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BACKGROUND The development and progression of prostate cancer are multistep processes involving several growth factors, hormones, and cytokines. This study aimed to measure the serum concentrations of different cytokines and determine their correlation with prostate-specific antigen (PSA) levels and disease grade in patients with prostate adenocarcinoma. MATERIAL AND METHODS This cross-sectional study was conducted from March 2023 to March 2024 at the Clinic of Oncology of the University Hospital Center in Mostar, Bosnia and Herzegovina. Altogether, 50 male patients with prostate adenocarcinoma were included, of whom 28 had no proven metastases (PC group) and 22 had metastatic disease (MPC group). Serum concentrations of total (tPSA), free (fPSA), and complexed (cPSA) PSA were determined using a chemiluminescent microparticle immunoassay, whereas serum concentrations of cytokines were measured using a flow cytometry bead-based assay. RESULTS The MPC group had higher serum tPSA, fPSA, and cPSA levels than the PC group. The PC group had significantly higher serum levels of monocyte chemotactic protein (MCP)-1 than the MPC group (P=0.008). In the PC group, serum levels of interleukin (IL)-10 significantly correlated with cPSA. In the MPC group, serum concentrations of IL-1ß, tumor necrosis factor (TNF)-alpha, and IL-23 significantly correlated with disease grade. CONCLUSIONS Our study emphasizes the importance of MCP-1 in the development of prostate cancer, while IL-10 was the only cytokine whose serum level significantly correlated with cPSA. Serum concentrations of IL-1ß, TNF-alpha, and IL-23 may serve as potential biomarkers for disease grade.

Circulating extracellular vesicles (EVs) have been associated with the development of COVID-19 due to their roles in viral infection, inflammatory response, and thrombosis. However, the direct induction of lung inflammation by circulating EVs from severe COVID-19 patients remains unknown. EVs were extracted from the plasma of severe COVID-19 patients admitted to intensive care and healthy controls. To study the effect of COVID-19 EVs on lung inflammation, mice were intratracheally instilled with EVs. To examine the proinflammatory effects of EVs in vitro , bone marrow-derived macrophages were treated with EVs. COVID-19 but not control EVs triggered lung inflammation, as assessed by total protein level, total cell count, neutrophil count, and levels of proinflammatory cytokines in the bronchoalveolar lavage. COVID-19 EVs also promoted M1 polarization of alveolar macrophages in vivo . Treatment of bone marrow-derived macrophages with COVID-19 EVs enhanced the M1 phenotype and augmented the production of IL-1β, IL-6, and TNF-α. In summary, circulating EVs from severe COVID-19 patients induce lung inflammation in mice. EVs could become a potential therapeutic target for alleviating lung injury in COVID-19., Importance: Extracellular vesicles (EVs) have been reported to facilitate cytokine storm, coagulation, vascular dysfunction, and the spread of the virus in COVID-19. The direct role of circulating EVs from severe COVID-19 patients in lung injury remains unrecognized. Our study demonstrated that plasma EVs obtained from severe COVID-19 patients induced lung inflammation and polarization of alveolar macrophages in vivo . In vitro experiments also revealed the proinflammatory effects of COVID-19 EVs. The present study sheds fresh insight into the mechanisms of COVID-19-induced lung injury, highlighting EVs as a potential therapeutic target in combating the disease., Competing Interests: The authors declare no conflict of interest.

Persistent inflammation during chronic human immunodeficiency virus (HIV) infection may affect the immune response against severe acute respiratory syndrome-coronavirus 2 (SARS- CoV-2) infection. Plasma levels of multiple proinflammatory cytokines during acute SARS-CoV-2 infection were measured in people with HIV (PWH) with effective combination antiretroviral therapy. There were no significant differences in any of the measured cytokines between severity levels of coronavirus disease 2019 (COVID-19) in PWH, while most were significantly higher in HIV-uninfected individuals with severe COVID-19, suggesting that excess cytokines release by hyperinflammatory responses do not occur in individuals with severe COVID-19 with HIV infection. The strong associations between the cytokines observed in HIV-uninfected individuals, particularly between IFN-α/TNF-α and other cytokines, were lost in PWH. The steady-state plasma levels of IP-10, ICAM-1, and CD62E were significantly higher in PWH, indicating that they were in an enhanced inflammatory state. The absence of several inter-cytokine correlations was observed in in vitro lipopolysaccharide stimulus-driven cytokine production in PWH. These data suggest that inflammatory responses during SARS-CoV-2 infection in PWH are distinct from those in HIV-uninfected individuals, partially because of the underlying inflammatory state and/or impairment of innate immune cells.

Background: Major depressive disorder (MDD) and schizophrenia (SCH) are common and severe mental disorders that are mainly diagnosed depending on the subjective identification by psychiatrists. Finding potential objective biomarkers that can distinguish these two diseases is still meaningful., Methods: In the present study, we investigate the differences in plasma inflammatory cytokines and short-chain fatty acids (SCFAs) among patients with MDD (n = 24) and SCH (n = 24), and gender- and age-matched healthy controls (HC, n = 27) and identify potential plasma biomarkers., Results: We found that the concentrations of pro-inflammatory cytokines were increased, whereas the anti-inflammatory cytokines were decreased in both MDD and SCH. Meanwhile, except for an increase in 4-Methylvaleric acid, other SCFAs with statistical differences were reduced in both MDD and SCH. Moreover, potential biomarker panels were developed that can effectively discriminate MDD from HC (AUC = 0.997), SCH from HC (AUC = 0.999), and from each other (MDD from SCH, AUC = 0.983)., Conclusions: These data suggest that alterations in plasma cytokines and SCFAs might be one of the potential features for distinguishing MDD and SCH., Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100051243, registration date: 2021/09/16., Competing Interests: Declarations. Ethics approval and consent to participate: The research was registered in the Chinese Clinical Trial Registry (number: ChiCTR2100051243, 16th September 2021) and its protocol was approved by the China Registered Clinical Trial Ethics Review Committee (number: ChiECRCT20210335). All subjects voluntarily participated in this research and provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Role of the funding source: We thank our financial sponsors for providing the fees for the analysis of plasma fatty acids and inflammatory cytokines for this study and the page charges for the publication of the article., (© 2024. The Author(s).)

Disrupted cytokine networks and autoantibodies play an important role in the pathogenesis of systemic lupus erythematosus. However, conflicting reports and non-reproducibility have hindered progress regarding the translational potential of cytokines in SLE. This study attempts to address the existing knowledge gap using multiplex cytokine assay and machine learning. 67 SLE patients fulfilling SLICC criteria were recruited after informed consent, and circulating cytokines were measured by multiplex cytokine assay kit. We observed a positive association between actual disease activity scores (SLEDAI) and predicted scores from a partial least squares regression (PLSR) analysis of multivariate cytokine response data, with MIP-1α having a strong contribution towards disease activity. Our analysis also highlights increased IL-12 as a potential biomarker in nephritis and elevated MIP-1α as a signature of NPSLE. Using a k-Modes clustering algorithm to stratify patients based on patterns of co-occurrence of circulating autoantibodies, we identified 4 distinct clusters of patients. All 4 clusters had patients with nephritis, but patients in cluster 3 with nephritis were characterised by low levels of housekeeping and homeostatic cytokines and the presence of anti-Ro antibodies, which is a novel observation. Thus, we demonstrate that cytokines can be a surrogate to predict disease activity and organ involvement in SLE. Moreover, we show the utility of unsupervised machine learning algorithms using specific autoantibody signatures to predict renal involvement in SLE., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare that no competing interests exist., (© 2024. The Author(s).)

Introduction: 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., Methods and Analysis: 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., Administrative Information: Trial registration: Clinicaltrials.gov NCT06203015., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Milasauskiene et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The systemic and local inflammatory response in patients after surgical operation is closely related to the quality of the wound healing. Low-quality wound healing and defects in the suture technique lead to the occurrence of incisional hernia (IH). However, the causal relationship between human circulating inflammatory cytokines, immune cell traits, and the risk of IH remains unclear., Methods: We used summary data from genome-wide association studies to assess the causal relationship between 91 types of circulating inflammatory factors, 731 types of circulating immune cell traits, and the risk of IH. The outcome dataset was obtained from FinnGen, including 6,336 patients with IH and 232,612 controls. We performed Mendelian Randomization (MR) analysis to identify their causal relationship and immune cell phenotypes upstream of inflammatory factors. Inverse variance weighting is considered to be the main analysis method., Results: Among the identified cytokines, TNF-related activation-induced cytokine levels were associated with a lower risk of IH (OR: 0.89; 95% CI: 0.82-0.96; P = 0.003). In contrast, interleukin-5 levels were associated with an increased risk of IH (OR: 1.18; 95% CI: 1.06-1.31; P = 0.003). Additionally, a significant causal relationship was found between four immune cell traits and the risk of IH (P < 0.01). Through two-step MR analysis, we determined that interleukin-5 levels mediate the causal relationship between the relative count of CD25hi % CD4 + in Treg cells and the higher risk of IH., Conclusion: This study found a causal relationship between specific inflammatory cytokines, immune cell traits, and risk of IH. These results can help surgeons predict the risk of IH and take preventive measures., Competing Interests: Declarations. Ethical approval and informed consent: Not applicable. All datasets used for analysis are publicly available. Ethical approval and informed consent are also fully qualified by the institution-uploaded corresponding data. Competing interests: There are no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Long Covid results from the damage caused by SARS-CoV-2, involving the release of cytokines and the continuous activation of immune cells. This cross-sectional study investigates leukocyte and cytokine profiles in Long Covid patients in the Amazon, a region where such studies are limited. Blood samples were analysed for differential leukocyte counts and cytokine levels. We suggest elevated lymphocyte counts in hospitalised patients and those with severe COVID-19. Higher eosinophil counts were observed in patients with up to three months of Long Covid, and increased monocyte counts in those with up to six months. IL-2 levels were higher in patients with fewer symptoms and Long Covid duration of more than three months, whereas IL-10 may remain elevated for up to 12 months. We suggest positive correlations between neutrophils, monocytes, eosinophils, and lymphocytes with different cytokines (IFN-γ, IL-6, IL-4, IL-17a, IL-2). Women were associated with lower hospitalisation rates and longer durations of Long Covid; increased lymphocyte counts were linked to hospitalisation due to COVID-19, while higher monocyte counts were associated with Long Covid durations of up to six months. We suggest that Long Covid patients may exhibit alterations in inflammatory markers, indicating a persistently pro-inflammatory microenvironment that tends to diminish after 12 months of Long Covid., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Propionic and methylmalonic acidemias (PAcidemia and MMAcidemia, respectively) are genetic disorders characterized by acute metabolic decompensation and neurological complications. L-carnitine (LC) is effective in reducing toxic metabolites that are related to the pathophysiology of these diseases. Therefore we investigated biomarkers of inflammation (cytokines and C-reactive protein (CRP)), neurodegeneration (BDNF, NCAM-1 and cathepsin-D) and biomolecules oxidation (sulfhydryl content and thiobarbituric acid-reactive species (TBARS)), as well as carnitine concentrations in untreated patients with PAcidemia and MMAcidemia, in patients under treatment with LC and a protein-restricted diet for until 2 years and in patients under the same treatment for more than 2 years. It was verified an increase of CRP, IL-6, IL-8, TNF-α, IL-10, NCAM-1 and cathepsin-D in untreated patients compared to controls. On the other hand, reduced levels of TNF-α, CRP, IL-10, NCAM-1 and cathepsin-D were found in plasma from treated patients, as well as increased concentrations of LC. Furthermore, oxidative biomarkers were increased in untreated patients and were normalized with the prolonged treatment with LC. In conclusion, this work shows, for the first time, that inflammatory and neurodegenerative peripheral biomarkers are increased in patients with PAcidemia and MMAcidemia and that treatment with LC is effective to protect against these alterations., Competing Interests: Declarations Ethics approval This study was approved by the Ethics Committee of Hospital de Clínicas de Porto Alegre, RS, Brazil, and the informed consent was obtained according to the guidelines of the committee (Project number 20230157). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Consent to participate Informed consent was obtained from all patients for being included in the study. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Immune dysregulation has been identified as a contributing factor in the pathophysiology of schizophrenia. This study aimed to investigate variations in specific immune regulators and their correlation with psychopathology and cognitive functions in male patients with chronic schizophrenia., Methods: Employing a cross-sectional design, this study included 72 male patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status were utilized to assess psychopathology and cognitive functions, respectively., Results: Serum levels of interleukin (IL)-4, IL-10, IL-12p40, IL-13, and monocyte chemoattractant protein-1 (MCP-1) were measured. There were significantly increased levels of IL-4, IL-13, and MCP-1, alongside decreased levels of IL-10 in patients compared to controls (all P < 0.05). IL-4 levels showed a significant negative association with PANSS positive symptoms (beta=-0.222, P = 0.042). After controlling for antipsychotic medication, BMI, and smoking, this correlation was no longer significant (r=-0.232, P = 0.055). Additionally, positive correlations of IL-4 (beta = 0.297, P = 0.008), IL-13 (beta = 0.371, P = 0.001), and MCP-1 (beta = 0.280, P = 0.013) with language scores were observed. Increased levels of IL-4 (P = 0.044, OR = 1.994), IL-13 (P = 0.019, OR = 2.245), as well as IL-4 and MCP-1 interactions (P = 0.043, OR = 2.000) were positively associated with the risk of chronic schizophrenia, while lower levels of IL-10 (P = 0.003, OR = 0.2.867) were also linked to an increased risk., Conclusion: The identified associations between specific immune markers and the clinical and cognitive features of chronic schizophrenia in males underscored the potential immune-mediated mechanisms underlying schizophrenia., Competing Interests: Declarations Ethical approval and consent to participate We declare that all experiments on human subjects were conducted in accordance with the Declaration of Helsinki and that all procedures were carried out with the adequate understanding and written consent of the subjects. All experimental protocols were approved by the Ethics Committee of Lian Yun Gang Fourth People’s Hospital. Informed consent was obtained from all the participants and/or their legal guardians. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The impact of Pseudomonas aeruginosa (PA) was explored in a mouse model with non-diarrheal gut permeability defect using 1.5% dextran sulfate solution (DSS) plus antibiotics (ATB) with or without orally administered PA. As such, ATB+DSS+PA mice induced more severe intestinal injury as indicated by stool consistency and leaky gut (FITC-dextran assay, bacteremia, and endotoxemia) with an increase in serum cytokines, liver enzyme, and hepatocyte apoptosis when compared with ATB+DSS mice. There was no abnormality by these parameters in the non-DSS group, including water alone (control), antibiotics alone (ATB+water), and antibiotics with PA (ATB+water+PA). Despite a similarly fecal microbiome patterns between ATB+DSS and ATB+DSS+PA groups, a higher abundance of Pseudomonas, Enterococci, and Escherichia-Shigella was detected in ATB+DSS+PA mice. Additionally, the additive pro-inflammation between pathogen molecules, using heat-killed P. aeruginosa preparations, and LPS against enterocytes (Caco2) and hepatocytes (HegG2), as indicated by supernatant IL-8 and expression of several genes (IL-8, NF-kB, and NOS2) are demonstrated. In conclusion, presence of P. aeruginosa in the gut exacerbated DSS-induced intestinal injury with spontaneous translocation of LPS and bacteria from the gut into the blood circulation (leaky gut) that induced more severe systemic inflammation. The presence of pathogenic bacteria, especially PA in stool of the healthy individuals might have some adverse effect. More studies are in needed., Competing Interests: The authors declare no conflict of interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2024 Panpetch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: High fructose consumption increases blood pressure through microglia-related neuroinflammation in rats. Since intermediate-conductance calcium-activated potassium channels (KCa3.1) potentiates microglial reactivity, we examined whether the pretreatment with the KCa3.1 channel blocker TRAM-34 or minocycline prevents hypertension development in fructose-fed rats., Methods: The study involved male Wistar rats that were given either high fructose (10% in drinking water) or tap water for 21 days. Fructose groups also received minocycline or TRAM-34 systemically for 21 days. We measured systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) periodically with tail-cuff; proinflammatory cytokines, and insulin levels in plasma via Enzyme-linked immunosorbent assay (ELISA), and neuroinflammatory markers in the nucleus tractus solitarii (NTS) by qPCR at the end of 21 days. We also examined endothelium-dependent hyperpolarization (EDH)-type vasorelaxations in isolated mesenteric arteries of the rats ex vivo., Results: SBP, DBP, and HR increased in the fructose group. Both minocycline and TRAM-34 significantly prevented these increases. Fructose intake also increased plasma interleukin-6, interleukin-1β, tumor necrosis factor-α, and insulin levels, whereas pretreatment with TRAM-34 prevented these increases as well. Iba-1, but not cluster of differentiation-86 levels were significantly higher in the NTS samples of fructose-fed hypertensive rats which implied microglial proliferation. EDH-type vasorelaxations mediated by endothelial KCa3.1 attenuated in the fructose group; however, TRAM-34 did not cause further deterioration in the relaxations., Conclusions: TRAM-34 is as effective as minocycline in preventing fructose-induced hypertension without interfering with EDH-type vasodilation. Furthermore, TRAM-34 relieves high fructose-associated systemic inflammation., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients., Methods: 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed., Results: TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P = 0.79). TL was significantly negatively associated with age (β = -0.007, P < 0.001). In addition, log TNF-α levels were significantly negatively associated with TL (P = 0.009), in both the BD patients (P = 0.02) and HCs (P = 0.05)., Conclusion: We found a significant association between TNF-α levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 h of intubation and again at 72 h post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients with higher SARS-CoV-2 viral loads in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. These findings provide novel insights into the underlying mechanisms of VAP, with potential implications for management and prevention., Competing Interests: Declarations Competing interests The authors declare that they have no competing interests. Ethical approval and consent to participate The protocol and informed consent were developed by the Translational Science in Infectious Diseases and Critical Care Medicine (TSID-CCM) research group from Universidad de La Sabana. These were reviewed and authorized by the Institutional Review Board/Independent Ethics Committee (IRB/EC) of the participating institutions. Ethical supervision ensured that informed consent was obtained from all study participants or their authorized representatives. All patients provided informed consent to participate (CUS-20190903)., (© 2024. The Author(s).)

Background: Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions., Methods: Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman's correlation networks distinguishing BPD and severe ROP patients from non-affected were created., Results: Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted., Conclusions: Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Regional Ethical Board, Gothenburg (Dnr 303–11) (Clinical trial NCT02760472). Children were enrolled in the study following parental written informed consent. Consent for publication Not applicable. Competing interests Ann Hellström holds stocks in Premalux AB, a company with financial interest in IGF-I treatment of preterm infants. In addition, Ann Hellström, has received consulting fees from Takeda., (© 2024. The Author(s).)

Objective: The aim of this study was to assess the dietary pattern of healthy adult and adolescent women, pregnant and non-pregnant, and relate this profile to clinical and laboratory characteristics., Methods: A prospective cohort study was carried out with 40 women who met the selection criteria: 10 non-pregnant adults, 10 pregnant adults, 10 non-pregnant adolescents, and 10 pregnant adolescents. Dietary data were collected using a registration form, a 24-h recall, and a food frequency questionnaire. Serum levels of interleukin 6 and tumor necrosis factor α were determined by capture ELISA., Results: The majority of women were married (22.5%), had completed high school (57.5%), and were white (47.5%). Overall, only one (10%) pregnant adult reported smoking. Dietary supplement use was reported by eight (80%) pregnant adults, four (40%) pregnant adolescents, two (20%) non-pregnant adolescents, and no non-pregnant adults. Pregnant adolescents had a higher intake of omega-3 when compared to pregnant adults and non-pregnant adults (p=0.01 and 0.02, respectively). Pregnant adolescents consumed less minimally processed foods than pregnant adults, non-pregnant adults, and non-pregnant adolescents (p=0.008, 0.019, and 0.024, respectively). Serum levels of tumor necrosis factor α and interleukin 6 did not show statistical differences among the four groups (p=0.229 and 0.440, respectively)., Conclusions: The dietary patterns of healthy adult and adolescent women, whether pregnant or not, were similar, with pregnant adolescents having a higher intake of omega-3. Pregnant adolescents ate less in natura (minimally processed) food than all the other women.

Background: Alterations in haematological, biochemical parameters and cytokine levels, were reported in patients with COVID-19, however, there is an underrepresentation of the African population, which could provide evidence for understanding SARS-CoV-2 pathogenesis and useful tools for clinical management of cases. In this study, we aimed to determine the haematological, biochemical and cytokine profile in Mozambican individuals with SARS-CoV-2., Methods: A cohort of 85 Mozambican individuals with RT-PCR SARS-CoV-2 results, was stratified into negative, asymptomatic, mild, moderate, and severe categories. Haematological, biochemical and cytokines measurement were performed on samples from the study participants. Principal component analysis (PCA) was performed to identify similar patterns among the study cases. Comparisons between groups were performed using the Kruskal-Wallis test. Receiver operating characteristic (ROC) and area under the curve (AUC) analysis were conducted to evaluate the ability of these parameters to distinguish severe from non-severe cases of SARS-CoV-2 infection., Results: SARS-CoV-2 infection was associated with a significant (p < 0.05) decrease in peripheral blood absolute counts of total lymphocytes and eosinophils, below the reference values along with no abnormal change (p > 0.05) in red blood cell count, haemoglobin, platelets and other red series parameters. At the serum level, SARS-CoV-2 infection was associated with an increase in serum levels of C-reactive protein (C-RP) and glucose above the reference values and to a significant reduction a significant (p < 0.05) reduction in levels of interferon-gamma (INF-γ), Tumour Necrosis Factor alfa (TNF-α) and the interleukin 1 beta (IL-1β) and IL-6 in severe cases, when compared to negative cases. Haematological, biochemical and cytokine profiles segregate severe from non-severe cases of COVID-19 with an excellent performance of C-RP (AUC = 0.95; p < 0.001) and good performance of lymphocytes (AUC = 0.88; p < 0.001) and IL-15 (AUC = 0.86; p < 0.001)., Conclusion: The lack of variation in red and platelet series, coupled with a decrease in the levels of classical pro-inflammatory in severe cases, deviates from what has been reported in other contexts suggesting, that there may be peculiarities in COVID-19 manifestation within the context of this study population. Furthermore, these results identify parameters with potential for clinical management of COVID-19 and therefore good resource allocation, particularly for severe cases., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the National Bioethics Committee for Health (CNBS), and the Ministry of Health (MISAU) of Mozambique (Ref.668/CNBS/20). Written informed consent was obtained from each participant prior of conducting any study procedures. For hospitalized patients, if they were unable to give consent, a family member gave informed consent for them. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Tuberculosis (TB) and HIV co-infections are extensively overlapping, especially in developing countries. HIV infection is known as a major risk factor for the reactivation of latent TB into active TB. Although not fully understood and needs further study, HIV infection might enhance the reactivation of latent TB by breaching immune control mechanisms. We investigated the influence of HIV infection on the cytokine response of LTB-infected individuals. Heparinized venous blood was collected from 40 ART-naïve HIV-infected and 30 HIV-negative healthy controls for LTB screening, plasma collection, and PBMC isolation and stimulation. The level of cytokines in plasma and their production by PBMCs stimulated with purified protein derivative (PPD), staphylococcus enterotoxin B (SEB), or unstimulated PBMCs were analyzed using a cytometric bead array (CBA) assay. PPD-induced IL-2 by PBMCs was higher in LTB-infected groups compared with HIV-negative LTB-negative groups (p = 0.0015). When LTB-infected groups were co-infected with HIV (HIV+LTB+), the IL-2 (p < 0.0001) and IFN-gamma (p = 0.0144) production by PPD-stimulated PBMCs was reduced. The level of IL-2 (p = 0.0070), IL-6 (p = 0.0054), and TNF-alpha (p = 0.0045) in plasma were lower in HIV+LTB+ individuals compared with HIV-negative LTB-positive (HIV-LTB+) groups. Our findings suggested that HIV co-infection in LTB-positive individuals is associated with the diminished production of PPD-induced Th1 (IFN-gamma and IL-2) cytokines by PBMCs and in the plasma level of IL-2 and proinflammatory cytokines (IL-6 and TNF-alpha)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Girmay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Immunopathology of human tuberculosis (TB) in a subgroup of patients is characterized by aberrantly high concentrations of inflammatory cytokines, for example Interleukin (IL)-6. Concomitant (co-)infections by parasites can affect host immunity, but the impact on immunopathology in TB patients is poorly defined. Here we characterized a group of patients with TB ( n = 76) from Ghana with different protozoan and helminth co-infections. Plasma cytokines were measured at the onset of disease and anti-mycobacterial treatment efficacy was monitored during disease course. A subgroup of TB patients had co-infections with protozoan (n = 19) or helminth (n = 16) parasites. Plasma analyses for candidate cytokines identified lower levels of IL-6 in parasite co-infected patients with TB. Moreover, it took less time for co-infected patients to become sputum-negative for Mycobacterium tuberculosis during treatment. These results indicated an influence of parasite co-infections on immunopathology in TB and suggested positive effects on treatment efficacy., (© 2024. The Author(s).)

To investigate the degrees of EB virus reactivation in patients with inflammatory bowel disease (IBD) treated with different biologics and the levels of important cytokines associated with relapse under the influence of this virus, and to assess its diagnostic efficacy as a risk factor for identifying disease relapse. A case-control retrospective study based on patients' hospitalization history data was conducted to select a total of 105 patients who were hospitalized in the Department of Gastroenterology, Huashan Hospital, Fudan University, with a confirmed diagnosis of IBD from 2021 to 2023. Based on the quantitative copy level of whole blood EBV DNA to determine the status of EB virus infection in patients, integrated cytokine 8 (IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17, TNF-α, IFN-γ), C-reactive protein, and fecal calreticulin, to find the risk variable associated with treatment relapse. Logistic regression was used to analyze the relative risk between this variable and treatment relapse, and ROC curves were used to predict the diagnostic efficacy of cytokine multifactorial thresholds for treatment relapse. Results showed that the median age of the study was 37(26, 54)years, with a minimum of 18 years and a maximum of 70 years, with a median age of 34(24, 51) years for Crohn's Disease (CD) patients and 46(35, 60) years for Ulcerative colitis (UC) patients, with a statistically difference between the ages of the two groups ( t =2.675, P =0.009). The median age at 50 years of patients treated with Vedolizumab (VDZ) in the UC group was higher than in the treatment groups other than VDZ. The highest rate of EB virusreactivation was found in the group treated with immunosuppressants Azathioprine (AZA) combined with anti-tumor necrosis factor-α (anti-TNF-α) and VDZ (62.5% in both groups), and the lowest in the group treated with Ustekinumab (UST) (0%). IL-2 levels were elevated in the AZA+anti-TNF-α and anti-TNF-α groups after EB virus entryreactivation. Three treatment groups, AZA+anti-TNF-α, anti-TNF-α, and VDZ, had elevated levels of IL-6 expression after EB virus entry reactivation.In the anti-TNF-α treatment-related group IL-2was associated with treatment relapse in IBD ( OR =1.127, 95% CI: 1.044-1.256, P =0.007). ROC analysis showed that the AUC for IL-2 combined with EB virus in a replicative state was 0.8282 ( P =0.006), with a negative predictive value and a positive value of 90% and 75%, respectively. As well as IL-6 was associated with treatment relapse of IBD in the anti-TNF-αtreatment-related group as well as in the VDZ-treated group ( OR =1.049, 95% CI: 1.017-1.095, P =0.008). ROC analysis showed that the diagnostic sensitivity and specificity for post-treatment relapse at a critical value of 6.10 pg/ml for IL-6 was 83.33% and 82.93%, respectively. The AUC for IL-6 combined with EB virus in a replicative state was 0.900 ( P <0.000 1), with negative and positive predictive value of 84.09% and 73.33%, respectively. In summary, the imbalance of proinflammatory and anti-inflammatory cytokines varies between drugs, with EBV in a replication-activated state, combined with elevated levels of IL-2 as well as IL-6 expression being a risk factor for relapse in patients treated with anti-TNF-α-related drugs and VDZ.

Chronic hepatitis B (CHB) infection is influenced by both virological and host factors. A total of 5,920 CHB patients were classified into four groups based on HBV seromarkers: three-generation families (CHB grandmother, mother, and child), two-generation families (CHB mother/child pairs), individuals recovered from HBV infection, and a control group. Serological markers, viral load, liver function tests (LFT), HBV mutations, HLA-DQ variations, cytokine polymorphisms, and liver stiffness measurements (LSM) were analyzed using FibroScan. Point mutations in genes such as core/pre-core (G1896A/G1899A), polymerase (H248N, H267Q, N263D), S (G145R, S143L), and X (C1500T, T1464C) were observed in 30% of three-generation pairs and 20% of two-generation pairs. The three-generation group exhibited the highest mean liver stiffness measurement (LSM) (4.94 ± 1.24 kPa), which is considered a predictor for the development of hepatocellular carcinoma (HCC). Subsequent HLA allele analysis identified HLA-DQB105:01 (OR = 0.27) as a risk factor for treatment resistance, while HLA-DQB105 (OR = 0.98), HLA-DQB103 (OR = 0.80), and HLA-DQB104:01 (OR = 0.70) were associated with HBV persistence in both three- and two-generation groups. Higher frequencies of specific polymorphisms, including G/G (TNF-α: 75%; IL-18: 74%), A/A (IL-10: 74.28%), and C/C (IL-1ß: 80%), were significantly linked to persistent infection. Analysis of viral sequences, HLA-DQB1 variations, cytokine polymorphisms, and genetic relationships within the phylogenetic tree revealed that 40% of CHB patients from three-generation families were infected by a shared source of transmission, as indicated by the presence of the same HBV genotype. This study underscores the complex interplay of host and viral factors that influence hepatitis B infection outcomes and suggests potential familial transmission pathways., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1 A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009-1.095, P = 0.02) and oncostatin-M (OSM) levels ( [OR] = 1.041, [95% CI] = 1.001-1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884-0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929-0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922-0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS., (© 2024. The Author(s).)

Clinical samples are routinely inactivated before molecular assays to prevent pathogen transmission. Antibody-based assays are sensitive to changes in analyte conformation, but the impact of inactivation on the analyte detectability has been overlooked. This study assessed the effects of commonly used inactivation-methods, Triton X-100 (0.5%) and heat (60 °C, 1 h), on cytokine/chemokine detection in plasma, lung aspirates, and nasopharyngeal samples. Heat significantly reduced analyte detectability in plasma (IL-12p40, IL-15, IL-16, VEGF, IL-7, TNF-β) by 33-99% (p ≤ 0.02), while Triton X-100 minimally affected analytes in plasma and nasopharyngeal samples (11-37%, p ≤ 0.04) and had no significant impact on lung aspirates. Structural analysis revealed that cytokines affected by heat had more hydrophobic residues and higher instability-indices. As the protein-detectability was affected differently in different sample types, the sample environment could also influence protein stability. This underscores the importance of selecting the most suitable inactivation methods for clinical samples to ensure accurate cytokine/chemokine analysis in both clinical and research settings., (© 2024. Crown.)

Background: Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS)., Methods: Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-𝜿B pathway related protein, and vascular density markers were determined., Results: There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-𝜿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats., Conclusions: Together, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS., (© 2024. The Author(s).)

Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured concentrations of circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and COVID-19 patients, some of whom had unfortunately died by the end of the study enrollment, and performed a correlation analysis between plasma variables and bacterial abundances. Rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitzii and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi . Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity and providing potential therapeutic targets for managing COVID-19.IMPORTANCEOutcomes in coronavirus disease 2019 (COVID-19) are highly disparate and are associated with uncontrolled inflammation; however, the individual factors that lead to this uncontrolled inflammation are not fully understood. Here, we report that severe COVID-19 is associated with systemic inflammation, microbial translocation, and microbial dysbiosis. The rectal and oropharyngeal microbiomes of COVID-19 patients were characterized by a decreased abundance of commensal bacteria and an increased abundance of opportunistic pathogens, which positively correlated with markers of inflammation and microbial translocation. These microbial perturbations may, therefore, contribute to disease severity in COVID-19 and highlight the potential for microbiome-based interventions in improving COVID-19 outcomes., Competing Interests: The authors declare no conflict of interest.

Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats. The arthritis model was established through intradermal injection of CFA (100 μL) in the sub-plantar region of the right hind paw. The arthritic animals were treated orally with NCF at 5 and 10 mg/kg and indomethacin (Indo) at 5 mg/kg body weight as reference control. NCF treatment remarkably alleviated inflammatory joint swelling and arthritic index. The radiological and histological analysis revealed evidence of the beneficial effects of NCF. NCF treatment decreased the content of pro-inflammatory cytokines (TNF-α and IL-1β) and myeloperoxidase (MPO) activity and restored the anti-inflammatory cytokine (IL-10) in the paw joints. The serum levels of pro-inflammatory cytokines were also markedly reduced in the NCF (10 mg/kg) treatment group. Moreover, the arthritis-induced inflammatory mediators, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the toll-like receptor (TLR)-4, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling proteins were substantially decreased in the NCF treatment groups. NCF treatment also restored the antioxidant defense enzymes and abrogated lipid peroxidation in the paw tissue. Our findings strongly suggest that NCF is a promising therapeutic molecule for rheumatoid arthritis, inspiring further research, and development in this area., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infection is one of the leading causes of death in patients with hematologic cancers. Hematologic cancer patients with compromised immune systems are already susceptible to infections, which come on even more rapidly and are difficult to control after they develop neutrophil deficiencies from high-dose chemotherapy. After patients have developed an infection, the determination of the type of infection becomes a priority for clinicians. In this review, we summarize the biomarkers currently used for the prediction of infections in patients with hematologic cancers; procalcitonin, CD64, cytokines, and CD14 et al. can be used to determine bacterial infections, and (1-3)-β-D-glucan and galactomannan et al. can be used as a determination of fungal infections. We have also focused on the use of metagenomic next-generation sequencing in infections in patients with hematologic cancers, which has excellent clinical value in infection prediction and can detect microorganisms that cannot be detected by conventional testing methods such as blood cultures. Of course, we also focused on infection biomarkers that are not yet used in blood cancer patients but could be used as a future research direction, e.g., human neutrophil lipocalin, serum amyloid A, and heparin-binding protein et al. Finally, clinicians need to combine multiple infection biomarkers, the patient's clinical condition, local susceptibility to the type of infection, and many other factors to make a determination of the type of infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen and Ma.)

Introduction: Bacteremia is a life-threatening condition that can progress to sepsis and septic shock, leading to significant mortality in the emergency department (ED). The standard diagnostic method, blood culture, is time-consuming and prone to false positives and false negatives. Although not widely accepted, several clinical and artificial intelligence-based algorithms have been recently developed to predict bacteremia. However, these strategies require further identification of new variables to improve their diagnostic accuracy. This study proposes a novel strategy to predict positive blood cultures by assessing sepsis-induced immunosuppression status through endotoxin tolerance assessment., Methods: Optimal assay conditions have been explored and tested in sepsis-suspected patients meeting the Sepsis-3 criteria. Blood samples were collected at ED admission, and endotoxin (lipopolysaccharide, LPS) challenge was performed to evaluate the innate immune response through cytokine profiling., Results: Clinical variables, immune cell population biomarkers, and cytokine levels (tumor necrosis factor [TNFα], IL-1β, IL-6, IL-8, and IL-10) were measured. Patients with positive blood cultures exhibited significantly lower TNFα production after LPS challenge than did those with negative blood cultures. The study also included a validation cohort to confirm that the response was consistent., Discussion: The results of this study highlight the innate immune system immunosuppression state as a critical parameter for sepsis diagnosis. Notably, the present study identified a reduction in monocyte populations and specific cytokine profiles as potential predictive markers. This study showed that the LPS challenge can be used to effectively distinguish between patients with bloodstream infection leading to sepsis and those whose blood cultures are negative, providinga rapid and reliable diagnostic tool to predict positive blood cultures. The potential applicability of these findings could enhance clinical practice in terms of the accuracy and promptness of sepsis diagnosis in the ED, improving patient outcomes through timely and appropriate treatment., Competing Interests: EH-J, AU, XP, and JS are employees/advisors of the spin-off company Loop Diagnostics related to this biomarker. EH-J, EP-M, XP and JS are shareholders of a spin-off company Loop Diagnostics related to this biomarker. AL and EM have received honoraria from Loop Diagnostics. JS and EH-J are the authors of a PCT patent application to protect against the use of the method and kit for the early detection of sepsis WO2021245025A1. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hernández-Jiménez, Plata-Menchaca, Berbel, López de Egea, Dastis-Arias, García-Tejada, Sbraga, Malchair, García Muñoz, Larrad Blasco, Molina Ramírez, Pérez Fernández, Sabater Riera and Ulsamer.)

Cystic ovarian disease (COD) with uterine abnormalities is a postpartum reproductive pathology in Egyptian buffaloes causing significant economic losses. In this study, we aimed to employ various diagnostic methods for detecting cystic ovarian disease (COD) in Egyptian buffaloes. tour study assessed the effectiveness of the GnRH/PGF2α protocol as a treatment strategy. Our goal was to determine if this protocol could effectively reduce economic losses associated with cystic ovarian disease and improve herd fertility in Egyptian buffaloes. Eighty Egyptian buffalo cows were included in this study. They were identified to have follicular cysts through rectal examination, which was confirmed by ultrasonography. These buffaloes were then divided into two main groups: the COD Control (untreated) (GA) (n = 40) and COD group (GB) (n = 40) treated with GnRH/PGF2α. According to our immunological studies, buffaloes in the COD-treated group (GB) exhibited significantly lower serum levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) compared to the control group. This observation was consistent with the decline in E2 levels and the increase in P4 levels (p < 0.01-0.001) observed in the treated animals compared to the untreated group. Furthermore, serum cortisol and glucose concentrations decreased in COD-treated buffaloes. Histopathological examination of ovaries and uterine tissue from slaughtered COD buffaloes has revealed significant structural alterations. These include the presence of ovarian cysts of varying sizes with vacuolar degeneration. Additionally, lymphoplasmacytic endometritis was observed in the uterine tissue of affected animals, featuring degeneration and desquamation of the endometrial lining accompanied by infiltration of mononuclear inflammatory cells. Severe and prolonged cases of COD, which did not respond to treatment, exhibited marked adverse pathological changes upon histopathological assessment of the genital tract. In conclusion, hormonal treatment with GnRH/PGF2α appears to be effective in treating COD-affected animals. The study provides valuable insights into the immunological, biochemical, and histopathological aspects of cystic ovaries associated with uterine disorders in Egyptian buffaloes, while also evaluating hormonal treatment for cystic ovarian disease as a means to minimize economic losses and improve herd fertility in this species., (© 2024. The Author(s).)

Background: Surgery induces a temporal change in the immune system, which might be modified by regional anesthesia. Applying a bilateral preoperative anterior quadratus lumborum block has proven to be a safe and effective technique in pain management after abdominal and retroperitoneal surgery, but the effect on the immune response is not thoroughly investigated., Methods: This study is a substudy of a randomized, controlled, double-blinded trial of patients undergoing laparoscopic hemicolectomy due to colon cancer. Twenty-two patients were randomized to undergo either a bilateral anterior quadratus lumborum nerve block with a total of 60 mL ropivacaine 0.375% or placebo with corresponding isotonic saline injections. The main objective of this exploratory substudy was to investigate the systemic immune response in the first postoperative day by examining changes in blood transcript levels (n=750) and stimulated secretion of cytokines (n=17) on ex vivo activation with microbial ligands and anti-CD3/CD28., Results: Using unsupervised data analysis tools, we observed no effect of the bilateral anterior quadratus lumborum nerve block on gene expression in immune cells (permutational multivariate analysis of variance using distance matrices: F=0.52, p=0.96), abundances of major immune cell populations (Wilcoxon rank-sum test: p>0.05), and stimulated cytokine secretion (Wilcoxon rank-sum test: p>0.05)., Conclusions: Our study provides evidence that administration of bilateral anterior quadratus lumborum nerve block as a part of a multimodal analgesic regimen in an enhanced recovery after surgery for laparoscopic hemicolectomy in this cohort does not alter the systemic immune response. Trial registration number NCT03570541., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Constipation is a functional disorder of the gastrointestinal system characterized by difficult bowel movements, infrequent defecation, reduced water content, and hard stools. This study aims to evaluate the preventive effects of fermented gold kiwis (FGK) on loperamide-induced constipation in rats and investigate its efficacy in improving constipation symptoms in human patients through a randomized clinical trial. In the animal study, FGK was administered orally at doses of 50, 125, and 250 mg/kg to constipated rats for two weeks, resulting in significant improvements in constipation parameters. FGK increased serum serotonin and acetylcholine levels and suppressed increases in serum dopamine concentration. FGK also upregulated mRNA expression of the serotonin-synthesizing receptors 5-HT3R and 5-HT4R and suppressed the expression of the dopamine 2-receptor (D2R) in the duodenum. Furthermore, FGK inhibited inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In the clinical trials, the improvement in constipation symptoms was evaluated using the gastrointestinal symptom rating scale (GSRS). Clinical trial participants reported significant improvements in constipation symptoms after receiving FGK. These findings suggest that FGK effectively relieves constipation in both animals and humans, indicating its potential as an effective dietary supplement.

Background: Numerous studies have established that probiotics or prebiotics can relieve the symptoms of allergic rhinitis (AR), but their mechanism of action remain underexplored. This study aimed to observe the clinical efficacy of probiotics combined with prebiotics in seasonal AR patients and explore their underlying mechanisms., Methods: We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. The test group was given probiotics combined with prebiotics, whereas the placebo group was administered simulated preparation for 90 days. Outcome measures included total nasal symptom score (TNSS), visual analog scale, rhinitis quality of life questionnaire, fractional exhaled nitric oxide, and the rate and intensity of Loratadine use. Serum TNF-α, INF-γ, IL-4, IL-17, and IgE levels were measured by enzyme-linked immunosorbent assay. Intestinal microbiota was detected by 16S rRNA gene sequencing and quantitative PCR. Short-chain fatty acids were analyzed by gas chromatography-mass spectrometry., Results: 106 participants (N = 53 for both test group and placebo group) completed the study. From baseline to day 91, mean difference between groups (MDBG) in the reduction of TNSS was -1.1 (-2.2, -0.1) (P = 0.04); MDBG in the increment of TNF-α was 7.1 pg/ml (95% CI: 0.8, 13.4, P = 0.03); the INF-γ level was significantly increased (P = 0.01), whereas that of IL-17 (P = 0.005) was significantly decreased in the test group, whilst mean difference within groups was not statistically significant in the placebo group; MDBG in the increment of acetate was 12.4% (95% CI: 7.1%, 17.6%, P <0.001). After the administration of probiotics and prebiotics, the composition and metabolic function of the intestinal microbiota were significantly altered and positively related to the beneficial effect on seasonal AR patients., Conclusion: Probiotics combined with prebiotics administered for 90 days significantly attenuated the symptoms of seasonal AR patients, which may related to fluctuations in the composition and metabolic function of the intestinal microbiota and further ameliorating host immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from National Natural Science Foundation of China (82070035, 82370043) and Yongzetai Biotechnology (Beijing) Co. The funder had the following involvement in the study: drug supply, and collection of data., (Copyright © 2024 Hou, Wang, Zhou, Huo, Chen, Li, Ding, Li, Zhao, He, Da, Ma, Qiang, Chen, Bai, Cui, Gao and Liu.)

Aim: This study aimed to evaluate the predictive value of serum humoral factors in determining the therapeutic responses to biologic DMARDs (bDMARDs), especially TNF inhibitors (TNFis), in patients with RA., Methods: A cohort of 52 patients with RA who were treated with bDMARDs, including TNFis, abatacept, and tocilizumab, was analyzed. Serum samples were collected at baseline (t1), 5 ± 1 (t2), and 14 ± 2 weeks (t3) after treatment. A bead-based immunoassay was used to quantify serum cytokines/chemokines. Treatment response was determined 1 year after initiation., Results: Distinct patterns of IL-6 behaviors were observed among different bDMARDs. Patients exhibiting IL-6 rebound at 14 weeks were more likely to be non-responders to TNFi after 1 year, and this rebound appeared to be associated with increases in IFN-γ and IL-12 levels. IFN-β was more detectable than IFN-α2 in RA. Additionally, patients with measurable IFN-β at baseline tended to be TNFi responders., Conclusion: Monitoring serum humoral factors may offer valuable insights into the likelihood of therapeutic success of TNFi in patients with RA. IL-6 rebound at 14 weeks might serve as an early indicator of non-responsiveness to TNFi. These findings highlight the potential of personalized treatment strategies for RA based on serum humoral factor profiling. Larger prospective studies are needed to validate these results and elucidate the underlying mechanisms., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: The gut-brain axis may mediate mood changes due to strenuous exercise. Therefore, probiotic supplementation may mitigate mood worsening., Purpose: The present study aims to evaluate the effect of probiotic supplementation on mood and immunometabolic parameters after a marathon., Materials and Methods: Fourteen marathon runners were selected and divided into placebo and probiotic groups that were supplemented for 30 days. Before and after the marathon, mood (POMS) was assessed, and blood was collected for analysis of immunometabolic parameters. Statistical analysis was performed, and p < 0.05 was considered to determine statistically differences., Results: Tension decreased after the marathon in both groups. Vigor decreased only in the placebo group. Fatigue increased after the marathon in both groups. TMD increased after the marathon in placebo. The IL2/IL-4 ratio decreased in the probiotic group after the marathon compared to before and increased compared to the placebo group. The IL-10 increased after the marathon in placebo. TNF-α increased after the marathon in probiotics. The TNF-α/IL-10 ratio decreased after the marathon in both groups. LPS decreased in the probiotic group after the marathon compared to before and in the placebo group., Conclusions: Thirty days of probiotic supplementation attenuated the impact of marathons on mood worsening. The decrease in LPS in the probiotic group mediated the change in the pro/anti-inflammatory balance, indicating an immunometabolic mechanism by which the gut-brain axis impacts mood after strenuous exercise.

Objective: To define the impact of obesity on inflammatory and oxidative disturbances in antipsychotic-treated schizophrenia patients., Methods: Several cytokines, inflammatory, metabolic, and oxidative status markers were evaluated in obese (n = 40) and non-obese (n = 40) antipsychotic-treated patients and compared with age-and BMI-matched controls (n = 80)., Results: Schizophrenia patients had higher leptin, TNF-α, adiponectin, visfatin, resistin, P-selectin, NPY, BDNF, CD40-L, MCP-1, and malondialdehyde, and lower IL-6, ghrelin, neopterin, and vitamin E levels compared to their respective controls (p < 0.001). Total oxidant status was higher in non-obese patients compared to controls (p < 0.001), total antioxidant capacity was higher in obese compared to non-obese patients (p < 0.01), but vitamin A and paraoxonase levels were not different. High sensitive-CRP levels were higher in obsese controls relative to non-obese controls (p < 0.05) and in obese patients relative to non-obese patients (p < 0.001). Fasting glucose, insulin, HbA1c, HOMA-IR, uric acid, total cholesterol, and triglyceride concentrations were higher in obese patients compared to non-obese patients. Insulin concentrations and HOMA-IR were also higher in obese controls than in non-obese controls., Conclusions: Our results suggest that inflammatory responses and oxidative stress develop independently from obesity in antipsychotic-treated schizophrenia patients. However, schizophrenia-induced obesity causes metabolic disturbances; thereby, obese schizophrenia patients are more liable to cardiovascular events and progress of metabolic syndrome than non-obese patients., (© 2024 John Wiley & Sons Ltd.)

Objective: To explore the predictive value of cellular inflammatory factors and T cell subsets for disease recurrence and prognosis in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD)., Methods: Serum samples were collected from the two groups to detect and compare the levels of inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], T cell subsets (CD4+, CD8+), and clinical related indicators. Pearson correlation analysis was used to analyze the correlation between inflammatory cytokines, T cell subsets, and clinical indicators. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of serum inflammatory factors and T cell subsets for acute exacerbations of COPD., Results: The observation group had higher levels of IL-1β, IL-6, TNF-α, and CD8+, and lower CD4+ levels (P<0.05). The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) was lower, while procalcitonin (PCT) and white blood cell count (WBC) were higher (P<0.05). Correlation analysis showed positive correlations between IL-1β, IL-6, TNF-α, and CD8+, and negative correlations with CD4+ and FEV1/FVC (P<0.05). After 6 months, 15 out of 73 patients had acute recurrences, with higher IL-1β, IL-6, TNF-α, and CD8+ levels (P<0.05). Binary logistic regression identified IL-1β, IL-6, TNF-α, and CD8+ as significant predictors of exacerbations, while CD4+ was protective. ROC analysis showed that combined biomarkers had the highest predictive efficiency (AUC = 0.907)., Conclusion: This study is the first to integrate multiple serum inflammatory factors and T cell subsets into a comprehensive predictive model for acute recurrence of COPD within six months (AUC = 0.907), offering a more accurate prediction than traditional methods. The findings underscore the value of these biomarkers in clinical follow-up and highlight their independent predictive power, providing new insights into the interaction between immune markers and clinical indicators in COPD exacerbations., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Deng et al.)

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and the risk of colorectal cancer, but the findings have been inconsistent. In this study, we employed a 2-sample Mendelian randomization (MR) analysis, primarily using the inverse variance weighted approach, to investigate the causal relationship between inflammatory cytokines and CRC. The forward MR analysis revealed a positive association between higher levels of interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor (OR: 1.44, P = .001), and MIG (OR: 1.23, P = .040) with an increased risk of rectal cancer. Conversely, higher levels of macrophage colony-stimulating factor (OR: 0.80, P = .010) may potentially decrease the risk of colon cancer. In the reverse MR analysis, it was found that rectal cancer is linked to higher levels of IL-1b (OR: 0.93, P = .022), IL-1ra (OR: 0.90, P = .001), IL-5 (OR: 0.93, P = .022), IL-9 (OR: 0.93, P = .017), and TNF-a (OR: 0.91, P = .003). Additionally, colon cancer is associated with elevated levels of FGF-Basic (OR: 1.10, P = .028). Consistent results were also found in MR-Egger, weighted median, and weighted mode analysis. Our study presents novel evidence supporting the causal relationship between inflammatory cytokines and CRC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The immune system and inflammatory processes play crucial roles in the development of esophageal cancer (EC). This study aimed to investigate the causal relationships between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and EC, with a particular focus on the mediating role of circulating inflammatory proteins. Utilizing public genetic data, we applied a 2-sample Mendelian Randomization (MR) method to examine the causal relationships between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and EC. Comprehensive sensitivity analyses were conducted to assess the robustness, heterogeneity, and horizontal pleiotropy of the MR results. Additionally, a 2-step MR method was employed to quantify the impact and proportion of immune cell phenotypes mediated by circulating inflammatory proteins on EC. Eleven immune cell phenotypes and 1 inflammatory cytokine were found to have causal relationships with EC, with results stable across all sensitivity analyses. Mediation analyses revealed that only 2 cell phenotypes had causal relationships with EC through interleukin-10: CD3 on human leukocyte antigen-DR (HLA-DR)+ T cells (mediation effect = -0.009; mediation proportion = 12.01%) and monocytic myeloid-derived suppressor cell absolute count (mediation effect = 0.018; mediation proportion = 18.97%). This study enhances the understanding of the causal relationships between immune cells, circulating inflammatory proteins, and EC. The findings highlight the potential mediating role of interleukin-10, providing new insights into the mechanisms by which immune cells may influence esophageal tumorigenesis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood., Methods: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP)., Results: Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression., Conclusions: Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression., (© 2024. The Author(s).)

Introduction: Autism Spectrum Disorder (ASD) is a disorder that severely affects neurodevelopment, and its underlying causes are not yet entirely understood. Research suggests that there may be a connection between the occurrence of ASD and changes in immune responses. This study aims to know if some biochemical and inflammatory cytokines are promising biomarkers for ASD and whether they are involved in the pathogenesis of ASD., Methods: The serum levels of CRP, TNF-α, TGF-β, IL-1β, IL-10, 1 L-8, and IL-6 were measured in all of the patients (n = 22) and in the healthy (n = 12) children using ELISA method., Results: The serum concentrations of IL-10 and IL-8 were significantly lower in the ASD patients compared to the control group (p < 0.05) and there were not significant differences between CRP, TNF-α, TGF-β, IL-6 and IL-1β levels in two groups. There were positive correlations between CRP and IL-10, also CRP and IL-8, in ASD group. In contrast to the ASD patients, the correlations of IL-8, IL-10, and CRP were not significant in the control group., Conclusion: In conclusion, this study highlights the potential role of certain biochemical markers and inflammatory cytokines in ASD. Specifically, the lower levels of IL-10 and IL-8 in ASD patients, along with the significant correlations between CRP and these cytokines, suggest an altered immune response in individuals with ASD. These findings support the hypothesis that immune dysregulation may be involved in ASD pathogenesis. Further research is needed to explore these biomarkers and their mechanistic links to ASD, which could lead to improved diagnostics or therapeutic strategies., (© 2024. The Author(s).)

The implication of Torquetenovirus (TTV) in ischemic heart disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, pro-inflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects and 86 individuals with IHD (aged 55-75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with non-IHD (aged 65-96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension, and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4 log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia <4 log. No significant difference in cytokine production was observed between IHD patients and non-IHD with TTV viremia ≥4 log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4 log displayed higher NLR and SIRI index than those with TTV viremia <4 log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented pro-inflammatory response and immunosenescence., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Globally, schizophrenia is one of the main causes of disability. Approximately 1 % of the general population suffers from schizophrenia, and 30 % of cases are unresponsive to therapy. Clozapine is the gold standard for therapy-resistant schizophrenia (TRS), yet it has limited effectiveness and serious adverse events in some patients. Because of the possibility of severe neutropenia, clozapine administration requires monthly hematological monitoring in the first four months. Previous investigations have demonstrated the immune system alteration after clozapine treatment in schizophrenia patients. Besides, it has been proposed that clozapine changes the cytokines profile in schizophrenia patients. These findings highlighted the need to learn more about the disease's etiology and investigate the relationship between peripheral immune system markers and clozapine response to support strategies for better treatment outcomes. The time decision-making to start clozapine could be significantly decreased if some biomarkers were developed to assist physicians in anticipating whether a particular patient will respond to the medication. Therefore, this study aimed to comprehensively review the effect of clozapine on immune-related biomarkers in schizophrenia patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively investigate levels of circulating cytokines, changes in frequencies of various immune cell subsets and expression of proliferation and checkpoint molecules on T cells in the peripheral blood after yttrium-90 radioembolization (TARE) of colorectal cancer liver metastases (CLM)., Materials and Methods: We prospectively collected, isolated, and froze peripheral blood mononuclear cells (PBMC) and plasma samples from 15 patients immediately before, immediately after, 3 and 6 weeks post-TARE of CLM. Plasma samples were assessed for various cytokines using a multiplex immunoassay platform. PBMC samples were analyzed in a monocyte/dendritic cell (DC)/B cell flow panel and a T cell activation/exhaustion flow phenotyping panel. We compared the levels at the respective time points using Wilcoxon signed rank test., Results: IFN-g significantly decreased immediately after (mean 1.62 vs. 3.02 at baseline, p = 0.04) and increased at 6 weeks compared to the immediately post-TARE nadir (mean 9.42 vs. 1.62, p = 0.04). IL-10 decreased at 3 weeks (mean 0.36 vs. 1.75, p = 0.025) post-TARE compared to baseline. Increased CD3 + T cells (mean 78.24 vs. 60.8, p = 0.002) and decreased CTLA-4 + CD4 + T cells (mean 2.58 vs. 4.41, p = 0.033) were observed at 3 weeks compared to baseline. Increased Ki-67 + proliferating CD8 + T cells at 3 and 6 weeks (mean 7.28 and 9.06, respectively, vs. 3.93 at baseline, p = 0.02 and 0.03) were recorded., Conclusion: A shift toward a favorable antitumoral cytokinic and immune cells response was observed after TARE. Significant changes were in specialized immune cells subsets playing important roles in the activation of the immune system. These results support trials combining TARE with immunotherapy for patients with CLM., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Objectives: The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection., Methods: We enrolled 628 consecutive children aged ≤15 years, admitted for TB suspicion. Multiple cytokine levels in QuantiFERON Gold In-Tube supernatants and antigen 85B (Ag85B) antibodies were assessed in children who tested positive with either Xpert TB or mycobacterial culture. The results were compared with those of control children., Results: Among the biomarkers most strongly associated with TB, random forest classification analysis selected Ag85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system. The receiver operating characteristic curve derived from our scoring system showed an area under the curve of 0.95 (0.91-0.99), yielding 91% sensitivity and 88% specificity. The internal bootstrap validation gave the following 95% confidence intervals for the score performance: sensitivity 71%-97% and specificity 79%-99%., Conclusions: This study suggests that supplementing the QuantiFERON assay with a combination of serological and T-cell markers could enhance childhood TB screening regardless of HIV status and age. Further validation among the target population is necessary to confirm the performance of this scoring system., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the relationship between 35 trace metals in scalp hair and the glioma risk as well as the potential mediating roles of 27 plasma inflammatory cytokines., Methods: A case-control study involving 228 participants was performed in southeastern China. Trace metals in scalp hair were analyzed using inductively coupled plasma mass spectrometry, and multiplex cytokines were detected based on Luminex® technology. The least absolute shrinkage and selection operator (LASSO) regression in combination with four machine learning methods were used to select trace metals associated with gliomas. The joint exposure effect of trace metals was estimated using the generalized weighted quantile sum (gWQS) regression and quantile-based g-computation (qgcomp) algorithms., Results: Both LASSO regression and random forest algorithms identified five trace metals (gadolinium [Gd], lithium [Li], thulium [Tm], thorium [Th], and molybdenum [Mo]) associated with gliomas. After adjustments for potential confounders, Gd (odds ratio [OR] = 2.84, 95% confidence interval [CI]: 1.89-4.43) and Li (OR = 1.77, 95% CI: 1.04-3.02) concentrations were positively associated with glioma risk, while Tm (OR = 0.36, 95% CI: 0.17-0.73) and Th (OR = 0.45, 95% CI: 0.28-0.71) exhibited inverse associations. Both gWQS and qgcomp algorithms showed Gd contributed most to the mixture effect. Moreover, there was a significant interaction between Gd and Tm or Th on glioma risk (p < 0.05). Notably, granulocyte-macrophage colony-stimulating factor (GM-CSF) mediated the association between Gd exposure and glioma risk by 25.75%., Interpretation: These findings suggest potential associations of certain trace metals, especially for Gd, with glioma risk, and may provide new insights into the mechanisms underlying from an inflammatory response perspective., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice., Methods: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated., Results: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates., Conclusion: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4 + and total CD8 + T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4 + CD69 + and CD8 + CD69 + T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Endotoxemia is a systemic inflammatory condition caused by lipopolysaccharide (LPS) stimulation, which produces inflammatory cytokines. Fuzapladib (FZP) inhibits the activation of adhesion molecules found on the surface of inflammatory cells, mitigating inflammation. In this study, we evaluated the therapeutic effects of fuzapladib on inflammatory cytokines and cardio-respiratory function using an LPS-induced endotoxemic porcine model. Fifteen pigs were separated into three groups: low-FZP (n=5), high-FZP (n=5), and control (n=5). Pigs were administered LPS under general anesthesia, and complete blood cell count, blood biochemistry, inflammatory cytokines, and cardio-respiratory function were evaluated. Statistical analysis was performed using a linear mixed-effects model and the Steel-Dwass test, with a significance threshold of P<0.05. During the 4 hr experimental period, one pig in the control group and two pigs in the low-FZP group died due to hypoxemia and hypotension. In the early acute changes following LPS administration, the high-FZP group maintained significantly higher arterial oxygen partial pressure and normal blood pressure compared to the control group. Although interleukin-6 levels increased in all groups during the experiment, they were significantly lower in the high-FZP group compared to the control group. Other parameters showed no clinically significant differences. In conclusion, while high-dose fuzapladib did not reduce organ damage in the porcine endotoxemia model, it suppressed interleukin-6 production, delayed the progression of deterioration, and contributed to a reduction in mortality during the observation period.

There is a growing body of evidence suggesting that dietary polysaccharides play a crucial role in preventing metabolic syndrome (MetS) through their interaction with gut microbes. Tea (Camellia sinensis L.) flower polysacchride (TFPS) is a novel functional compound known for its diverse beneficial effects in both vivo and vitro. To further investigate the effects of TFPS on MetS and gut microbiota, and the possible association between gut microbiota and their activities, this study was carried out on mice that were fed a high-fat diet (HFD) and given oral TFPS at a dose of 400 and 800 mg/kg·body weight (BW)/d, respectively. TFPS treatment significantly mitigated HFD-induced MetS, evidenced by reductions in body weight, fat accumulation, plasma levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-1β, along with an increase in plasma IL-10 levels. Furthermore, TFPS induced alterations in the diversity and composition of HFD-induced gut microbiota. Specifically, TFPS influenced the relative abundance of 11 genera, including Lactobacillus and Lactococcus, which showed strong correlations with metabolic improvements and likely contributed to the amelioration of MetS. In conclusion, TFPS exhibits promising prebiotic properties in preventing MetS and regulating gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Type 2 diabetes mellitus (T2DM) represents approximately 90 % of all DM cases and is primarily caused by an imbalance in blood glucose homeostasis due to inadequate insulin secretion or insulin resistance. This study explores the potential therapeutic effects of chitosan guanidine (CSG) on a T2DM mouse model. The findings reveal that CSG significantly enhances oral glucose tolerance (OGTT) and insulin sensitivity (ITT), reduces fasting blood glucose (FBG) levels, and suppresses the expression of proinflammatory cytokines in T2DM mice. These changes improve insulin resistance and diminish inflammation. Additionally, CSG markedly ameliorates lipid metabolism disorders, lowers total cholesterol (TC) and triglyceride (TG) levels, and inhibits hepatic fat accumulation. 16S rRNA and Spearman correlation analyses indicate that CSG promotes the relative abundance of probiotic genera such as Bacteroidota, Patescibacteria, Actinobacteria, and Cyanobacteria. These bacteria are positively correlated with short-chain fatty acids (SCFAs) and high-density lipoprotein cholesterol (HDLC) levels. Conversely, CSG reduces the relative abundance of pathogenic bacteria, including Proteobacteria and Ralstonia, leading to an improved intestinal microbial community composition in T2DM mice and alleviating T2DM symptoms. These results suggest that CSG holds significant potential as a non-insulin therapeutic agent for diabetes management., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled. We confirm that the mentioned received grants in the “Acknowledgement” section, did not lead to any conflicts of interest regarding the publication of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)