Significant Increase In IL-6 Research Articles

Effect of Mirabilite and Rhubarb in Gynecological Laparoscopy

Recently, traditional Chinese medicine (TCM) nursing intervention has been proven to have advantages in the nursing of various diseases. Among these interventions, TCM external treatments are commonly employed in TCM nursing intervention. In this study, we aim to investigate the clinical efficacy of the external application of mirabilite and rhubarb in the perioperative nursing of gynecological laparoscopic surgery. This study included a total of 92 patients who underwent gynecological laparoscopic surgery from January 2022 to January 2023 as the study objects. They were randomly assigned into two groups, namely the conventional (Con) group (n = 46) and the TCM group (n = 46). The Con group received routine perioperative nursing care for laparoscopy, while the TCM group received topical application of rhubarb and mirabilite in conjunction with routine nursing care. We found that the combination of routine nursing and external treatment with mirabilite and rhubarb significantly reduces the ambulation time, gastrointestinal function recovery time, first defecation time, and length of hospital stay for patients undergoing gynecological laparoscopic surgery (P < 0.05). The external application of mirabilite and rhubarb effectively alleviates postoperative pain in patients (P <0.05). Furthermore, there was a significant increase in IL-6 and IL-17 levels after surgery in both groups (P <0.05); However, after receiving external treatment, patients experienced relief from their inflammatory state to some extent (P <0.05). These findings demonstrate that the perioperative nursing method involving the external application of mirabilite and rhubarb can enhance recovery in patients with gynecological diseases after laparoscopic surgery.

The Impact of NO2 on Epithelial Barrier Integrity of a Primary Cell-Based Air-Liquid Interface Model of the Nasal Respiratory Epithelium.

Nitrogen dioxide (NO2) is a pervasive gaseous air pollutant with well-documented hazardous effects on health, necessitating precise toxicological characterization. While prior research has primarily focused on lower airway structures, the upper airways, serving as the first line of defense against airborne substances, remain understudied. This study aimed to investigate the functional effects of NO2 exposure alone or in combination with hypoxia as a secondary stimulus on nasal epithelium and elucidate its molecular mechanisms because hypoxia is considered a pathophysiological factor in the onset and persistence of chronic rhinosinusitis, a disease of the upper airways. Air-liquid interface cell cultures derived from primary nasal mucosa cells were utilized as an invitro model, offering a high invitro-in vivo correlation. Our findings demonstrate that NO2 exposure induces malfunction of the epithelial barrier, as evidenced by decreased transepithelial electrical resistance and increased fluorescein isothiocyanate (FITC)-dextran permeability. mRNA expression analysis revealed a significant increase in IL-6 and IL-8 expressions following NO2. Reduced mRNA expression of the tight junction component occludin was identified as a structural correlate of the damaged epithelial barrier. Notably, hypoxic conditions alone did not alter epithelial barrier integrity. These findings provide information on the harmful effects of NO2 exposure on the human nasal epithelium, including compromised barrier integrity and induction of inflammatory responses. Overall, this study contributes to our understanding of pathophysiological mechanisms underlying also upper airway respiratory diseases associated with air pollution exposure and emphasizes the importance of mitigating NO2 emissions to safeguard respiratory health.

Different levels of lipids, Hb1Ac and cytokines among patients with coronary artery disease

BackgroundDifferent risk factors are responsible for the occurrence of coronary artery disease (CAD). Among these, the main factors are dyslipidemia, dysglycaemia, and endothelial inflammation. The aim of the study was to analyze the levels of lipids, glucose, and cytokine in patients with different coronary heart diseases. MethodsA total of 2147 patients diagnosed with coronary atherosclerosis, stable angina, unstable angina, acute non-ST-segment elevation infarction (NSTEMI) and acute ST-segment-elevation myocardial infarction (STEMI) at the Cardiovascular Center of Beijing Tongren Hospital from February 2022 to April 2023. The data were gathered from the medical record system.Nonparametric Wilcoxon test was used for statistical analysis of continuous variables, and chi-square test was used for statistical analysis of categorical variables among multiple groups. ResultsCompared with coronary atherosclerosis group, acute myocardial infarction group showed a significant increase in IL-6 level (p < 0.001). Compared with stable angina group, acute myocardial infarction group showed a significant increase in IL-6 and decrease in INF-γlevels (p < 0.001). Compared with unstable angina group, acute myocardial infarction group showed a significant increase in IL-6 level and decrease in IL-17, as well as INF-γlevels (p < 0.001). Compared with NSTEMI group, the proportion of younger, males, glycemic-lowering drugs, as well as the levels of TC, LDL-C in STEMI group increased significantly, while the proportion of hypertension, IFG/IGT/DM, hyperlipidemia and Hb1Ac level decreased significantly. STEMI group showed a significant increase in IL-2 and IL-6 levels (p < 0.05). ConclusionsThe levels of lipids, Hb1Ac, IL-2 and IL-6 were varying in patients with different stages of coronary heart diseases.The data would contribute to a deeper understanding of the roles of lipids, glucose, and inflammation in the occurrence and development of CAD.

Systemic profile of pro-inflammatory and anti-inflammatory cytokines and its changes in patients with cataract after surgery

Background. Due to its high prevalence and morbidity, cataract is an urgent medical and social problem. In recent years, immune inflammation, in particular the immune regulation of dystrophic processes, has been of great importance in the pathogenesis of eye diseases. Immunological disorders play a crucial role in the development of age-related eye diseases (cataract, corneal dystrophy, glaucoma, age-related macular degeneration). The effect of pro-inflammatory and anti-inflammatory cytokines on the development of age-related cataract remains understudied, as well at their role in predicting the course of the postoperative period after extraction of age-related cataract has not been fully stu­died, which determines the relevance of the study. The objective: to assess the state of cytokine profile in patients with age-related cataract by determining the content of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins in blood serum before and after surgical treatment of cataract. Materials and methods. The level of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory cytokines (IL-4, IL-10) was studied before and after surgical treatment in 28 patients with age-related cataract (56 eyes), 8 men and 20 women aged 42 to 82 years. The average age of the patients was 71.79 ± 1.90 years. Serum content of cytokines was determined by the enzyme-linked immunosorbent assay using test systems Vector-Best-Ukraine. Results. There was no excess of IL-1β and IL-6 reference values in the blood serum of patients with age-related cataract prior to surgical treatment. Analysis of the pro-inflammatory IL-6 in these patients depending on sex revealed a significant increase in its level by 1.3 times in men and a significant decrease by 1.1 times in women compared to its average content (p &lt; 0.06 and p &lt; 0.01, respectively). The level of anti-inflammatory IL-4 and IL-10 in the blood serum of the examined patients was within the reference values. When studying the content of pro-inflammatory and anti-inflammatory interleukins in serum depending on sex and age in patients with age-related cataract aged 75 years and older, there was a statistically significant increase in IL-6 and IL-10. In this age group, the level of IL-6 was 1.4 times higher in men compared to women, and IL-10 was 1.8 times higher in women than in men. In patients with age-related cataract after surgical treatment, serum content of pro-inflammatory IL-1β, IL-6 and anti-inflammatory IL-4, IL-10 was higher than levels before surgery. The highest levels of IL-1β, IL-6 were in patients with postoperative corneal edema. Serum content of IL-6 in patients with postoperative corneal edema was higher compared to that of IL-1β. Levels of IL-4, IL-10 were higher in patients with postoperative corneal edema, IL-10 in these patients prevailed over IL-4. Conclusions. In patients with age-rela­ted cataract, the content of pro-inflammatory and anti-inflammatory cytokines in the blood serum corresponds to reference values and has no signi­ficant differences from the control group. However, determination of the cytokine profile in people with age-related cataract revealed a violation of the systemic immunological status depending on age and gender. According to our results, patients with age-related cataract over 75 years of age had a significant increase in the level of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 in blood serum. In this age group, IL-6 was higher in men and IL-10 was higher in women. We also noted the absence of significant differences in the content of IL-1β, which may indicate a more specific value of IL-6 levels for the development of cataract. In patients with age-related cataract after surgical treatment, serum levels of pro-inflammatory IL-1β, IL-6 and anti-inflammatory IL-4, IL-10 were higher than preoperative ones. The highest levels of IL-1β, IL-6 were in the blood serum of patients with postope­rative corneal edema, and a decrease in the level of IL-4, IL-10 was also noted in cases of corneal edema. Serum content of IL-6 in patients with postoperative corneal edema was higher than that of IL-1β, and IL-10 prevailed over IL-4 levels.

Nrf-2/HO-1 activation protects against oxidative stress and inflammation induced by metal welding fume UFPs in 16HBE cells

As one of the main occupational hazards, welding fumes can cause oxidative damage and induce series of diseases, such as COPD or asthma. To clarify the effects of the metal fume ultrafine particulates (MF-UFPs) of welding fumes on oxidative damage, UFPs were collected by melt inert gas (MIG) and manual metal arc (MMA) welding, and the composition was confirmed. Human bronchial epithelial 16HBE cells were treated with 0–1000 µg/cm2 MF-UFPs to analyse the cytotoxicity, oxidative stress and cytokines. The protein and mRNA expression of Keap1-Nrf-2/antioxidant response elements (AREs) signalling pathway components were also analysed. After 4 h of treatment, the cell viability decreased 25% after 33.85 and 32.81 µg/cm2 MIG/MMA-UFPs treated. The intracellular ATP concentrations were also decreased significantly, while LDH leakage was increased. The decreased mitochondrial membrane potential and increased ROS suggested the occurrence of oxidative damage, and the results of proteome profiling arrays also showed a significant increase in IL-6 and IL-8. The expression of AREs which related to antioxidant and anti-inflammatory were also increased. These results indicate that the MF-UFPs can cause oxidative stress in 16HBE cells and activate the Nrf-2/ARE signalling pathway to against oxidative damage.

Pro-inflammatory cytokines gene expression in liver and kidneys of rats exposed to a sub-lethal dose of Bitis arietans snake venom.

Bitis arietans (Puff adder) is a poisonous snake and its bite causes pain, edema, blistering, tissue damage and neutrophilia. There are limited studies on inflammatory process involved in Bitis arietans envenomation. We therefore investigated the role of proinflammatory cytokines in Bitis arietans venom (BAV)-induced liver and kidney toxicities in rats. Adult male Sprague Dawley rats were treated with BAV (0.5 mg/kg) and were sacrificed after specific time intervals (2 h, 24 h, 1 week). Blood samples were collected for liver and renal function tests and tissues were collected for histopathology and gene expression analysis of IL-1β, IL-6, and TNF-α in liver and kidneys. There was no significant difference in serum ALT activities among different treatment groups. Serum AST was significantly increased at 24 h following BAV injection. In both organs, injection of BAV resulted in mild inflammatory cell infiltration at 2 h post-dosing which normalized after 1 week. In liver, there was a significant increase in IL-1β expression in BAV-treated rats at 2 and 24 h post-dosing that reduced after one week. Significant increases in IL-6 and TNF-α were observed at 24 h and 1 week after BAV exposure. In kidneys, there were significant increases in IL-1β and TNF-α expression at 24 h that subsided after 1 week. In conclusion, a single sub-lethal dose of BAV caused an acute phase inflammation in liver and kidneys. It is most probable that a higher dose of BAV may result in greater and irreversible damage to these organs.

298 Botanicals reduce osteoarthritic-like inflammation influencing the endocannabinoid system in vitro

Abstract Osteoarthritis (OA) is a prevalent joint disease in dogs. Botanicals (BOT) interacting with the endocannabinoid system (ECS) can reduce pain, inflammation, and other OA-related processes, and could become potential treatments for pets. This study investigates various BOT in vitro for their potential to reduce OA-like inflammation, oxidative stress, and apoptosis, and influence the expression of ECS enzymes or receptors. Capsicum oleoresin (10% capsaicinoids) at 100 ppm, cinnamaldehyde at 5 ppm, turmeric extract (95% curcuminoids) at 10 ppm, and eugenol at 10 ppm were selected for their documented ability to interact with the ECS and used as treatments. The efficacy of these BOT was assessed by pre-treating human chondrosarcoma cells (SW1353 - ATCC HTB-94) with BOT for 2 h before exposure to interleukin (IL)1β and tumor necrosis factor (TNF) α for 24 h. Following the challenge, the cells and supernatants were collected. Then, qPCR on selected markers and IL8 quantification with ELISA were conducted. Additionally, to assess antioxidant and anti-apoptotic capabilities, BOT-treated cells were exposed to menadione for 1 h to measure reactive oxygen species (ROS) and for 6 h to induce apoptosis and evaluate chondrocyte viability. Data were analyzed using one-way ANOVA with Tukey’s multiple comparisons (n = 3; P &amp;lt; 0.05) and reported in this work compared against the positive control. Under inflammatory conditions, SW1353 cells exhibited a significant increase in IL6 (234-fold; P = 0.0333) and IL8 (4,500-fold; P = 0.0395) expression, and MMP1 (13-fold, P = 0.0052), MMP3 (40-fold; P = 0.0474), and MMP13 (26-fold; P = 0.0260) expression. Among the different BOTs, only cinnamaldehyde effectively countered IL6 and IL8 upregulation, reducing their expression to 0 for IL6 and by 4,400-fold for IL8 (P = 0.0086). Additionally, it reduced MMP3 by 40-fold (P = 0.0242) and MMP13 by 24-fold (P = 0.0275), while eugenol significantly reduced MMP3 by 36-fold (P = 0.0250). Only cinnamaldehyde significantly decreased IL8 secretion by 86% (P &amp;lt; 0.0001), and all tested botanicals reduced chondrocyte apoptosis (P &amp;lt; 0.0001). Eugenol and turmeric extract exhibited significant antioxidant effects, reducing ROS levels by 70% compared with the positive control (P &amp;lt; 0.05). Concerning ECS response to the inflammatory challenge, MAGL levels increased by 4.2-fold (P = 0.0253), with cinnamaldehyde significantly reducing its mRNA expression by 4-fold (P = 0.0078). PPAR-γ expression showed a numerical decrease of 0.7-fold under inflammatory conditions, but cinnamaldehyde and capsicum oleoresin upregulated its mRNA expression by 2.3-fold (P = 0.0162) and 1.3-fold (P = 0.0006), respectively. Cinnamaldehyde also reduced DAGLα expression by 0.3-fold (P = 0.0079), and upregulated CBR2 and NRF2 mRNA expression by 7-fold (P &amp;lt; 0.0001) and 1.6-fold (P = 0.0295) respectively, while other botanicals had no effects. In conclusion, the tested BOTs displayed promising properties to mitigate OA in vitro, with cinnamaldehyde proving to be the most promising one. These findings suggest the potential of BOT active on ECS as a novel treatment for canine OA, prompting further in vivo research for comprehensive characterization.

Effect of simultaneous application of adenosine A1 receptor agonist and A2A receptor antagonist on memory, inflammatory factors, and PSD-95 in lipopolysaccharide-induced memory impairment

The potential role of adenosine, a natural neuroprotective agent, and its receptors in the pathogenesis of Alzheimer's disease has been proposed. The present study aims to examine the effect of administering both an A1 receptor agonist and an A2A adenosine receptor antagonist simultaneously on memory, inflammatory factors, and PSD-95 in an LPS-induced Alzheimer's disease model in rats. Fifty-six male Wistar rats were randomly divided into seven groups: Saline, LPS, Saline + Vehicle, LPS + Vehicle, LPS + SCH58261 (A2A receptor antagonist), LPS + CPA (A1 receptor agonist), LPS + SCH58261+CPA. LPS (3 mg/kg/ip) was used to cause memory impairment. Treatment was performed by intraventricular injection of CPA at a dose of 700 μg and SCH-58261 at 40 μg for ten days. Passive avoidance and Y-maze tests were performed to examine animals’ memories. IL-10, TNF-α, and PSD-95 levels were measured in the brain using ELISA and western blot, respectively. Compared to the groups receiving each medication separately, the simultaneous administration of CPA and SCH58261 improved memory (P<0.05). Additionally, compared to the single medication groups, there was a significant increase in IL-10, PSD-95, and a significant decrease in TNF-α in the brain tissue (P<0.05). These findings suggest that the activation of A1 receptors along with A2A receptor inhibition could be a potential therapeutic strategy for Alzheimer's disease. These findings suggest that A1 receptor activation combined with A2A receptor inhibition may be a promising therapeutic approach for Alzheimer's disease.

Investigation of the effect of macrophage and epithelial cell interaction in the progression of different subtypes of breast cancer.

10 Background: In the realm of tumor progression, the immunosuppressive role of macrophages has been well-established. However, a significant lacuna persists concerning the mechanisms through which epithelial cells regulate macrophages. Furthermore, the precise manner in which macrophages modulate breast cancer cells remains unclear. Hence, the primary objective of the current investigation is to delve into the influence of macrophages on the progression of distinct subtypes of breast cancer. Methods: Human monocyte cell-derived macrophages (M0) were cultivated in the presence of conditioned media (CM) from various subtypes of breast cancer cells. Conversely, human luminal breast cancer cell line T47D, and basal cell line MDA MB 231 were cultured in the presence of CM from macrophages. Results: When macrophages were incubated with CM of T47D, they exhibited a spindle-shaped morphology with pseudopodia. Conversely, exposure to CM of MDA MB 231 induced macrophages to adopt a foamy, round shape with numerous filopodia. Flow cytometry analysis revealed that T47D-CM promoted a higher proportion of CD80+ cells, while MDA MB 231-CM led to an increase in both CD206+ and CD80+ cells. Moreover, both T47D and MDA MB 231-CM escalated the production of various cytokines including IL-1β, IL-2, IL-4, IL-5, IL-7, IL-12(p70), IL-13, IL-17, G-CSF, IFN-γ, and MIP-1β. Intriguingly, MDA MB 231-CM induced a significant increase in IL-6, GM-CSF, and TNF-α. Subsequent cultivation of cancer cells in the presence of macrophage-CM resulted in a marked proliferation of MDA MB 231 cells, while T47D cell proliferation decreased significantly. Correspondingly, there was a notable increase in apoptosis among T47D cells. Scratch wound healing assays revealed heightened migration of MDA MB 231 cells following treatment with macrophage-CM, whereas there was negligible alteration in T47D cell migration. Proteomic analysis unveiled dysregulation of 247 and 596 proteins in MDA MB 231 and T47D cells, respectively. Particularly noteworthy were three proteins—MDHM, H1.5, and LEG8—abundant in MDA MB 231 cells, yet scarce in T47D cells. These proteins have been implicated in promoting tumor growth across various cancer types. Conclusions: This study first time elucidates subtype specific role of macrophage in breast tumour. In triple-negative breast cancer, infiltrating macrophages induce an immunosuppressive effect, altering cytokine expression and fostering the expression of tumor-promoting factors in epithelial cells, thereby facilitating cellular proliferation and metastasis. Conversely, in luminal breast cancer, infiltrating macrophages exhibit a predominantly pro-inflammatory profile, resulting in minimal tumor-promoting effects. Key Words: Breast Cancer, Macrophage polarization, Conditioned Media, Cytokines, Proteomics. Acknowledgements, DBT – Govt of India, NIBMG, Kalyani.

The evaluation of cytokines in predicting the organ injury of critically pediatric patients: a retrospective study.

The current early warning model for organ damage in critically ill patients has certain limitations. Based on the pathological mechanism, the establishment of an early warning system for organ damage in critically ill children using cytokines profile has not been explored. The aim of this study is to explore the predicting value of cytokines in critically ill patients. There were 200 critically pediatric patients and 49 general patients between August 22, 2018 and April 28, 2023 from Children's Hospital of Soochow University enrolled in this study. The clinical information was retrospectively collected and analyzed. The cytokine profiles of these patients were detected by flow cytometry. Receiver operating characteristic (ROC) curves were plotted to determine the association between the cytokines and organ injury. There were no statistically significant differences in gender, age and underlying disease between critically ill patients and general patients. The interleukin (IL)-6 (P<0.001), IL-10 (P<0.001), IL-17A (P=0.001), tumor necrosis factor-α (TNF-α) (P=0.02) and interferon-γ (IFN-γ) (P=0.02) level in the critically patients were significantly higher than those in the general patients. The results showed that the incidence of acute gastrointestinal injury (AGI) and acute kidney injury (AKI) in critically ill patients was 39% and 23.5%, respectively. Moreover, there were 4% and 3.5% patients with the occurrence of cardiac arrest and acute live injury. The IFN-γ level was increased in these patients with acute liver injury compared to those without these organ injuries, but reduced in the patients with AGI compared to those without. The patients with AKI showed a significant increase in IL-10 in contrast to those without. The IL-2, IL-4, IL-6, IL-10 and IL-17A were higher in patients with acute liver failure (ALF), but TNF-α was reduced, compared to those without. The IL-2, IL-4, IL-6 and IL-10 were significantly increased in the patients with cardiac arrest compared to those without. When IL-10 was higher than 279.45 pg/mL, the sensitivity and specificity for predicting cardiac arrest were 0.875 and 0.927, respectively. While the sensitivity and specificity of IL-6 (more than 1,425.6 pg/mL) were 0.625 and 0.844, respectively. However, no synergistic effect of IL-6 and IL-10 was observed for predicting cardiac arrest. Additionally, the IL-17A (more than 21.6 pg/mL) was a good predictor for the incidence of ALF (sensitivity =0.714, specificity =0.876). The cytokines profile was different between critically ill patients with organ injury and those without organ injury. The IL-6 and IL-10 levels were good predictors for cardiac arrest in critically ill patients. Additionally, higher IL-17A predicted the incidence of ALF of the critically ill patients.

High-dimensional longitudinal immune profiling uncovers a dual role of the CXCL9/CXCR3, CXCL13/CXCR5, and CCL11/CCL3 axis in the coupling of immune-related adverse events to immune checkpoint inhibitor response.

2512 Background: Additional characterization is required to understand the immune network signatures and immunophenotypes that link immune-related adverse events (irAEs) to immune checkpoint inhibitor (ICI) therapy responses in cancer patients. Methods: A comprehensive immune profiling analysis was conducted on whole blood and peripheral blood mononuclear cells (PBMC) from 165 oncology patients with various irAEs, including colitis (n=64), myocarditis (n=19), pneumonitis (n=25), arthritis (n=24), and cytokine release syndrome CRS (n=33), and compared to a cohort of 219 cancer patients prior to ICI treatment. Results: Following ICI therapy on cycle 2 day 1 (C2D1), we observed significant increases in IL-6, CCL2, CXCL9, CXCL10, and CXCL13 levels preceding irAEs. CXCL9 was specifically upregulated during the development of colitis, arthritis, CRS, and myocarditis, while CXCL13 increased only in CRS, and CCL3 only in myocarditis and CRS, with no CCL11 upregulation in any irAE. High levels of CXCL9, high CCL11 and low CXCL13 strongly correlated with improved oncologic outcomes in different irAEs. Compared to other cluster, in the high CXCL9 cluster, 5-year overall survival (OS) was significantly improved (HR = 10.26 [95% CI, 1.27-82.82], p = 0.029) in colitis (n=20), in CRS (n=21) (HR = 6.45 [95% CI, 1.60-25.99], p = 0.009), and in arthritis. In the high CCL11 cluster, 5-year OS was significantly improved in pneumonitis (n=15), (HR = 4.04 [95% CI, 1.05-15.46]). Conversely, in myocarditis, the high CXCL13 cluster (n=9) was associated with decreased 2-year OS (HR = 6.05 [95% CI, 1.03-35.48], p = 0.046). It is important to note that the CXCL9-driven immunophenotypes were characterized by low IL-6. Notable observations include CD38 upregulation and large-scale activation of CD8 memory subsets during ICI therapy, concomitant with increased circulation of immature neutrophils at the onset of irAEs diagnosis. This event may increase the migration of TCRγδ, NK, DC, and CD8 cells to tumor sites through CXCR3/CXCL9 interactions. Conclusions: This study unravels intricate connections between immune activation and tumor response. CXCL9, CCL11, and CXCL13 emerge as pivotal biomarkers bridging the gap between ICI therapy effectiveness and distinct irAEs-associated immunophenotypes.

Co-administration of probiotics and vitamin D reduced disease severity and complications in patients with Parkinson's disease: a randomized controlled clinical trial.

Probiotics have beneficial effects on the nervous system by modulating the gut-brain axis. Additionally, vitamin D supplementation presents a potential way for ameliorating neuropsychological disorders, particularly in regions with a high prevalence of vitamin D deficiency. The current clinical trial aimed to investigate the role of co-administered supplementation of probiotics and Vitamin D on the different inflammatory aspects of patients with Parkinson's disease. Forty-six patients with PD were recruited From the Functional Neurosurgery Research Center, Tehran, Iran. These patients were randomly allocated to one of the two treatment groups: Group A, who received probiotic/vitamin D supplements (n = 23), and Group B who received placebo capsules (n = 23) for 12 weeks. As primary outcomes, Interferon-Gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-6, IL-10, Tumor Necrosis Factor-Alpha (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in serum were evaluated at the baseline and the end of the trial. Moreover, Additional questionnaire-based factors including gastrointestinal symptom rating scale (GSRS), Beck Anxiety Inventory (BAI), and Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. Our findings demonstrated that the consumption of probiotic/vitamin D supplements leads to a significant decrease in IL-1β, INF-γ, IL-6, and MDA levels, while showing a significant increase in IL-10 and TAC levels compared to the placebo group (P < 0.05). Additionally, it leads to a significant decrease in the disease severity, anxiety, and gastrointestinal problems in PD patients in comparison to the placebo group (P < 0.05). Given the acknowledged role of inflammation in the pathogenesis of Parkinson's disease on one hand, and the recognized anti-inflammatory and antioxidant effects associated with probiotics and vitamin D on the other hand, the concurrent administration of probiotics and vitamin D supplements emerges as a promising and potentially effective treatment option for individuals with PD.

Gender disparities in lymphocyte counts and cytokine expression in COVID-19

Background: This study seeks to assess gender differences in the severity of COVID-19 infection, which have been noted in different regions during the early stages of the pandemic. Methods: A cross-sectional study conducted at Baquba Teaching Hospital in Diyala, Iraq, from October 1st to December 31st, 2020, included 132 confirmed COVID-19 patients. These patients underwent a comprehensive set of routine laboratory tests, including complete blood count, blood biochemistry, and D-dimer assessment. Statistical analysis was carried out using SPSS-20, with significance set at p &lt; 0.05. Results: The study included patients with a mean age of 45.61 (±11.32) years, predominantly male (63.0%), residing in urban areas (57.6%), and presenting with comorbidities (78.8%). All patients exhibited positive results on CT scans (100%) and CRP tests (100%). However, PCR testing confirmed COVID-19 infection in 87.2% of cases, with 12.8% testing negative. Among males, there was a significant increase in IL-6 and IL-10 levels (42.57 ± 7.64 pg/ml and 255.27 ± 21.03 pg/ml) compared to females (16.43 ± 4.19 pg/ml and 187.48 ± 20.35 pg/ml), with p-values &lt;0.001 and 0.003, respectively. Conversely, there was no significant difference in IFN-ɣ levels between males (165.73 ± 16.54 pg/ml) and females (176.12 ± 17.10 pg/ml), with a p-value of 0.105. However, lymphocyte levels were significantly lower in males (4.79 ± 0.85%) compared to females (14.01 ± 1.36%), with a p-value &lt;0.001. Conclusion: Overall, COVID-19 affects males more severely than females, with males showing weaker immune responses and higher levels of inflammatory cytokines like IL-6 and IL-10. While IFN-ɣ levels do not differ significantly between genders, males have lower lymphocyte counts compared to females.

THE ROLE OF IL6 GENE POLYMORPHISM –174C/G IN THE DEVELOPMENT OF RECURRENT BRONCHIAL OBSTRUCTION IN CHILDREN OF EARLY SCHOOL AGE

The purpose of our work was to analyze the polymorphism of the IL6 gene –174C/G in the development of recurrent bronchitis in children of the Uzbek population of preschool age. Material and methods. To achieve this goal, 73 cases of the disease were analyzed, of which group 1 included children with acute obstructive bronchitis (AOB), group 2 - with recurrent bronchial obstruction (RBO) aged 7 to 11 years. Determination of IL-6 and total IgE in blood serum was carried out by enzyme-linked immunosorbent assay using a commercial kit of enzyme-linked immunosorbents. Total genomic DNA was isolated using the DNA-Express kit (Litekh). Single nucleotide polymorphism of the IL-6 gene 174G/C was determined by PCR. Statistical processing of the obtained data was carried out using Microsoft Excel 2013. Differences were considered statistically significant at p &lt; 0.05. Results. A comparative analysis of IL6 and total IgE in AOB and RBO showed a significant increase in IL-6 and an increase in the level of IgE in RBO compared with the AOB group and healthy children. A study of the IL6 –174C/G gene polymorphism showed that the G/G mutacin genotype was observed significantly more often in the group of patients with RBO than in the healthy group. Conclusion: It follows that the main allele G is associated with an increased level of IL-6 expression and is a prognostic factor for the development of RBO in children. The obtained clinical, genetic and immunological results of the study allow us to predict RBR in children.

Abstract 1415: Reduction in photoimmunotherapy-induced edema with COX-2 inhibition: Combatting clinically relevant adverse events without compromising efficacy

Abstract ASP-1929 photoimmunotherapy (PIT), an investigational drug-device combination, consists of an epithelial growth factor receptor (EGFR)-targeting drug, cetuximab, conjugated to a light-activatable dye, IRDye® 700DX, and a laser light. Localized illumination results in rapid and selective tumor necrosis in the preclinical setting, and early clinical studies demonstrate a manageable safety profile in patients with head and neck squamous cell carcinoma. In the ongoing clinical trials, however, edema is a commonly reported adverse event and laryngeal edema, requiring prophylactic tracheostomy, has been noted in some patients. Thus, a critical need exists to provide clinicians with tools to manage ASP-1929 PIT-associated edema to ensure optimal patient outcome. To evaluate edema following cancer-targeted PIT, we developed a mouse tumor model and used it to characterize the mechanism of edema development and evaluate various methods for edema reduction. Briefly, cohorts of mice bearing syngeneic LL/2 tumors engineered to express Ephrin A2 (EphA2) were administered an anti-EphA2 antibody conjugated to IR700 (conjugate) or saline control. Light was applied 24h following administration and edema was measured by caliper. In control mice, light alone did not generate edema; however, mice treated with conjugate plus light showed a light-dose dependent increase in edema volume which peaked at 6h post light delivery. We next evaluated a series of inflammatory cytokines and immune cell populations in the blood and tumor region at the onset (2h), peak (6h), and resolution (24h) of PIT-induced edema. We found a striking increase in neutrophils (500-fold greater than control mice, n=10, p&amp;lt;0.0001) in the blood at the peak of edema formation coinciding with a significant increase in IL-6 (n=5, p&amp;lt;0.001) and IL-10 (n=5, p&amp;lt;0.05), indicating the onset of a heightened inflammatory response. To combat the edema formation, we next evaluated the effect of various anti-inflammatory drugs commonly used in the clinical setting. Cohorts of mice were administered conjugate plus light in the presence or absence of steroids or the selective COX-2 inhibitor meloxicam. Results show there is no reduction in edema by steroids regardless of timing of administration. Conversely, the addition of meloxicam resulted in a significant reduction in edema at all time points and light doses evaluated: 40-50% reduction at both 2h and 6h post-PIT when administered prophylactically and 25% reduction at 6h post-PIT when administered post-light (all settings, n=10, p&amp;lt;0.0001). Importantly, we found the reduction in edema with meloxicam was not associated with a loss of therapeutic benefit based on measurement of tumor growth. In conclusion, the use of COX-2 inhibitors may be directly translated to the clinic for the benefit of patients receiving ASP-1929 PIT and should undergo further evaluation. Citation Format: Gina Ma, Myra Gordon, Jason Lapetoda, Abram Lozano, Christopher M. Amantea, Takuya Osada, Amy H. Thorne. Reduction in photoimmunotherapy-induced edema with COX-2 inhibition: Combatting clinically relevant adverse events without compromising efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1415.

Immuno-Enhancing Effects of Galium aparine L. in Cyclophosphamide-Induced Immunosuppressed Animal Models.

This study investigates the immunomodulatory potential of Galium aparine L. (GAE) in immunodeficient animals. In this study, animals were categorized into five groups: the normal group, CYP group (cyclophosphamide intraperitoneal injection), GA5 group (cyclophosphamide + 5 μg GAE), GA50 group (cyclophosphamide + 50 μg GAE), and GA500 group (cyclophosphamide + 500 μg GAE). The CYP group exhibited significantly reduced spleen weights compared to the normal group, while the groups obtaining GAE displayed a dose-dependent increase in spleen weight. Furthermore, the GAE demonstrated dose-dependent enhancement of splenocyte proliferating activity, with significant increases observed in both LPS and ConA-induced assays. NK cell activity significantly increased in the GA50 and GA500 groups compared to the CYP group. Cytokine analysis revealed a significant increase in IL-6, TNF-α, and IFN-γ levels in ConA-induced splenocytes treated with GAE. Gene expression analysis identified 2434 DEG genes in the extract groups. Notable genes, such as Entpd1, Pgf, Thdb, Syt7, Sqor, and Rsc1al, displayed substantial differences in individual gene expression levels, suggesting their potential as target genes for immune enhancement. In conclusion, Galium aparine L. extract exhibits immunomodulatory properties. The observed gene expression changes further support the potential of Galium aparine L. extract as a natural agent for immune augmentation.

The priority of mesenchymal stem cells treated with melatonin in ameliorating thyroid impairment induced by amiodarone. Thorough look on the apoptotic pathway

Amiodarone treatment has been associated with thyroid alterations. This work was planned to consider therapeutic outcome of MSCs versus MSCs treated with melatonin in minimizing amiodarone –induced deviations in thyroid.We handed-down 50 male Wistar rats, then distributed them into 5 groups; I, II, III, IV, V; control, sham control, amiodarone treated, amiodarone and MSCs treated, and amiodarone, MSCs and melatonin treated groups respectively. Light microscopic examination; levels of T3, T4 and TSH, Oxidative/antioxidative tissue markers, immune-histochemical staining (Bcl2, BAX, iNOS) and real time PCR (IL-6 and VEGF and Caspase 3) were done. Results of group III showed degenerated follicles, decreased follicular cell count and diminished colloid. Some of the follicles were dilated with signs of inflammatory response and apoptosis. Increased collagen deposition in group III was marked. The positive immune-reactive cells of Bcl-2 was decreased and that of BAX and iNOS was increased, also T3 and T4 levels were significantly decreased, but TSH was significantly increased in group III comparing it to the group I. There were highly significant diminution in both SOD and GPx and upsurge in MDA intensities in groups III, IV when correlated to the control. In group IV and V the aforementioned values were restored. The PCR results showed significant increase in IL-6 and VEGF and Caspase 3 in group III compared to the control one, whereas, their values in groups IV and V were reestablished. It is concluded that stem cells can to a great extent ameliorate the thyroid damage induced by amiodarone.But, Adding melatonin to the stem cells culture was found to have auxiliary beneficial effect in the improving the thyroid structure and function.

The CSF1-CSF1R pathway in the trigeminal ganglion mediates trigeminal neuralgia via inflammatory responses in mice.

Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.

Salmon louse labial gland enzymes: implications for host settlement and immune modulation.

Salmon louse (Lepeophtheirus salmonis) is a skin- and blood-feeding ectoparasite, infesting salmonids. While feeding, labial gland proteins from the salmon louse may be deposited on the Atlantic salmon (Salmo salar) skin. Previously characterized labial gland proteins are involved in anti-coagulation and may contribute to inhibiting Atlantic salmon from mounting a sufficient immune response against the ectoparasite. As labial gland proteins seem to be important in the host-parasite interaction, we have, therefore, identified and characterized ten enzymes localized to the labial gland. They are a large group of astacins named L. salmonis labial gland astacin 1-8 (LsLGA 1-8), one serine protease named L. salmonis labial gland serine protease 1 (LsLGSP1), and one apyrase named L. salmonis labial gland apyrase 1 (LsLGAp1). Protein domain predictions showed that LsLGA proteins all have N-terminal ShK domains, which may bind to potassium channels targeting the astacins to its substrate. LsLGA1 and -4 are, in addition, expressed in another gland type, whose secrete also meets the host-parasite interface. This suggests that LsLGA proteins may have an anti-microbial function and may prevent secondary infections in the wounds. LsLGAp1 is predicted to hydrolyze ATP or AMP and is, thereby, suggested to have an immune dampening function. In a knockdown study targeting LsLGSP1, a significant increase in IL-8 and MMP13 at the skin infestation site was seen under LsLGSP1 knockdown salmon louse compared to the control, suggesting that LsLGSP1 may have an anti-inflammatory effect. Moreover, most of the identified labial gland proteins are expressed in mature copepodids prior to host settlement, are not regulated by starvation, and are expressed at similar or higher levels in lice infesting the salmon louse-resistant pink salmon (Oncorhynchus gorbuscha). This study, thereby, emphasizes the importance of labial gland proteins for host settlement and their immune dampening function. This work can further contribute to anti-salmon louse treatment such as vaccine development, functional feed, or gene-edited salmon louse-resistant Atlantic salmon.

Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis

BackgroundThe term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.MethodsWe infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.ResultsOne day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.ConclusionsIntraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.