Interleukin-6 Levels Research Articles

The possibility of using synovial C-reactive protein, interleukin-6 and presepsin in the diagnosis of periprostheticjoint infection.

The diagnosis of infectious complications in joint prosthetics remains a pressing issue, especially in cases where pathogens do not grow during the seeding of biological material. This study analyzed the potential use of synovial biomarkers for the diagnosis of periprosthetic infections (PPI), based on literature data. The aim was to determine the significance of synovial C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin in diagnosing PPI. Materials and methods: A prospective, single-center, blinded study was conducted on patients undergoing revision arthroplasty for both infectious and aseptic inflammation in the endoprosthetic area. The study included 66 patients, divided into two groups: Group I included 17 patients with periprosthetic infection diagnosed according to the ICM Philly criteria of 2018; and Group II included 49 patients with aseptic inflammation in the endoprosthetic region.Synovial fluid samples from all participants were analyzed for bacteriological and cytological analysis to determine the levels of CRP, IL-6, and presepsin. Receiver operating characteristic (ROC) analysis was performed to determine sensitivity, specificity, and accuracy, as well as thresholds for laboratory data. Results: The greatest reliability for diagnosing infectious and aseptic inflammations was shown for the number of leukocytes in synovial fluids, with an area under the curve (AUC) of 0,928 (95% confidence interval [CI]: 0,837-0,977; p0,0001), as well as for synovial CRP with an AUC of 0,776 (95% CI: 0,656-0,87; p=0,0004), and IL-6 with an AUC of 0,712 (95% CI: 0,583-0,82, p=0,0048). While the presepsin level was significantly different between groups, AUC was 0,582 (95% CI: 0,453-0,703, p=0,3344). Threshold values were calculated for CRP at 5,6 mg/L and presepsin – 1212,0 pg/mL and IL-6 – 988,5 pg/mL. The sensitivity, specificity, and accuracy of the diagnosis of PPI were 62,5%, 85,71%, and 80%, respectively for CRP; 68,5%, 63,04%, and 68,7% for IL-6; and 43,75%, 79,59%, and 70,77% for presepsin. Conclusion: IL-6 has the highest sensitivity for PPI, but it has lower accuracy and specificity than CRP. Presepsin has the lowest sensitivity, specificity and accuracy for the diagnosis of PPI.

Mechanism of Asperosaponin VI Related to EGFR/MMP9/AKT/PI3K Pathway in Treatment of Rheumtoid Arthritis.

To explore the mechanism of action of asperosaponin VI (AVI) in the treatment of rheumatoid arthritis (RA) and validate it in ex vivo experiments using network pharmacology and molecular docking methods. The predicted targets of AVI were obtained from PharmMaper, UniProt and SwissTarget Prediction platforms, the disease targets were collected from Online Mendelian Inheritance in Man, Therapeutic Target Database and GeneCards databases, the intersection targets of AVI and RA were obtained from Venny 2.1.0, and the protein-protein interaction (PPI) network was obtained from STRING database, which was analyzed by Cytoscape software and screened to obtain the core targets. Cytoscape software was used to analyze PPI network and screen the core targets. Based on the Database for Annotation, Visualization and Integrated Discovery database, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed, and Cytoscape software was used to construct the "Disease-Pathway-Target-Drug" network, which was finally verified by molecular docking and animal experiments. Network pharmacological studies showed that AVI was able to modulate 289 targets, with 102 targets for the potential treatment of RA, with the core pathway being the AKT/PI3K signaling pathway, and the core targets being the epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9). Molecular docking results showed that AVI could produce strong binding with both of the 2 core targets. In vitro cellular experiments showed that AVI reduced nitric oxide, prostaglandin E2, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 β levels (P<0.05) and inhibited cyclooxygenase-2, nitric oxide synthase, EGFR, MMP9, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated serine-threonine kinase (p-AKT) proteins (P<0.05). The results of in vivo studies showed that AVI improved RA score and foot swelling thickness and decreased TNF-α, IL-6, p-PI3K and p-AKT levels in RA rats (P<0.05). AVI exerts anti-inflammatory and anti-RA effects which might be related to the EGFR/MMP9/AKT/PI3K pathway.

Regulatory Effect of Fucoidan Hydrolysates on Lipopolysaccharide-Induced Inflammation and Intestinal Barrier Dysfunction in Caco-2 and RAW264.7 Cells Co-Cultures

Fucoidan, a sulfated polysaccharide rich in fucose, is derived from brown algae and marine invertebrates. Multiple bioactivities have been shown with fucoidan, while growing attraction has emerged in its low-molecular-weight (Mw) hydrolysates. Here, the anti-inflammatory effect of fucoidan, low-Mw acidolyzed fucoidan (LMAF, &lt;1.5 kDa), and high-Mw acidolyzed fucoidan (HMAF, 1.5–20 kDa) were investigated in vitro using lipopolysaccharide (LPS)-stimulated Caco-2 and RAW264.7 co-cultures. Fucoidan, LMAF, and HMAF with different structures exhibited varied anti-inflammatory effects. LMAF and HMAF effectively decreased the nitric oxide release of RAW264.7 cells. LMAF exhibited a competitive effect in reducing tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 levels compared to HMAF and fucoidan. Transcriptome of RAW264.7 revealed that LPS and LMAF mainly regulated the transcriptional expression of genes, including Tnf, Il6, Il1b, Junb, and Nfkb1 in the TNF signaling pathway, NF-kappa B signaling pathway, and cytokine–cytokine receptor interaction. RT-PCR results indicated that LMAF markedly reduced the LPS-elevated expression of Cxcl2, Tnf, Ccl2, Il1b, and Csf2. Moreover, LMAF effectively increased the proteins expression of Claudin-1, Occludin, and Zonula occluden-1 in Caco-2 cells. This study highlights the potential of LMAF to improve inflammation and intestinal barrier integrity, offering a foundation for further application of low-Mw fucoidan hydrolysates.

The Impact of ERAS and Multidisciplinary Teams on Perioperative Management in Colorectal Cancer.

The Enhanced Recovery After Surgery (ERAS) protocol, a comprehensive multimodal approach, aims to mitigate surgical stress, expedite recovery, and improve postoperative outcomes. Its implementation has notably advanced perioperative care in colorectal cancer surgeries. Integrating ERAS with multidisciplinary collaboration, involving surgery, anesthesia, nursing, and nutrition, may further enhance patient outcomes, making it a significant focus in clinical practice. This study assessed the effectiveness of integrating the ERAS model with multidisciplinary collaboration during the perioperative period in colorectal cancer patients. A total of 117 patients scheduled for elective surgery at Haiyan People's Hospital between August 2023 and April 2024 were randomly assigned to either a control group (n = 59), receiving traditional care, or an experimental group (n = 58), receiving ERAS-based multidisciplinary care. Key outcomes related to postoperative rehabilitation were evaluated. Patients in the ERAS group demonstrated significantly shorter hospital stays, quicker catheter removal, and earlier mobilization compared to the control group (P < 0.0001 for all). Additionally, the ERAS group exhibited reduced postoperative inflammatory responses, as indicated by significantly lower interleukin-6 levels on the first postoperative day (P = 0.0247). The quality of life was significantly higher in the ERAS group (P < 0.05). Furthermore, the ERAS group incurred lower total hospitalization expenses than the control group (P = 0.0011). These findings confirm the benefits of the ERAS protocol in enhancing postoperative recovery in colorectal cancer surgeries. The study highlights the importance of a multidisciplinary approach in optimizing patient outcomes and reducing the burden on hospital resources.

Fibrinogen-Like Protein 2 Protects the Aggravation of Hypertriglyceridemia on the Severity of Hypertriglyceridemia Acute Pancreatitis by Regulating Macrophages.

The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163. The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.

Petunidin attenuates vinclozolin instigated testicular toxicity in albino rats via regulating TLR4/MyD88/TRAF6 and Nrf-2/Keap-1 pathway: A pharmacodynamic and molecular simulation approach

Vinclozolin (VZN) is a widely used fungicide which exerts deleterious impacts on various organs including testis. Petunidin (PDN) is a polyphenolic compound that demonstrates a broad range of pharmacological activities. Thirty-two rats were divided into 4 groups including the control, VZN (100 mg/kg), VZN (100 mg/kg) + PDN (4 mg/kg) and PDN (4 mg/kg) treated group. The activities of antioxidant enzymes were assessed by using previously documented protocols. The gene expressions were determined by using qRT-PCR. The levels of hepatic function and apoptotic markers were evaluated by using standard ELISA technique. The histological analysis was carried out as per the standard protocol of histology. It was revealed that VZN disrupted the Nrf-2/Keap-1 pathway. Moreover, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (HO-1) and glutathione reductase (GSR) were reduced whereas levels of reactive oxygen species (ROS) & malondialdehyde (MDA) were promoted following the VZN intoxication. Furthermore, VZN intoxication reduced total sperm count, viability, motility as well as luteinizing hormone (LH), follicle stimulating hormone (FSH), and plasma testosterone. Besides, administration of VZN decreased the expressions of 3β-Hydroxysteroid dehydrogenase (3β-HSD), steroidogenic acute regulatory protein (StAR) and 17β-Hydroxysteroid dehydrogenase (17β-HSD). Moreover, VZN exposure escalated the expressions of Bcl-2–associated X protein (Bax) and cysteine–aspartic acid protease-3 (Caspase-3) while reducing the expressions of B-cell lymphoma-2 (Bcl-2). Additionally, VZN administration increased the gene expression of toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and myeloid differentiation primary response 88 (MyD88). The levels of interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2) were promoted following the VZN administration. Furthermore, VZN intoxication disrupted the normal histology of testicular tissues. However, VZN + PDN treatment ameliorated testicular damage via regulating aforementioned dysregulations owing to its anti-inflammatory, antioxidative as well as anti-apoptotic potentials. Lastly, molecular docking (MD) was performed to assess the effectiveness of PDN as a curative compound by analyzing its binding affinity with the targeted proteins (Keap1, TLR4 and StAR). Our in-silico evaluations confirmed that PDN possesses the potential to interact with binding pockets of these proteins, emphasizing its capability as a curative compound to mitigate VZN-prompted reproductive damage.

Autonomic and Immune Stress Response Networks in Patients Living With HIV.

Stress response systems are frequently dysregulated in patients with chronic inflammatory disorders. Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. However, these connections have not been examined in humans. We hypothesized that the subtype and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics in people living with HIV. This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10). Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman's rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017). Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.

The Effects of Albumin 20% and Hydroxyethyl Starch 6% on Bleeding and Interleukin-6 Levels as Priming Solutions for Cardiopulmonary Bypass: A Randomized Controlled Trial

Background: Cardiopulmonary bypass (CPB) can adversely affect coagulation and systemic inflammatory response. Given that the optimal strategy for priming CPB in cardiac surgery remains a matter of debate, this study aimed to investigate the effects of albumin 20% and hydroxyethyl starch 6% as priming solutions on bleeding and interleukin-6 (IL-6) levels during CPB. Methods: This randomized clinical trial involved 40 patients undergoing coronary artery bypass surgery at Shahid Chamran Hospital between July 2021 and July 2022. Participants were assigned to 2 groups: the first group received 50 mL of albumin 20% as the priming solution for the CPB circuit, while the second group received 500 mL of hydroxyethyl starch 6%. Bleeding and IL-6 levels were assessed before and after the intervention. Results: The albumin group comprised 80.0% men and 20.0% women, with a mean age of 66.45±5.84 years. The hydroxyethyl starch 6% group consisted of 85.0% men and 15.0% women, with a mean age of 63.05±5.92 years (P&gt;0.05). The findings revealed that 12 hours after CPB, the IL-6 level in the hydroxyethyl starch 6% group (mean: 171.6±77.71 pg/mL) was significantly higher than that in the albumin group (mean: 105.8±36.45 pg/mL; P=0.002). At 48 hours after CPB, the mean bleeding was not significantly different between the groups (P=0.950). Conclusion: Albumin 20% was more effective than hydroxyethyl starch 6% concerning IL-6 levels. However, no significant differences in bleeding were observed between the groups at 48 hours post-CPB.

Efficacy of Clarithromycin Combined with Fluticasone Propionate on Nasal Function, Nasal Mucociliary Transport Function, and Serum Inflammatory Markers in Chronic Rhinosinusitis Patients After Functional Endoscopic Sinus Surgery.

Objective: This study aims to assess the efficacy of clarithromycin (CAM) combined with fluticasone propionate (FP) in patients with chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS), focusing on nasal function, nasal mucociliary transport (MCT) function, and serum inflammatory markers. Methods: The control group (n = 48) was treated with FESS alone, while the study group (n = 48) was treated with FESS plus CAM combined with FP. The clinical effects, symptom scores, nasal function, nasal MCT function, serum inflammatory marker levels, and the occurrence of adverse reactions were compared. Results: The total efficacy rate of the study group (95.83%) was significantly higher than that of the control group (83.33%). After treatment, the study group showed lower symptom scores for nasal congestion, runny nose, sneezing and dizziness, and headache compared to those in the control group. The study group also had lower nasal airway resistance, shorter distance from the minimal cross-sectional area to the nostril, and lower T&T olfactory scores. In contrast, their nasal cavity volume and minimal cross-sectional area were higher than those of the control group. Additionally, the nasal mucociliary clearance and MCT rates were higher in the study group. Serum levels of interleukin-6, interleukin-8, tumor necrosis factor-α, and procalcitonin were significantly lower in the study group compared to the control group (all P < .05). Conclusion: The use of CAM combined with FP in patients after FESS for CRS is effective, leading to the relief of clinical symptoms, improvement of nasal function, enhancement of MCT function, and reduction of inflammatory response, without increasing the incidence of adverse reactions.

The effect of twelve weeks of high-intensity functional training and Ginkgo biloba consumption on the serum levels of some inflammatory cytokines in operational male firefighters of Yazd city

Introduction: functional exercises and consumption of the medicinal plant Ginkgo biloba, a natural source of flavonoids and polyphenolic compounds, have beneficial effects in improving the inflammatory state and physical performance of people exposed to occupational stress. Therefore, the aim of the present study was to investigate the effect of 12 weeks of high-intensity functional training and consumption of Ginkgo biloba extract on the serum levels of interleukin-8 and interleukin-1β in operational male firefighters of Yazd city. Materials and Methods: For this purpose, 48 male firefighters were randomly divided into four groups including high-intensity functional training (HIFT), high-intensity functional training with ginkgo biloba consumption, ginkgo biloba extract consumption, and control-placebo. The training was carried out for 12 weeks and 4 sessions per week. Ginkgo biloba extract (80 mg) was administered as two capsules once a day after breakfast for 12 weeks. Blood samples were taken before and 48 hours after the last training session. Data were analyzed using two-way analysis of variance with SPSS-26 software. Results: The results showed that the interaction effect of exercise and ginkgo biloba extract, as well as the effect of exercise and ginkgo biloba extract alone, caused a significant decrease in the serum levels of interleukin-8 and interleukin-1β (p&lt;0.05). The highest percentage of changes in interleukin-8 and interleukin-1β were obtained following exercise intervention along with the consumption of Ginkgo biloba extract. Conclusion: Performing high-intensity functional exercises with Ginkgo biloba extract had the greatest effect in reducing serum levels of inflammatory indicators and improving oxidative stress conditions in firefighters.

Construction and validation of a risk prediction model for postoperative lung infection in elderly patients with lung cancer.

This study aimed to analyze the risk factors for postoperative lung infection in elderly patients with lung cancer (LC) and construct a predictive model. A retrospective analysis was conducted on 192 elderly patients with LC who underwent surgical treatment in our hospital between February 2020 and May 2023. According to whether there is lung infection after surgery, they were divided into an infected group (n = 55) and a noninfected group (n = 137). Binary logistic regression was used to analyze factors influencing postoperative lung infection in elderly patients with LC. Based on the logistic regression results, a predictive model for postoperative lung infection in LC patients was constructed. The receiver operating characteristic curve was used to analyze C-reactive protein (CRP), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), and their combination in predicting postoperative lung infection in patients with LC. There were significant differences between the infected group and the noninfected group in age, smoking history, diabetes, and perioperative antibiotic use were significantly different between the infected and noninfected groups (P < .05). The postoperative CRP, IL-6, and IGF-1 levels in the infected group were higher than those in the noninfected group on the 1st day (P < .05). Logistic regression analysis showed that age > 70 years, history of smoking, history of diabetes, prolonged use of perioperative antibiotics, and elevated CRP, IL-6, and IGF-1 levels on the 1st day after surgery were risk factors for postoperative lung infection in elderly patients with LC (P < .05). Receiver operating characteristic curve analysis showed that the area under curve values of CRP, IL-6, IGF-1, and their combination in predicting postoperative lung infection in elderly patients with LC were 0.701, 0.806, 0.737, and 0.871, P < .05), with sensitivity values of 0.443, 0.987, 0.456, and 0.835, respectively; the specificity was 0.978, 0.525, 0.991, and 0.821, respectively. Age > 70 years, smoking history, diabetes history, prolonged use of perioperative antibiotics, and elevated CRP, IL-6, and IGF-1 levels on the 1st day after surgery have an impact on postoperative lung infection in elderly patients with LC. Early postoperative monitoring of changes in CRP, IL-6, and IGF-1 levels can provide an important reference for predicting the occurrence of postoperative lung infections.

Overexpression of YKL40,IL-6, IL-8, TNF-α in tonsils and the role of YKL40 in childhood with obstructive sleep apnea syndrome

To evaluate the levels of YKL40, IL-6(interleukin-6), IL-8(interleukin-8), IL-10(interleukin-10), TNF-α (tumor necrosis factor-α) in OSAS (obstructive sleep apnea syndrome)children and explore the mechanism of YKL40 promoting inflammatory factors overexpression in tonsils. qPCR and ELISA were used to identify the expression of YKL40, IL-6, IL-8, IL-10, and TNF-α in the tonsils of OSAS children. Primary tonsil lymphocytes (PTLCs) were cultured and recombinant human YKL40(rhYKL40)was used to stimulate PTLCs in different concentrations and at different time points. The activation of NF-κB in PTLCs was screened by western blotting. Relative mRNA of YKL40, IL-6, IL-8, TNF-α was over expressed in OSAS-derived tonsil tissue and the levels of YKL40, IL-6, IL-8, and TNF-α was increased in OSAS-derived protein supernatant of tonsil tissue.The relative mRNA expression of IL-6, IL-8 and TNF-α increased under the treatment of YKL40 (100 ng/mmol for 24 h). The phosphorylation of p65 in NF-κB pathway was stimulated in the process. The levels of YKL40, IL-6, IL-8, and TNF-α increases in OSAS children, and YKL40 promotes the overexpression of IL-6, IL-8 and TNF-α in PTLCs via NF-κB pathway. The result implements that inflammation may play an important role in the pathogenesis of OSAS in children.

Immunomodulatory Potential of Melatonin in Immunosuppression: An in-vivo Study.

To assess the immunomodulatory effects of melatonin on the acquired immunity of immunosuppressed male Wistar rats by checking Interleukin 6 (IL-6) levels, total leucocyte counts (TLC), and differential leucocyte counts. Experimental study. Place and Duration of the Study: Animal laboratory, CMH Lahore Medical College, from June to October 2023. Fifty male Wistar rats, weighing 180g to 200g, were included in this study with 10 rats in each of the five groups namely cyclophosphamide (CP), CP + melatonin, CP + immunomodulator, melatonin-only, and control. A calculated dose of CP was administered intraperitoneally for 30 days (from 13/06/23 to 13/07/23) to each group except the control groups. After this, the experimental group was given melatonin CP + Melatonin for 7 days (from 14/07/23 to 20/07/23). CP + Immunomodulatory group was kept for comparison of immunomodulatory effects. Blood samples were drawn from all 5 groups. IL-6 was estimated through ELISA. Other parameters assessed were TLC and absolute differential leucocyte counts. Melatonin increased IL-6 levels significantly (p = 0.042) as well as the TLC levels (p <0.001) compared to the immuno-suppressed CP group. Melatonin was seen to have an upregulation of IL-6 levels in immunosuppression compared to the administration of immunomodulator preparation (p = 0.506) which was not as effective. Administration of melatonin significantly increased the TLC, neutrophil, lymphocyte, monocyte, and eosinophil count compared to known immunomodulators. Melatonin as a supplement may have some role in activating multiple immune response processes in immune-depressed states. It was also established that it allows quick recovery of cell components from immunosuppressed states. Melatonin, Immunomodulation, Rats, Interleukin-6, Acquired immunity, Cyclophosphamide.

Immunomodulatory Potential of Melatonin in Immunosuppression: An in-vivo Study.

To assess the immunomodulatory effects of melatonin on the acquired immunity of immunosuppressed male Wistar rats by checking Interleukin 6 (IL-6) levels, total leucocyte counts (TLC), and differential leucocyte counts. Experimental study. Place and Duration of the Study: Animal laboratory, CMH Lahore Medical College, from June to October 2023. Fifty male Wistar rats, weighing 180g to 200g, were included in this study with 10 rats in each of the five groups namely cyclophosphamide (CP), CP + melatonin, CP + immunomodulator, melatonin-only, and control. A calculated dose of CP was administered intraperitoneally for 30 days (from 13/06/23 to 13/07/23) to each group except the control groups. After this, the experimental group was given melatonin CP + Melatonin for 7 days (from 14/07/23 to 20/07/23). CP + Immunomodulatory group was kept for comparison of immunomodulatory effects. Blood samples were drawn from all 5 groups. IL-6 was estimated through ELISA. Other parameters assessed were TLC and absolute differential leucocyte counts. Melatonin increased IL-6 levels significantly (p = 0.042) as well as the TLC levels (p <0.001) compared to the immuno-suppressed CP group. Melatonin was seen to have an upregulation of IL-6 levels in immunosuppression compared to the administration of immunomodulator preparation (p = 0.506) which was not as effective. Administration of melatonin significantly increased the TLC, neutrophil, lymphocyte, monocyte, and eosinophil count compared to known immunomodulators. Melatonin as a supplement may have some role in activating multiple immune response processes in immune-depressed states. It was also established that it allows quick recovery of cell components from immunosuppressed states. Melatonin, Immunomodulation, Rats, Interleukin-6, Acquired immunity, Cyclophosphamide.

Evaluation of the Relationship Between Salivary Adipokine Levels With Appetite and Anthropometric Indices in Patients With Type 2 Diabetes.

This study aimed to evaluate the association between salivary adipokine levels, including leptin, chemerin, resistin and interleukin-6, with body mass index (BMI), waist and wrist circumference and appetite in patients with type 2 diabetes. In this cross-sectional study, 104 participants were divided into three groups: 35 diabetic patients, 35 pre-diabetic individuals and 34 healthy controls. Unstimulated saliva samples were collected using the spitting method, and salivary levels of leptin, chemerin, resistin and interleukin-6 were measured via ELISA. Appetite was assessed using a standard questionnaire, and BMI, waist and wrist circumferences were measured with a tape measure. Statistical analysis was performed using SPSS 26, with a significance threshold set at 0.01. Significant differences were found in the salivary levels of leptin, chemerin, and resistin among the three groups (p < 0.01), but no significant difference was observed in the salivary levels of interleukin-6 (p > 0.01). Analysis also revealed significant differences in appetite traits among the groups, with the highest appetite trait observed in pre-diabetic subjects (p = 0.0002). The salivary level of chemerin was significantly associated with appetite traits regardless of diabetic status (p = 0.009). Appetite was also significantly related to BMI (p = 0.002) and waist circumference (p = 0.001) in all subjects. However, no significant relationship was observed between appetite and fasting plasma glucose or HbA1c levels (p > 0.01). The results of this study indicate that salivary levels of certain adipokines, such as leptin, chemerin and resistin, may be significantly higher in diabetic patients, although this is not true for all adipokines. While pre-diabetic patients exhibited a higher level of appetite, no positive correlation was found between salivary adipokine levels (except chemerin) and appetite or anthropometric characteristics, irrespective of diabetic status.

Regulatory mechanism of TRIM21 in sepsis-induced acute lung injury by promoting IRF1 ubiquitination.

Sepsis-induced acute lung injury (ALI) is characterized by inflammatory damage to pulmonary endothelial and epithelial cells. The aim of this study is to probe the significance and mechanism of tripartite motif-containing protein 21 (TRIM21) in sepsis-induced ALI. The sepsis-induced ALI mouse model was established by cecum ligation and puncture. The mice were infected with lentivirus and treated with proteasome inhibitor MG132. The lung respiratory damage, levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), IL-10 and pathological changes were observed. The expression levels of TRIM21, interferon regulatory factors 1 (IRF1) and triggering receptor expressed on myeloid cells 2 (TREM2) were measured and their interactions were analysed. The ubiquitination level of IRF1 was detected. TRIM21 and TREM2 were downregulated and IRF1 was upregulated in sepsis-induced ALI mice. TRIM21 overexpression eased inflammation and lung injury. TRIM21 promoted IRF1 degradation via ubiquitination modification. IRF1 bonded to the TREM2 promoter to inhibit its transcription. Overexpression of IRF1 or silencing TREM2 reversed the improvement of TRIM21 overexpression on lung injury in mice. In conclusion, TRIM21 reduced IRF1 expression by ubiquitination to improve TREM2 expression and ameliorate sepsis-induced ALI.

Comparison of clinical characteristics, microvascular complications and inflammatory markers in type 2 diabetic patients under insulin versus metformin treatment: A cross-sectional study at Karbala Diabetic Center, Iraq.

Type 2 diabetes mellitus (T2DM) is a major global health issue associated with chronic inflammation, which contributes to both disease progression and its complications, including cardiovascular and microvascular disorders. Key inflammatory markers such as tumor necrosis factor-alpha, interleukin-6 (IL-6), E-selectin, and P-selectin are elevated in T2DM patients and are implicated in the development of these complications. Understanding how treatments such as insulin and metformin affect these markers is crucial for improving therapeutic strategies in T2DM. This study investigated the effects of insulin and metformin on these inflammatory markers in T2DM patients. This was a cross-sectional study involving patients with diabetes on insulin (group A), metformin only (group B), and healthy controls (group C). Participants were enrolled from the Diabetic Center in Karbala, Iraq and underwent clinical assessments including ophthalmologic examinations. Fasting blood glucose, HbA1c and lipids levels were assessed. The levels of inflammatory markers (IL-6 and TNF-α), and adhesion molecules (sE-selectin and sP-selectin) were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The study included 522 patients with diabetes: 356 receiving insulin (group A), 70 receiving metformin (group B) and 96 healthy controls (group C). T2DM patients treated with insulin exhibited significantly more microvascular complications than those treated with metformin. Higher rates of retinopathy (64.3% vs 11.4%) and neuropathy (69.9% vs 11.4%) were observed in the insulin group, whereas the incidence of nephropathy did not differ significantly (14.6% vs 11.4%). Inflammatory markers were lower in the insulin group: TNF-α levels were 3-fold lower and IL-6 levels were 8-fold lower. Conversely, sE-selectin levels were 1.5-fold higher in the insulin group, and sP-selectin levels were 1.4-fold higher in the metformin group. This study highlights distinct differences in inflammatory markers and systemic complications between T2DM patients treated with insulin and those treated with metformin alone. Further research is needed to explore the mechanisms underlying these observations and optimize treatment strategies for T2DM patients.

Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial

BackgroundDeveloping interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.MethodsEighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis.ResultsThe RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups.ConclusionsIn this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD.Trial registrationThe trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 (https://www.clinicaltrials.gov/ct2/show/NCT04744922).

The Role of Interleukin-8 in the Estimation of Responsiveness to Steps 1 and 2 of Periodontal Therapy.

To investigate the association between interleukin-8 (IL-8) levels in gingival crevicular fluid (GCF) and total oral fluid (TOF) and the responsiveness to steps 1 and 2 of periodontal therapy. One-hundred and fifty-nine patients affected by periodontitis received steps 1 and 2 of periodontal therapy. At baseline, TOF and GCF samples were collected and analysed for IL-8 (Il-8TOF/IL-8GCF) using flow cytometry. Therapy outcomes were relative proportions of residual periodontal pockets (PPD%), pocket closure (PC) rates and pocket probing depth (PPD) reductions; these were associated with IL-8TOF/IL-8GCF. High IL-8TOF was significantly associated with higher residual PPD% (p = 0.044) and lower PPD reduction compared to low IL-8TOF (high 0.79 ± 1.20 mm vs. low 1.20 ± 1.20 mm, p < 0.001) in non-smokers, while in smokers high IL-8GCF was related to lower PPD reduction (high 0.62 ± 1.22 mm vs. low 0.84 ± 1.12 mm, p = 0.009). Furthermore, high baseline IL-8TOF was significantly associated with poorer PC rates compared to medium and low concentrations in both non-smokers (high 41% vs. medium 55% vs. low 58%, p < 0.001) and smokers (high 34% vs. medium 44% vs. low 46%, p < 0.001). High IL-8 concentrations at baseline had a significant impact on residual PPD%, PC rates and PPD reduction. The findings suggest that, especially in non-smokers, baseline IL-8 levels collected from the TOF could serve as a component in the estimation of responsiveness to steps 1 and 2 of periodontal therapy.

An NLR family member X1 mutation (p.Arg707Cys) suppresses hepatitis B virus infection in hepatocytes and favors the interaction of retinoic acid-inducible gene 1 with mitochondrial antiviral signaling protein.

NLR family member X1 (NLRX1) is an important member of the NOD-like receptor (NLR) family and plays unique roles in immune system regulation. Patients with hepatitis B virus (HBV) infection are more likely to have the NLRX1 mutation p.Arg707Cys than healthy individuals. It has been reported that NLRX1 increases the infection rate of HBV in HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). However, the role of NLRX1 mutation (p.Arg707Cys) in hepatitis remains unclear. We constructed Huh7 cells that stably overexpressed NTCP, using LV003 lentivirus. First, wild-type (WT) and mutant (MT) NLRX1 overexpression plasmids were constructed. The MT plasmid contained a point mutation at position 707 of the WT overexpression plasmid. Then, Huh7-NTCP cells were transfected with the WT or MT NLRX1 overexpression plasmid, and subsequent NLRX1 expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. HBV RNA levels were determined using RT-qPCR. HBsAg and HBcAg levels were confirmed immunohistochemically. Interferon alpha (IFN-α), interleukin 6 (IL-6), and type I interferon beta (IFN-β) levels were determined using enzyme-linked immunosorbent assay kits. p-p65, p-interferon regulatory factor (IRF) 3, and p-IRF7 expression levels were examined using western blot. The interaction of NLRX1 and retinoic acid-inducible gene (RIG)-1/mitochondrial antiviral signaling (MAVS) protein was confirmed by coimmunoprecipitation. The interaction of NLRX1 with IFN-α, IL-6, or IFN-β was analyzed by dual luciferase reporter gene assay. The levels of HBV RNA, HBsAg, and HBcAg in infected cells transfected with the WT NLRX1 or MT NLRX1 expression plasmid were higher than those in the untransfected control group; and these levels were lower in the cells transfected with MT NLRX1 than in those transfected with WT NLRX1. The levels of IFN-α, IFN-β, IL-6, p-p65, p-IRF3, and p-IRF7 were lower in cells transfected with WT NLRX1 or MT NLRX1 than in control cells. The levels of IFN-β, p-p65, p-IRF3, and p-IRF7 were higher in cells transfected with MT NLRX1 than in those transfected with WT NLRX1. Moreover, NLRX1 competitively inhibited RIG1 binding to MAVS, but the mutation in MT NLRX1 reduced this inhibitory effect. In addition, NLRX1 decreased the promoter activity of IFN-α, IFN-β, and IL-6. Our findings revealed that NLRX1 is a regulatory factor that inhibits the anti-HBV ability of hepatocytes and that the mutation p.Arg707Cys in NLRX1 suppresses HBV infection and activates the IFN/nuclear factor κB pathway.