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Background: The COVID-19 (SARS-CoV-2) epidemic has posed a major challenge to global public health, especially in children. Some children may experience secondary infection with Mycoplasma pneumoniae after SARS-CoV-2 infection, which has attracted widespread attention. Studies have shown that eosinophils play an important role in respiratory tract infections and are involved in regulating immune responses and inflammatory processes. However, there is a lack of systematic research on the specific manifestations and mechanisms of eosinophils in secondary infection with Mycoplasma pneumoniae after SARS-CoV-2 infection. Objective: This study aims to explore the characteristics of immune response in children with SARS-CoV-2 infection and Mycoplasma pneumoniae infection, focusing on the changes in immune indicators such as eosinophils (EOS), immunoglobulin E (IgE), interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). Methods: This study is a retrospective observational study, and a total of pediatric patients who were treated in our hospital from January 2023 to December 2023 were included. The study group included children who were diagnosed with SARS-CoV-2 infection and further infected with Mycoplasma pneumoniae, and the control group included children who were only infected with SARS-CoV-2 and had no other pathogens. The clinical data of the two groups of patients, including absolute eosinophil value, IgE quantification, IL-6, CRP and PCT levels, were collected and analyzed, and statistical comparisons were performed. Results: A total of 134 children were included, including 79 in the study group and 55 in the control group. The absolute eosinophil value [0.17 (0.09, 0.31) vs. 0.09 (0.06, 0.23), P < 0.01] and IgE level [59.28 (37.54, 256.88) vs. 22.00 (11.00, 113.10) P < 0.01] of the children in the study group were significantly higher than those in the control group, while IL-6 [16.81(4.72,31.86) vs. 9.5(3,57.3), P = 0.602], CRP [2.82(1.10,6.13) vs. 1.94(0.50,8.94), P = 0.528] and PCT[0.12(0.08,0.20) vs. 0.12(0.10,0.24), P = 0.329] were no significant difference between the two groups. Binary logistic regression analysis showed that the absolute value of eosinophils and IgE were independent risk factors for secondary infection of Mycoplasma pneumoniae after SARS-CoV-2 infection. Conclusion: This study shows that after SARS-CoV-2 infection, the increase in eosinophils and the increase in related immune indicators IgE may be closely related to secondary infection with Mycoplasma pneumoniae. This study provides an important basis for understanding the immune response of children after SARS-CoV-2 infection and its related clinical management, suggesting that clinicians should closely monitor the eosinophil count and IgE level of children after SARS-CoV-2 infection, especially for children at risk of secondary infection, so as to take timely intervention measures to prevent secondary infection with Mycoplasma pneumoniae and improve the prognosis of children. [ABSTRACT FROM AUTHOR]

Background: To investigate the effects of implementing group progressive resistance training on Maximal Oxygen consumption (VC>2max), Maximum Ventilation per minute (VEmax), Maximal Oxygen pulse (O2pulsemax), Maximum Heart Rate (HRmax), and Modified Medical Research Council dyspnea scale (mMRC) in elderly patients with chronic obstructive pulmonary disease. Methods: A total number of 114 elderly patients with chronic obstructive pulmonary disease treated in the hospital from May 2022 to May 2024 were collected and divided into two groups based on different training methods. The conventional group (n=57) received routine rehabilitation training, while the organization group (n=57) received group progressive resistance training. Cardiopulmonary Exercise Testing (CPET) parameters, serum inflammatory factors, lung function indicators, and mMRC score were compared between two groups before training, 2 weeks of training, and 4 weeks of training. Results: Before training, there was no significant difference between the two groups regarding training compliance, CPET parameters, inflammatory factors, and mMRC score. After 2-4 weeks of training, both groups showed improvements in training frequency, intensity, autonomous training, and increases in VO2maX/VEmax, O2pulsemax, and HRmax. However, the organization group had higher scores in these areas and lower levels of inflammatory factors (IL-8, IL-18, IL-6, IL-12) and mMRC scores compared to the conventional group, with statistically significant differences (P<0.05). Conclusions: Group progressive resistance training can help improve the compliance of elderly patients with chronic obstructive pulmonary disease with training, reduce the body's inflammatory response, improve VO2max, VEmax, O2pulsemax, and HRmax levels, and alleviate breathing difficulties. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the inflammatory responses of fibroblast-like synoviocytes (FLS) isolated from osteoarthritis (OA) patients, stimulated with lipopolysaccharide (LPS) and interleukin-6 (IL-6). Both experimental and synthetic data were utilised to investigate the variability in IL-6 and myeloperoxidase (MPO) production and its implications for OA pathogenesis. Methods: Synovial biopsies were obtained from OA patients undergoing joint replacement surgery. FLS were isolated, cultured, and stimulated with varying concentrations of LPS and IL-6. The production of IL-6 and MPO was measured using enzyme-linked immunosorbent assays (ELISA). Synthetic data generation techniques expanded the dataset to support comprehensive statistical analyses. Results: The patterns of inflammatory responses revealed distinct patient subgroups, highlighting individual variability. The integration of synthetic data with experimental observations validated their reliability and demonstrated dose-dependent differences in IL-6 and MPO production across patients. Conclusions: The results highlighted the importance of patient-specific factors in OA inflammation and demonstrated the utility of combining experimental and synthetic data to model individual variability. The results support the development of personalised treatment strategies in OA. Future research should include larger patient datasets and an exploration of molecular mechanisms underlying these responses. [ABSTRACT FROM AUTHOR]

Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. Methods: To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Results: Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Conclusions: Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has significantly changed cancer treatment, yet predicting which patients it will benefit remains challenging. This study aimed to explore the role of two serum biomarkers, growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6), in determining the outcomes of patients receiving immunotherapy. By analyzing 85 patients with advanced cancers such as lung, kidney, and melanoma, we discovered that high levels of GDF-15 were associated with worse survival outcomes and a higher likelihood of cancer-related cachexia, a condition causing severe weight and muscle loss. Although IL-6 also showed potential as a biomarker, its impact was less pronounced. These findings suggest that GDF-15 could serve as a useful biomarker to guide treatment decisions and help identify patients who might benefit the most from immunotherapy. This research study highlights the importance of using biomarkers to optimize cancer care and improve patient outcomes. Background: Immunotherapy has transformed cancer treatment; however, predicting treatment response remains challenging. Serum biomarkers can help identify patients who are most likely to benefit from immunotherapy. Objective: This study evaluates the relationship between serum growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) levels and treatment outcomes in cancer patients undergoing second-line immunotherapy. Methods: We conducted a prospective observational study involving 85 patients with non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or malignant melanoma treated with nivolumab. The baseline serum levels of GDF-15 and IL-6 were measured by using ELISA kits. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with cachexia as a secondary outcome. Results: Elevated GDF-15 levels were significantly associated with shorter PFS (HR: 0.55, 95% CI: 0.32–0.96, p = 0.032) and OS (HR: 0.47, 95% CI: 0.25–0.90, p = 0.020). Higher IL-6 levels correlated with shorter PFS, though statistical significance was not achieved. Additionally, high GDF-15 levels were linked to increased cachexia incidence (p = 0.037). Conclusion: Our findings indicate that GDF-15 could serve as a prognostic biomarker for immunotherapy response and may also be a target for cachexia management. Further studies should explore its potential to guide clinical decision making in oncology. [ABSTRACT FROM AUTHOR]

The male reproductive impairment caused by environmental estrogens (EEs) stands as a pivotal research area in environmental toxicology. Alpha2-macroglobulin (A2M) emerges as a promising molecule capable of counteracting oxidative stress induced by EEs. This study conducted exposure experiments spanning PND1 to PND56 employing ICR mice, aiming to delve into the expression patterns of A2M and its modulated IL-6 in the testicular tissue of mice subsequent to diethylstilbestrol (DES) and benzophenone (BP) exposure, while elucidating the pivotal role of ERs in this intricate process. Our findings revealed that upon DES exposure (10 and 100 nM), there was a pronounced upregulation of A2M (mRNA and in situ protein levels) in mouse testicular tissue. Similarly, exposure to BPs (BP-1, BP-2, and BP-3, each at 10 and 1000 nM) exhibited comparable effects and increasing A2M levels in serum. Notably, BP exposure also caused an elevation in IL-6 levels (which could be directly regulated by A2M) within testicular tissue (mRNA and in situ protein). Remarkably, the specific estrogen receptor antagonist ICI 182780 (0.5 mg/kg/day) was effective in reversing the upregulation of both A2M and IL-6 induced by BP exposure. Significantly, the results of theoretical prediction of the potential ERE site in the A2m gene promoter region and ChIP-qPCR experiment provide essential and strong evidence for the key conclusion that A2m is the target gene of ER. Taken together, our study highlights EEs' ability to regulate A2M expression in the male reproductive system via the ER signaling pathway. This vital insight deepens our understanding of molecular mechanisms protecting against oxidative stress caused by EEs. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) is a tauopathic atypical parkinsonian syndrome. Recent studies suggest that inflammation may play a role in PSP pathogenesis, highlighting markers like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and cytokines such as IL-1β and IL-6. This study aimed to assess the relationship between peripheral inflammatory markers and psychological abnormalities in PSP-RS and PSP-P patients. The study included 24 participants: 12 with PSP-RS, 12 with PSP-P, and 12 controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA); however, the executive functions were evaluated using the Frontal Assessment Battery (FAB), while inflammatory markers such as IL-1β, IL6, NLR, and PLR were measured. The parameter correlation was executed using Spearman's correlation (rs). The analysis revealed significant negative correlations between NLR and MoCA (rs = −0.48), as well as between PLR and MoCA (rs = −0.60). The negative correlation between IL-1β and MoCA was statistically significant but relatively weak. This study highlights the relevance of inflammatory markers such as NLR and PLR in reflecting cognitive decline in PSP patients, with IL-1β potentially playing a protective role in cognitive function. [ABSTRACT FROM AUTHOR]

Abstract To evaluate the clinical utility of PCT, CRP, IL-6, NLR, and TyG index in improving the early diagnosis and severity assessment of acute pancreatitis (AP). This retrospective study included 137 AP patients and 30 healthy controls from Hunan Provincial People’s Hospital (January 2021–September 2023). Univariate and multivariate logistic regression analyses assessed the associations between biomarkers and severe acute pancreatitis (SAP). Receiver operating characteristic (ROC) curves, DeLong test, and Bonferroni correction were used to evaluate predictive performance. Model robustness was validated via 5-fold cross-validation. PCT, CRP, IL-6, NLR, and TyG index levels were significantly elevated in AP patients compared to controls (P 0.05). 5-fold cross-validation confirmed consistent performance (mean AUC = 0.817 ± 0.118). PCT, CRP, IL-6, NLR, and TyG index are valuable in diagnosing and assessing AP prognosis. Hyperlipidemia, CRP, and NLR are reliable independent predictors of SAP. Combining multiple biomarkers enhances diagnostic precision and provides guidance for personalized treatment strategies in AP.

Abstract Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein–Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC. Plasma EBV DNA load, IL-6 level, VEGF expressions were measured in 24 patients with NPC at presentation and various time points during and after treatment. There was a positive correlation between high plasma EBV DNA load with higher IL-6 and VEGF expression, which was closely associated with therapeutic response as well. Persistent or recurrent plasma EBV load with higher IL-6 and VEGF levels can potentially predict disease progression and may be useful to select patients for additional therapy and longer follow-up.

Interleukin-6 (IL-6) belongs to the cytokine family and plays a vital role in regulating immune response, bone maintenance, body temperature adjustment, and cell growth. The overexpression of IL-6 can indicate various health complications, such as anastomotic leakage, cancer, and chronic diseases. Therefore, the availability of highly sensitive and specific biosensing platforms for IL-6 detection is critical. In this study, for the first time, epitope-mediated IL-6-specific magnetic molecularly imprinted core–shell structures with fluorescent properties were synthesized using a three-step protocol, namely, magnetic nanoparticle functionalization, polymerization, and template removal following thorough optimization studies. The magnetic molecularly imprinted polymers (MMIPs) were characterized using dynamic and electrophoretic light scattering (DLS and ELS), revealing a hydrodynamic size of 169.9 nm and zeta potential of +17.1 mV, while Fourier transform infrared (FTIR) spectroscopy and fluorescence spectroscopy techniques showed characteristic peaks of the polymer and fluorescent tag, respectively. Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM) investigations confirmed the successful encapsulation of the magnetic core within the ca. 5-nm-thick polymeric shell. The MMIP-based electrochemical sensing platform achieved a limit of detection of 0.38 pM within a linear detection range of 0.38–380 pM, indicating high affinity (dissociation constant KD = 1.6 pM) for IL-6 protein in 50% diluted serum samples. Moreover, comparative investigations with the non-imprinted control polymer demonstrated an imprinting factor of 4, confirming high selectivity. With multifunctional features, including fluorescence, magnetic properties, and target responsiveness, the synthesized MMIPs hold significant potential for application in various sensor techniques as well as imaging. [ABSTRACT FROM AUTHOR]

Introduction: Intra‐amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra‐amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely‐used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra‐amniotic inflammation; and (2) an appropriate cut‐off value of a cervicovaginal fluid fFN concentration for the identification of intra‐amniotic inflammation. Material and Methods: This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra‐amniotic inflammation was defined as an amniotic fluid interleukin‐6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin‐6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra‐amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra‐amniotic inflammation were calculated. Results: (1) Frequency of intra‐amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra‐amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83–0.96) for the identification of intra‐amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut‐off of 125 ng/mL had a significant higher predictive performance than the traditional cut‐off (50 ng/mL) for the identification of intra‐amniotic inflammation. Conclusions: Quantitative cervicovaginal fluid fFN with a cut‐off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra‐amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra‐amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra‐amniotic inflammation. [ABSTRACT FROM AUTHOR]

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• Low-dose acetylsalicylic acid (ASA, i.e., aspirin) can mitigate the inflammatory consequences of experimental sleep restriction in healthy humans. • Low-dose ASA reduced the activity of the NF-κB pathway and COX pathway, as indicated by reduced serum CRP levels, reduced IL-6 expression and COX-1/COX-2 co-expression in LPS-stimulated monocytes in the sleep restriction condition compared to placebo. • Counter-inflammatory effects of low-dose ASA were still evident following recovery sleep, in particular in COX-1/COX-2 co-expression in LPS-stimulated monocytes. Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction. 46 healthy participants (19F/27M, age range 19–63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00–07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00–07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models. Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition). This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies. ClinicalTrials.gov NCT03377543. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. Maternal obesity during pregnancy is linked to systemic inflammation and elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6). In our previous work, we demonstrated that increased maternal IL-6 during gestation impacts intrauterine development in mice. We hypothesized that IL-6-induced inflammation alters gene expression in the developing fetus. To test this, pregnant mice were administered IL-6 or saline during mid-gestation. Newborn mouse kidneys were analyzed using mRNA-seq, miRNA-seq and whole-genome bisulfite-seq (WGBS). A multi-omics approach was employed to quantify mRNA gene expression, miRNA expression and DNA methylation, using advanced bioinformatics and data integration techniques. Our analysis identified 19 key genes present in multiple omics datasets, regulated by epigenetics and miRNAs. We constructed a regulatory network for these genes, revealing disruptions in pathways such as Mannose type O-glycan biosynthesis, the cell cycle, apoptosis and FoxO signaling. Notably, the Atp7b gene was regulated by DNA methylation and miR-223 targeting, whereas the Man2a1 gene was controlled by DNA methylation affecting energy metabolism. These findings suggest that these genes may play a role in fetal programming, potentially leading to CKD later in life due to gestational inflammation. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of intravenous Dexmedetomidine (Dex) administered perioperatively on stress response markers in patients undergoing ENT surgeries. Methods: This randomized interventional study was conducted at POFs Hospital and NUMS affiliated WMC, Wah Cantt, in collaboration with IIMC Rawalpindi, Pakistan, from October 2021 to April 2022. One hundred patients aged between 15-60 years, after satisfying the inclusion standards were randomly divided into two groups C and D. Group-C (n=50) received normal saline in addition to the standard anesthesia protocol. The intervention Group-D (n=50) was administered 1μg/kg dexmedetomidine hydrochloride intravenously over 10 minutes just before the induction followed 0.5μg/kg/hr as maintenance dose till the end of surgery. Serum inflammatory biomarkers (interleukins-6, TNF-α and cortisol) were measured in blood samples in both groups, taken at 0 (T0), 30 minutes(T1), and two hours (T2) time intervals and analyzed by using Enzyme-linked immunosorbent assay (ELISA). Data was statistically analyzed using SPSS 23. Results: The patients receiving Dex showed marked decrease in serum levels of cortisol, TNF-α and interleukins-6, from 139.73 to10.18, 99.51 to 0.96 and 85.09 to 0.96 respectively. Comparison between C and D groups revealed significant differences (p≤0.05) in these serum biomarkers. Conclusions: In the present study, intravenous Dex suppressed the intraoperative rise in levels of cytokine secretion and enhanced smooth recovery with no incidence of nausea and vomiting. These effects could be attributed to the anti-inflammatory effects of dexmedetomidine. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of a drug‐coated balloon (DCB) on inflammatory cytokines in patients with coronary artery calcification (CAC) after interventional therapy. Methods: This study included 58 patients with coronary heart disease who underwent coronary angiography (CAG) from October 2020 to September 2021. Patients were divided into CAC and non‐CAC groups, and a DCB was used to intervene in the target lesions. Ten‐milliliter preoperative and postoperative blood samples were drawn from the coronary lesions in both groups to detect the expression of serum interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and intercellular adhesion molecule‐1 (ICAM‐1). All patients were subjected to a 6‐month follow‐up to observe the incidence of major adverse cardiac events (MACEs). Results: No significant differences in baseline clinical data were found between the groups. Serum IL‐6, TNF‐α, and ICAM‐1 expressions in coronary blood samples immediately before DCB were not significantly different from those after DCB in all patients. After DCB, serum TNF‐α expression in the CAC group was significantly lower than that in the non‐CAC group (p < 0.05). In contrast, no significant difference in serum IL‐6 and ICAM‐1 expression was found between the groups. During the 6‐month follow‐up, no significant difference in the incidence of MACE was found between both groups. Conclusions: DCB reduced the expression of inflammatory cytokine TNF‐α in CAC, which may be one of the key mechanisms underlying the treatment of CAC by DCB. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein–Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC. Plasma EBV DNA load, IL-6 level, VEGF expressions were measured in 24 patients with NPC at presentation and various time points during and after treatment. There was a positive correlation between high plasma EBV DNA load with higher IL-6 and VEGF expression, which was closely associated with therapeutic response as well. Persistent or recurrent plasma EBV load with higher IL-6 and VEGF levels can potentially predict disease progression and may be useful to select patients for additional therapy and longer follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Hirschsprung’s disease (HD) is a congenital disease with incidence of 1: 10.000 births. HD is signed by part of the intestine that does not have a ganglion causing obstruction symptoms. Definitive management of HD is by performing surgery on the aganglionic bowel. Several decades ago, the management of HD required multistep surgery. However, lately one-step surgery have been developed that allow minimal intervention. The purpose of this study was to compare Interleukin-6 (IL-6) in one-step and multistep postoperative patients in HD. Methods: Patients sample in total of 7 people (4 one-step surgery, 3 multistep surgery) taken from May to October 2022 at the Arifin Ahmad Hospital which were then examined for IL-6 at the LONTAR biomedical integrated laboratory, Faculty of Medicine Riau University. Plasma IL-6 levels were measured from postoperative venous blood samples examined using the sandwich ELISA method and the results were processed by statistical T-test to assess the difference IL-6 levels in the two types of surgery methods. Results: The average IL-6 level in patients using one-step surgery was 0,14 pg/mL – 47,92 pg/mL and the average IL-6 level in patients using multistep surgery was 0,98 pg/mL – 28,00 pg/mL. This study showed that the level of IL-6 with one-step surgery was higher than multistep surgery but there was no significant difference in terms of inflamatory marker’s especially Interleukin-6. Conclusion: Interleukin-6 levels as a mark of inflammatory factors in one-step or multistep Hirschprung’s disease surgery were not statistically significant. [ABSTRACT FROM AUTHOR]

• Improved pain after total knee arthroplasty may be related to alterations in IL-6. • 49% of patients had improved clinical pain 3-months after TKA surgery. • In patients with improved pain, IL-6 reactivity decreased from pre- to post-surgery. • Change in insomnia moderated the association between pain and IL-6 reactivity. • In patients with decreased insomnia, improved pain was related to a reduction in IL-6. Knee osteoarthritis (KOA) is linked to an enhanced release of interleukin-6 (IL-6). Increased levels of IL-6 are associated with greater pain and insomnia. While total knee arthroplasty (TKA) typically results in the reduction of pain, for a subgroup of patients, pain does not improve. Understanding patients' propensity to upregulate IL-6 may provide insight into variation in the clinical success of TKA for improving pain, and insomnia may play an important modulatory role. We investigated the association between pre- and post-surgical changes in clinical pain and IL-6 reactivity, and whether change in insomnia moderated this association. Patients (n = 39) with KOA came in-person before and 3-months after TKA. At both visits, patients completed validated measures of clinical pain and insomnia, as well as underwent quantitative sensory testing (QST). Blood samples were collected to analyze IL-expression both before and after QST procedures to assess changes in IL-6 in response to QST (IL-6 reactivity). Patients were categorized into two groups based on change in clinical pain from pre- to post-surgery: 1) pain decreased > 2 points (pain improved) and 2) pain did not decrease > 2 points (pain did not improve). Based on this definition, 49 % of patients had improved pain at 3-months. Among patients with improved pain, IL-6 reactivity significantly decreased from pre- to post-surgery, whereas there was no significant change in IL-6 reactivity among those whose pain did not improve. There was also a significant interaction between pain status and change in insomnia, such that among patients whose insomnia decreased over time, improved pain was significantly associated with a reduction in IL-6 reactivity. However, among patients whose insomnia increased over time, pain status and change in IL-6 reactivity were not significantly associated. Our findings suggest that the resolution of clinical pain after TKA may be associated with discernible alterations in pro-inflammatory responses that can be measured under controlled laboratory conditions, and this association may be moderated by perioperative changes in insomnia. Randomized controlled trials which carefully characterize the phenotypic features of patients are needed to understand how and for whom behavioral interventions may be beneficial in modulating inflammation, pain, and insomnia. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between groups, while IL-6 did not show a significant distinction. The iterative classification process improved model assumptions and classification accuracy, achieving a pre-classification accuracy of 71.8%, which adjusted to 57.1% post-classification. The results highlight DFA's potential in OA diagnosis, suggesting its utility in managing complex data and aiding personalised treatment strategies. The study underscores the need for larger sample sizes and additional biomarkers to enhance diagnostic robustness and provides a foundation for integrating DFA into clinical practice for early OA detection. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders. [ABSTRACT FROM AUTHOR]

Background/objectives: Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. Methods: To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Results: Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Conclusions: Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes.

To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, β = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, β = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, β = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, β = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025–234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways. [ABSTRACT FROM AUTHOR]

Background: A high body mass index (BMI) is known to be associated with high blood pressure. Levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 (IL-6) are also increased in hypertensive patients. The aim of this study was to determine the correlation of BMI with MMP-9, TIMP-1, and IL-6 based on blood pressure. Methods: The study design was cross-sectional with subjects aged >= 36 years, male and female and divided into 3 groups: group with normal blood pressure (NBP), group with controlled hypertension (CHT), and group with uncontrolled hypertension (UcHT). Height, weight, and blood pressure were measured, as well as serum levels of MMP-9, TIMP-1 and IL-6 using the ELISA method. The correlation was considered significant at p-value of < 0.05. Results: The BMI in group UcHT was higher than in the other groups. There was a positive correlation between BMI and MMP-9; BMI and TIMP-1; and BMI and IL-6 (r=0.480, p=0.007; r=0.620; p=0.000; r=374, p=0.042 respectively) in group UcHT. Conclusions: An increase in BMI is accompanied by an increase in levels of MMP-9, TIMP-1, and IL-6 in group UcHT, signifying that it is necessary to control BMI to maintain stable levels of MMP-9, TIMP-1, and IL-6, thereby keeping blood pressure under control. [ABSTRACT FROM AUTHOR]

Cannabis contains over 500 different compounds, including cannabinoids, terpenoids, and flavonoids. Cannabidiol (CBD) is a non-psychoactive constituent, whereas beta-caryophyllene (BCP) is one of most the well-known terpenoids of Cannabis sativa. In recent years, there has been an emerging idea that the beneficial activities of these compounds are greater when they are combined. The aim of this study was to evaluate the anti-inflammatory effect of CBD and BCP using the in vitro model of lipopolysaccharide (LPS)-stimulated human keratinocytes (HaCaT) cells. The vitality of the cells was quantified using LDH and MTT assays. The levels of the following pro-inflammatory proteins and genes were quantified: IL-1β, COX-2, and phospho-NF-κB p65 (p-p65) through Western blotting (WB) and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) through quantitative real-time polymerase chain reaction (RT-qPCR). When present in the incubation medium, CBD and BCP reduced the increased levels of pro-inflammatory proteins (IL-1β, COX-2, and p-NF-kB) induced by LPS. The anti-inflammatory effects of CBD were blocked by a PPARγ antagonist, whereas a CB2 antagonist was able to revert the effects of BCP. Selected concentrations of CBD and BCP were able to revert the increases in the expression of pro-inflammatory genes (IL-1β, IL-6, and TNFα), and these effects were significant when the drugs were used in combination. Our results suggest that CBD and BCP work in concert to produce a major anti-inflammatory effect with good safety profiles. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an essential role in tumor progression and in modulating tumor response to anticancer therapy. Cellular senescence leads to a switch in the cell secretome, characterized by the senescence-associated secretory phenotype (SASP), which may regulate tumorigenesis. Senolytic therapy is considered a novel anticancer strategy that eliminates the deleterious effects of senescent cells in the TME. Here, we show that two different types of senolytic drugs, despite efficiently depleting senescent cells, have opposite effects on cancer-associated fibroblasts (CAFs) and their ability to regulate epithelial–mesenchymal transition (EMT). We found that senolytic drugs, navitoclax and the combination of dasatinib/quercetin, reduced the number of spontaneously senescent and TNF-induced senescent CAFs. Despite the depletion of senescent cells, the combination of dasatinib/quercetin versus navitoclax increased the secretion of the SASP pro-inflammatory cytokine IL-6. This differential effect correlated with the promotion of enhanced migration and EMT in MC38 colorectal cancer cells. Our results demonstrate that some senolytics may have side effects unrelated to their senolytic activity and may promote tumorigenesis. We argue for more careful and extensive studies of the effects of senolytics on various aspects of tumor progression and tumor resistance to therapy before the senolytic strategy is implemented in the clinic. [ABSTRACT FROM AUTHOR]

COVID-19 has significantly affected people with pre-existing conditions, particularly those suffering from type 2 diabetes mellitus (T2DM), as it increases the risk of complications and mortality. The dysregulated inflammatory response in T2DM patients is a critical factor contributing to severe disease progression in these individuals. Recent research suggests that genetic variations, such as Rs657152 polymorphisms, could influence inflammatory markers and immune responses in T2DM patients infected with COVID-19. Understanding this genetic relationship is crucial for improving treatment strategies and predicting outcomes in this high-risk group. The present was designed to evaluate the correlation of Rs657152 gene polymorphisms with inflammatory markers in COVID-19 patients with T2DM. This study enrolled 91 participants, including 31 healthy individuals, 30 COVID-19 patients with T2DM, and 30 non-diabetic COVID-19 patients. Inflammatory markers (CRP, IL-6, D-dimer, and ferritin) were measured, and Rs657152 polymorphisms were genotyped. Statistical analysis was conducted using SPSS version 23. COVID-19 patients with T2DM showed significantly higher BMI, greater severity of COVID-19, and increased levels of inflammatory markers compared to non-diabetic patients. A significant correlation was observed between the Rs657152 polymorphisms and elevated levels of IL-6, D-dimer, and ferritin in T2DM patients (P<0.05). The polymorphisms of the Rs657152 gene may exacerbate the inflammatory response in COVID-19 patients with T2DM, contributing to increased severity of the disease. [ABSTRACT FROM AUTHOR]

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6’s involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6’s mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6’s interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.

Abstract Objective Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. Methods This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. Results Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P

West Nile virus (WNV) and Japanese encephalitis virus (JEV) are emerging mosquito-borne flaviviruses causing encephalitis globally. No specific drug or therapy exists to treat flavivirus-induced neurological diseases. The lack of specific therapeutics underscores an urgent need to determine the function of important host factors involved in flavivirus replication and disease progression. Interleukin-6 (IL-6) upregulation has been observed during viral infections in both mice and humans, implying that it may influence the disease outcome significantly. Herein, we investigated the function of IL-6 in the pathogenesis of neurotropic flavivirus infections. First, we examined the role of IL-6 in flavivirusinfected human neuroblastoma cells, SK-N-SH, and found that IL-6 neutralization increased the WNV or JEV replication and inhibited the expression of key cytokines. We further evaluated the role of IL-6 by infecting primary mouse cells derived from IL-6 knockout (IL-6-/-) mice and wild-type (WT) mice with WNV or JEV. The results exhibited increased virus yields in the cells lacking the IL-6 gene. Next, our in vivo approach revealed that IL-6-/- mice had significantly higher morbidity and mortality after subcutaneous infection with the pathogenic WNV NY99 or JEV Nakayama strain compared to WT mice. The non-pathogenic WNV Eg101 strain did not cause mortality in WT mice but resulted in 60% mortality in IL-6-/- mice, indicating that IL-6 is required for the survival of mice after the peripheral inoculation of WNV or JEV. We also observed significantly higher viremia and brain viral load in IL-6-/- mice than in WT mice. Subsequently, we explored innate immune responses in WT and IL-6-/- mice after WNV NY99 infection. Our data demonstrated that the IL-6-/- mice had reduced levels of key cytokines in the serum during early infection but elevated levels of proinflammatory cytokines in the brain later, along with suppressed antiinflammatory cytokines. In addition, mRNA expression of IFN-α and IFN-β was significantly lower in the infected IL-6-/- mice. In conclusion, these data suggest that the lack of IL-6 exacerbates WNV or JEV infection in vitro and in vivo by causing an increase in virus replication and dysregulating host immune response. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. Methods A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. Results The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P

Objective: Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. Methods: This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. Results: Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = − 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = − 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker. Conclusions: Elevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV) and Japanese encephalitis virus (JEV) are emerging mosquito-borne flaviviruses causing encephalitis globally. No specific drug or therapy exists to treat flavivirus-induced neurological diseases. The lack of specific therapeutics underscores an urgent need to determine the function of important host factors involved in flavivirus replication and disease progression. Interleukin-6 (IL-6) upregulation has been observed during viral infections in both mice and humans, implying that it may influence the disease outcome significantly. Herein, we investigated the function of IL-6 in the pathogenesis of neurotropic flavivirus infections. First, we examined the role of IL-6 in flavivirus-infected human neuroblastoma cells, SK-N-SH, and found that IL-6 neutralization increased the WNV or JEV replication and inhibited the expression of key cytokines. We further evaluated the role of IL-6 by infecting primary mouse cells derived from IL-6 knockout (IL-6−/−) mice and wild-type (WT) mice with WNV or JEV. The results exhibited increased virus yields in the cells lacking the IL-6 gene. Next, our in vivo approach revealed that IL-6−/− mice had significantly higher morbidity and mortality after subcutaneous infection with the pathogenic WNV NY99 or JEV Nakayama strain compared to WT mice. The non-pathogenic WNV Eg101 strain did not cause mortality in WT mice but resulted in 60% mortality in IL-6−/− mice, indicating that IL-6 is required for the survival of mice after the peripheral inoculation of WNV or JEV. We also observed significantly higher viremia and brain viral load in IL-6−/− mice than in WT mice. Subsequently, we explored innate immune responses in WT and IL-6−/− mice after WNV NY99 infection. Our data demonstrated that the IL-6−/− mice had reduced levels of key cytokines in the serum during early infection but elevated levels of proinflammatory cytokines in the brain later, along with suppressed anti-inflammatory cytokines. In addition, mRNA expression of IFN-α and IFN-β was significantly lower in the infected IL-6−/− mice. In conclusion, these data suggest that the lack of IL-6 exacerbates WNV or JEV infection in vitro and in vivo by causing an increase in virus replication and dysregulating host immune response.

Introduction: The seeds of Brucea javanica (L.) Merr. (BJ) have been traditionally used to treat various types of cancers for many years in China. In this study, we systematically investigated a BJ oil emulsion (BJOE) produced from BJ seeds with the purpose of evaluating its antiviral effect against hepatitis B virus (HBV). Methods: HepG2.215 (a wild-type HBV cell line), HepG2, and Huh7, transfected with wildtype (WT) or lamivudine-resistance mutant (LMV-MT) HBV replicon plasmids, were treated with different doses of BJOE and then used for pharmacodynamic evaluation. Cell viability was determined using CCK8 assay. The levels of HBsAg/HBeAg in cell cultured supernatant, HBcAg in cell lysis solution, and HBV DNA in both were evaluated. Results: BJOE at =5 mg/ml was nontoxic to carcinoma cell lines, but could significantly inhibit WT/LMV-MT HBV replication and HBs/e/c antigen expression in a dose-dependent manner by upregulating interleukin-6 (IL-6), demonstrating that it possesses moderate anti-HBV activity. As one of the major components of BJOE, bruceine B was found to play a dominant role in IL-6 induction and HBV inhibition. Discussion: Our results demonstrated that BJOE suppressed HBV replication by stimulating IL-6, indicating that it has promising clinical therapeutic potential for both WT and LMV-MT HBV. [ABSTRACT FROM AUTHOR]

Recurrent vascular events after stroke are common despite contemporary therapies and there is an unmet clinical need for improved secondary prevention. Inflammation is a probable causal factor in first and recurrent stroke and is a promising therapeutic target. Blood biomarkers of inflammation may also improve risk stratification and patient selection for intensive prevention therapies. We review the pathogenic role of inflammation in stroke and atherosclerosis, examining data from observational and genetic studies as well as randomized controlled trials of anti-inflammatory agents in stroke and cardiac disease. We discuss the potential applications for inflammatory biomarkers in stroke care and evaluate some of the uncertainties and controversies in this field.

Background: The role and regulation mechanisms of the interleukin-6 and 10 (IL6 and IL-10) serum levels and the interaction between CD4+ and CD8+ lymphocytes with SARS-COV-2 IgM and IgG in the context of COVID-19 infection are not fully understood. Methods: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively. Results: The male ratio and mean age of critically ill patients' group were significantly higher in compared to controls (P< 0.05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0.002, 0.001), but IL-6 promoter methylation was not significantly decreased in patients (P=0.835). The IL-10 promoter methylation and expression were not different between cases and controls (0.326, 0.455), but serum IL-10 levels were higher in patients (P< 0.001). The CD4+ and CD8+ lymphocytes decreased (P< 0.001) and mean SARS-COV-2 IgG increased (P=0.002) in the patients compared to controls. Conclusions: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. Methods: A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. Results: The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P < 0.05) and value of IL-6 was significantly decreased (P < 0.05) at the corresponding time points. Compared with group C, the MoCA score on day 7 after surgery in Group T was significantly higher (P < 0.05). Conclusion: Compared with the traditional ventilation strategy, the individualized ΔP combined with LUS-based PEEP titration in patients with COPD during the perioperative period of laparoscopic surgery can play a better role in lung protection and can improve postoperative cognitive function. [ABSTRACT FROM AUTHOR]

ObjectiveIt is unclear whether the mechanism of the interleukin (IL)-6 signaling pathway is similar between granulomatous lobular mastitis (GLM) and benign breast tumors. This study aimed to explore the differences and significance of peripheral blood IL-6 and related cytokines, routine blood test results, and C-reactive protein (CRP) levels between patients with GLM and benign breast tumors.MethodsSeventy-three inpatients with GLM who underwent surgery and 60 patients with benign breast tumors diagnosed based on pathological findings between November 2022 and May 2023 were included. The white blood cell (WBC) and neutrophil (NEU) counts were determined using an automatic blood cell analyzer, the CRP level was determined by an immunoturbidimetric assay, and serum IL-6 and related cytokine levels were determined by an enzyme-linked immunosorbent assay.ResultsThe WBC, NEU, and CRP values in patients with GLM were significantly higher than those in patients with benign breast tumors (P < 0.01). Serum IL-6 levels were significantly higher in patients with GLM than in those with benign breast tumors (P < 0.01). There were no significant differences in the serum concentrations of IL-1β, IL-7, and interferon (IFN)-γ between patients with GLM and those with benign breast tumors (P > 0.05), but the tumor necrosis factor (TNF)-α level was higher in patients with GLM than in those with benign breast tumors (P < 0.01). In patients with GLM, the Pearson correlation analysis showed that the IL-6 level was positively correlated with NEU, NEU%, CRP, IL-17, and TNF-α values (P < 0.01). Additionally, the IL-6 level was weakly positively correlated with WBC and IFN-γ values. Conversely, in patients with benign breast tumors, the IL-6 level was not significantly correlated with the aforementioned indicators in routine blood tests but was positively correlated with IL-17, IFN-γ, and TNF-α values (P < 0.01).ConclusionsIL-6, NEU, NEU%, and CRP values were significantly elevated in patients with GLM compared to those with benign breast tumors, indicating that IL-6 plays an important role in the development and onset of GLM. The correlation between these cytokines and the development and progression of benign breast tumors needs to be further explored, as cytokines such as IL-6 may provide effective markers for the treatment of GLM.