant (48%). The thymopathic type of remission occurred in 18% of cases, apathetic and hypochondriacal — 10% each, pseudopsychopathic — in 8%, asthenic — in 6%. General psychopathological symptoms were most pronounced in hypochondriacal, residual negative symptoms — in the apathetic type of remission. In the hypochondriacal type, the severity of positive and negative symptoms did not differ, and in the paranoid type, residual positive symptoms prevailed over negative ones. The thymopathic type of remission was distinguished by the least severity of residual symptoms. In 70% of patients in the early stages of schizophrenia, a significant increase in blood cytokine levels was found compared to those in the control group. The levels of interleukins (IL) 6, IL-9, IL-10, IL-13, IL-22, tumor necrosis factor α, CCL20/MIP3-α increased to the greatest extent (p = 0.001). The level of IL-22 correlated with the total PANSS score (r = –0.52; p = 0.008), and the level of IL-6 — with the composite PANSS index (the difference between the sum of the scores of positive and negative symptoms) (r = 0.46; p = 0.022). The strongest cytokine reaction was observed in the paranoid and pseudopsychopathic variants due to an increase in the content of IL-6, IL-33 and IL-13. The longer the duration of the present remission, the lower were the levels of IL-33 (r = –0.45; p = 0.023), IL-17A (r = –0.40; p = 0.049), IL-17F (r = –0.59; p = 0.002). Conclusion. The available data indicate an important role of cytokines in the development of schizophrenia. The presented results may have prognostic value for assessing the stability of remission, the studied cytokines — serve as potential biomarkers of schizophrenia remission and therapeutic targets for pathogenetic therapy. Keywords: schizophrenia, first psychotic episode, remission, cytokines.

STING-STAT6 Signaling Pathway Promotes IL-4+ and IFN-α+ Fibrotic T Cell Activation and Exacerbates Scleroderma in SKG Mice.

Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4+ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast. Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4+ T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4+ T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.

Endoplasmic Reticulum Stress and Obesity.

In recent years, the world has seen an alarming increase in obesity and is closely associated with insulin resistance, which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) plays in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably many causes for obesity-related insulin resistance and inflammation. One of the faulty mechanisms is protein homeostasis, protein quality control system included protein folding, chaperone activity, and ER-associated degradation leading to endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens, or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.

Evaluating Biomarkers for Predicting Clinical Outcomes in COVID-19 Patients: A Systematic Review

The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel human pathogen severe acute respiratory syndrome coronavirus 2, that resulted in millions of human deaths worldwide. A systematic review was conducted to identify biomarkers associated with the clinical progression of COVID-19. The search was conducted across four databases (ProQuest, PubMed, Scopus, and Web of Science) for articles published between 2020 and 2022, with 735 peer-reviewed papers identified. After screening for duplicates and relevance, 87 articles were included in this systematic review. The selected articles included various inflammatory, haematological, hepatic, respiratory, cardiac and other clinical biomarkers that were used to predict the severity and mortality risk in COVID-19 patients. In hospitalised COVID-19 patients, the blood levels of specific cytokines and chemokines were significantly higher, including pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, IL-18, and tumour necrosis factor, as well as chemokines like interferon gamma-induced protein 10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1 alpha. The levels of the anti-inflammatory cytokine IL-10 were also found to be higher, while elevated levels of C-reactive protein, procalcitonin, and ferritin in COVID-19 patients were related to the increased severity and mortality risk of the disease. Growth/differentiation factor 15 and beta-2 microglobulin were also useful biomarkers and independent risk factors for death in COVID-19 patients. The review revealed clinical biomarkers that can be used as indicators of COVID-19 disease progression and are critical to timely interventions. Understanding the clinical picture associated with biomarker profiles is necessary for future improved COVID-19 management strategies and therapeutic approaches.

Lactiplantibacillus plantarum HY7718 Improves Intestinal Integrity in a DSS-Induced Ulcerative Colitis Mouse Model by Suppressing Inflammation through Modulation of the Gut Microbiota.

Inflammatory bowel disease (IBD), a chronic condition that causes persistent inflammation in the digestive system, is closely associated with the intestinal microbiome. Here, we evaluated the effects of Lactiplantibacillus plantarum HY7718 (HY7718) on IBD symptoms in mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration of HY7718 led to significant improvement in the disease activity index score and the histological index, as well as preventing weight loss, in model mice. HY7718 upregulated the expression of intestinal tight junction (TJ)-related genes and downregulated the expression of genes encoding pro-inflammatory cytokines and genes involved in the TLR/MyD88/NF-κB signaling pathway. Additionally, HY7718 reduced the blood levels of pro-inflammatory cytokines, as well as reversing DSS-induced changes to the composition of the intestinal microbiome. HY7718 also increased the percentage of beneficial bacteria (Lactiplantibacillus and Bifidobacterium), which correlated positively with the expression of intestinal TJ-related genes. Finally, HY7718 decreased the population of pathogens such as Escherichia, which correlated with IBD symptoms. The data suggest that HY7718 improves intestinal integrity in colitis model mice by regulating the expression of TJ proteins and inflammatory cytokines, as well as the composition of the intestinal microflora. Thus, L. plantarum HY7718 may be suitable as a functional supplement that improves IBD symptoms and gut health.

The links between neuroinflammation, brain structure and depressive disorder: A cross-sectional study protocol.

It is known that symptoms of major depressive disorder (MDD) are associated with neurodegeneration, that lipopolysaccharide (LPS) can induce symptoms of MDD, and that blood LPS levels are elevated in neurodegeneration. However, it is not known whether blood LPS and cytokine levels correlate with MDD, cognition and brain structure, and this is tested in this study. This cross-sectional study includes individuals with MDD (n = 100) and a control group of individuals with no one-year history of a mental disorder (n = 50). A comprehensive evaluation is performed, including the collection of basic sociodemographic information, data on smoking status, body mass index, course of MDD, past treatment, comorbid diseases, and current use of medications. Diagnosis of MDD is performed according to the WHO's [2019] International Classification of Diseases and related health problems by psychiatrist and severity of MDD is evaluated using the Montgomery-Åsberg Depression Scale. The Cambridge Neuropsychological Test Automated Battery is used to evaluate cognitive functioning. Venous blood samples are taken to measure genetic and inflammatory markers, and multiparametric brain magnetic resonance imaging is performed to evaluate for blood-brain barrier permeability, structural and neurometabolic brain changes. Descriptive and inferential statistics, including linear and logistic regression, will be used to analyse relationships between blood plasma LPS and inflammatory cytokine concentrations in MDD patients and controls. The proposed sample sizes are suitable for identifying significant differences between the groups, according to a power analysis. Trial registration: Clinicaltrials.gov NCT06203015.

IMMUNOINFLAMMATORY PROCESSES IN THE PATHOGENESIS OF ATHEROSCLEROSIS

HighlightsThe article describes the main pathogenetic aspects of atherogenesis and focuses on the role of low-intensity inflammation in this process. Moreover, the article presents data on the possibilities of predicting cardiovascular outcomes in patients using a number of pro-inflammatory markers, and on the effectiveness of anti-inflammatory therapy in this cohort of patients. AbstractChronic low-intensity inflammation is currently considered one of the most significant risk factors for cardiovascular disease. The initiation and progression of atherosclerosis are associated with an inflammatory response to endothelial damage, accompanied by an increase in number of pro-inflammatory markers blood circulation. The atherogenic effect of the main risk factors for atherosclerosis, such as hypertension, smoking, increased dietary fat intake, physical inactivity and obesity, as well as psychological and emotional factors and sleep disturbance, is mostly carried out through these mechanisms. In addition, proinflammatory cytokines blood levels increase is associated with sympathetic tone level increase under these risk factors influence.The article describes the relevant atherogenesis mechanisms and the results of large clinical trials studying the relationship between inflammatory activity, assessed by the levels of various pro-inflammatory markers, and the risk of cardiovascular complications. Data regarding the use of anti-inflammatory drugs such as canakinumab, anakinra, tocilizumab, colchicine to treat patients with coronary artery disease are given. The efficacy of nano-immunotherapy, when powerful anti-inflammatory agents are target delivered to atherosclerotic plaques using nanoparticles, is considered, as well as the anti-inflammatory effect of renal denervation due to the sympatholytic activity of this procedure.

Ganoderma lucidum spore oil synergistically enhances the function of cyclophosphamide in the prevention of breast cancer metastasis.

Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and interleukin (IL)-6 cytokine levels in mouse blood, whereas also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.