Chronic Low-level Inflammation Research Articles

Nuclear Factor Kappa B p65: A Possible Biomarker for Persistent Inflammation in HIV-1 Infection?

Low-grade inflammation in people living with HIV (PWH) has become a significant contributor to the development of non-communicable diseases (NCDs) such as heart disease, stroke, and renal dysfunction. Though antiretroviral therapy (ART) has dramatically reduced mortality by limiting the emergence of opportunistic infections, it has not been successful in eliminating the remaining chronic, low-grade inflammation and activation that persists in the infected despite viral suppression and better CD4+ T cell count. Nonetheless, this relatively asymptomatic and subclinical chronic inflammation remains poorly understood and has become a major contributor to mortality in PWH. Another important component involved in this step is the Nuclear Factor kappa B (NF-κB) which is a central transcription factor in the immune system to respond to infection. Specifically, the p65/RELA subunit attaches to the HIV LTR (long terminal repeat) gene and consequently initiates the synthesis of genes related to inflammation and immune reactions. Persistent low-level chronic inflammation contributes to the pathophysiology of metabolic-inflammatory NCDs. Therefore, this review aims to assess the complex contextual function of NF-κB p65 during HIV-1 disease, particularly among individuals on ART who achieve viral suppression. As much as ART has helped to arrest the progression of the virus, immune function, and chronic inflammation have not been reversed in most PWH. It is, therefore, pertinent to know how the NF-κB p65 molecule remains involved in those with persistent immune inflammation concerns to enhance strategies on the same. This review will also discuss the possible variation in NF-κB p65 activity in particular population groups such as MSM (men who have sex with men) to acquire additional information that could potentially enhance the treatment.

Environment, Lifestyles, and Climate Change: The Many Nongenetic Contributors to The Long and Winding Road to Autoimmune Diseases.

A critical unanswered question is what is causing the increase in the prevalence of autoimmunity and autoimmune diseases around the world. Given the rapidity of change, this is likely the result of major recent alterations in our exposures to environmental risk factors for these diseases. More evidence is becoming available that the evolution of autoimmune disease, years or even decades in the making, results from multiple exposures that alter susceptible genomes and immune systems over time. Exposures during sensitive phases in key developmental or hormonal periods may set the stage for the effects of later exposures. It is likely that synergistic and additive impacts of exposure mixtures result in chronic low-level inflammation. This inflammation may eventually pass thresholds that lead to immune system activation and autoimmunity, and with further molecular and pathologic changes, the complete clinical syndrome emerges. Much work remains to be done to define the mechanisms and risk and protective factors for autoimmune conditions. However, evidence points to a variety of pollutants, xenobiotics, infections, occupational exposures, medications, smoking, psychosocial stressors, changes in diet, obesity, exercise, and sleep patterns, as well as climate change impacts of increased heat, storms, floods, wildfires, droughts, UV radiation, malnutrition, and changing infections, as possible contributors. Substantial investments in defining the role of causal factors, in whom and when their effects are most important, the necessary and sufficient gene-environment interactions, improved diagnostics and therapies, and preventive strategies are needed now to limit the many negative personal, societal, and financial impacts that will otherwise occur.

Analysis of Inflammatory Markers in Response to Induction of Reprometabolic Syndrome by a Eucaloric High Fat Diet in Normal Weight Women.

Obesity is associated with chronic low-level inflammation and is known to contribute to metabolic dysfunction and hypogonadotropic hypogonadism, which we have previously termed the 'Reprometabolic Syndrome.' To investigate potential factors involved in obesity-related reproductive endocrine dysfunction, we conducted a secondary analysis of inflammatory markers in a sample of normal weight women exposed to a one-month eucaloric high-fat diet (HFD), which, as reported earlier, induced the relative hypogonadotropic hypogonadism characteristic of Reprometabolic Syndrome. Eighteen healthy women with a BMI between 18.0-24.9kg/m2 and regular menstrual cycles participated in the study. Frequent blood sampling was performed during the early follicular phase before and after the one-month eucaloric HFD intervention (48% of calories from fat). Serum samples pooled from each participant were analyzed using immunoassay to measure levels of 30 cytokines, interleukins, and chemokines. Differences between pre- and post-HFD intervention measures were examined by one-sample t-tests. Exposure to the eucaloric HFD did not result in changes in body weight. HFD-induction of Reprometabolic Syndrome in normal weight women was associated with a significant elevation only in the anti- inflammatory cytokine IL-10 (p = 0.04). Eotaxin, IL-6 and MIP-1β also increased in response to the HFD, but not statistically significantly (p = 0.07). Results suggest that the increase in multiple inflammatory markers, typically associated with obesity, are not primary mediators of the relative hypogonadotropic hypogonadism of Reprometabolic Syndrome. Clinical Trials Registration Number: NCT02653092; Date of Registration: January 6, 2016.

The Role of PGC-1α in Aging Skin Barrier Function.

Skin provides a physical and immune barrier to protect the body from foreign substances, microbial invasion, and desiccation. Aging reduces the barrier function of skin and its rate of repair. Aged skin exhibits decreased mitochondrial function and prolonged low-level inflammation that can be seen in other organs with aging. Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), an important transcriptional coactivator, plays a central role in modulating mitochondrial function and antioxidant production. Mitochondrial function and inflammation have been linked to epidermal function, but the mechanisms are unclear. The aim of this review is to discuss the mechanisms by which PGC-1α might exert a positive effect on aged skin barrier function. Initially, we provide an overview of the function of skin under physiological and aging conditions, focusing on the epidermis. We then discuss mitochondrial function, oxidative stress, cellular senescence, and inflamm-aging, the chronic low-level inflammation observed in aging individuals. Finally, we discuss the effects of PGC-1α on mitochondrial function, as well as the regulation and role of PGC-1α in the aging epidermis.

Inflammatory biomarkers and state of the tibiofemoral joint in the osteoarthritic knee: a narrative review.

The healing process is initiated by injurious stimuli in response to cellular damage. Upon recruiting proinflammatory biomarkers to the tissue site of injury, the release of additional biomarkers occurs, including the likes of cytokines, matrix molecules, macrophages, neutrophils, and others. This influx of immune system mediators can occur for chronic periods, and though its intention is for healing the original injurious stimuli, it is also suspected of causing long term cartilage impairment following internal structure damage. The objective of this narrative review is to identify which inflammatory factors have the leading roles in the progression of osteoarthritis (OA) following knee injuries and how they fluctuate throughout the healing process, both acutely and chronically. This narrative review was performed following a computerized search of the electronic database on PubMed in May 2023. Abstracts related to the inflammatory biomarkers of the post-traumatic knee were included for review. The chronic low-level inflammation that leads to OA leads to the destruction of the cartilage extracellular matrix, which new and developing orthopedic research is still attempting to find resolve for. Some of this damage is attributed to the biomechanical alterations that occurs following injury, though with most procedures capable of joint biomechanical restoration, focus has rather been shifted toward the environment of inflammatory biomarkers. Future studies will be aiming to improve the diagnostics of OA, focusing on a consistent correlation of inflammatory biomarkers with imaging. Additionally, biochemical treatments will need to focus on validating reproducible modulation of signaling molecules, in attempts to lessen the chronic elevations of destructive biomarkers.

Exposure to Gulf war illness-related chemicals exacerbates alcohol-induced liver damage in rodents

Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war, consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on the pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB-treated mice. Male C57BL/6 mice were injected daily with vehicle or PER/PB for 10 days, followed by 4 months recovery, then treatment with PLX3397 and a chronic-plus-single-binge EtOH challenge for 10 days. PER/PB exposure resulted in the protracted increase in liver transaminases in the serum and induced chronic low-level microvesicular steatosis and inflammation in GWI vs Naïve mice up to 4 months after cessation of exposure. Furthermore, prior exposure to PER/PB also resulted in exacerbated response to EtOH-induced liver injury, with enhanced steatosis, ductular reaction and fibrosis. The enhanced EtOH-induced liver damage in GWI-mice was attenuated by strategies designed to deplete macrophages in the liver. Taken together, these data suggest that exposure to GWI-related chemicals may alter the liver’s response to subsequent ethanol exposure.

A Pilot Study to Investigate Peripheral Low-Level Chronic LPS Injection as a Model of Neutrophil Activation in the Periphery and Brain in Mice.

Lipopolysaccharide-induced (LPS) inflammation is used as model to understand the role of inflammation in brain diseases. However, no studies have assessed the ability of peripheral low-level chronic LPS to induce neutrophil activation in the periphery and brain. Subclinical levels of LPS were injected intraperitoneally into mice to investigate its impacts on neutrophil frequency and activation. Neutrophil activation, as measured by CD11b expression, was higher in LPS-injected mice compared to saline-injected mice after 4 weeks but not 8 weeks of injections. Neutrophil frequency and activation increased in the periphery 4-12 h and 4-8 h after the fourth and final injection, respectively. Increased levels of G-CSF, TNFa, IL-6, and CXCL2 were observed in the plasma along with increased neutrophil elastase, a marker of neutrophil extracellular traps, peaking 4 h following the final injection. Neutrophil activation was increased in the brain of LPS-injected mice when compared to saline-injected mice 4-8 h after the final injection. These results indicate that subclinical levels of peripheral LPS induces neutrophil activation in the periphery and brain. This model of chronic low-level systemic inflammation could be used to understand how neutrophils may act as mediators of the periphery-brain axis of inflammation with age and/or in mouse models of neurodegenerative or neuroinflammatory disease.

Effects of Exercise Intensities on Changes in Pro-/Anti-inflammatory Cytokines following 8-weeks of Aerobic Exercise Training

Inflammatory cytokines are useful biomarkers in predicting the development of metabolic and cardiovascular diseases and may be positively affected by physical activity and weight loss. Despite much interest in chronic low-level inflammation in the obese population, effects of aerobic training intensity on inflammatory cytokines remain elusive. PURPOSE: The purpose of this study was to investigate effects of 8-week aerobic exercise training at high and low intensities on changes in pro-/anti-inflammatory cytokines. Methods: Fifty three inactive obese Hispanic females (mean BMI = 34.5 kg/m2, aged 34-46 years) were divided into one of three groups: low intensity training group (LT: walking at 55% VO2max, n=16), high intensity training group (HT: running at 70% VO2max, n=18), and control group (CON: no intervention, n=19). LT and HT performed aerobic exercises three times per week at the given intensities. Exercise volume for two exercise groups was equated relative to kilograms of body weight by adjusting duration of exercise session (approximately 60 minutes for LT and 40 minutes for HT per session). Blood samples were collected before and after 8 weeks of intervention to measure levels of adiponectin, C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α). Two-way repeated measures ANOVA and Tukey post hoc tests were used for data analysis. Results: Level of adiponectin showed no significant change in any groups after 8 weeks of aerobic exercise intervention. A significant decrease in CRP was observed in the HT group only (4.12 ±.26mg/L mean±SE → 3.89±.37, P=.041), but levels of TNF-a were significantly decreased in both LT (4.57±.24pg/mL → 4.14±.31, P=.019) and HT (4.54±.25 → 4.02±.41, P=.011). No changes were observed in CON. CONCLUSIONS: Significant decreases in CRP and TNF-a were found following high intensity aerobic exercise training while low intensity training reduced TNF-a only. The greater changes of pro-inflammatory cytokines in HT indicates high intensity aerobic exercise training may be more beneficial than low intensity training. Specifically, for controlling low-grade inflammation and immune function in obese Hispanic females. This study confirmed results of previous studies suggesting that longer period of exercise training with distinct fat loss may be required to induce significant changes in adiponectin in obese adults. TAMIU university research grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SHIP1 deficiency causes inflammation-dependent retardation in skeletal growth.

Inflammation and skeletal homeostasis are closely intertwined. Inflammatory diseases are associated with local and systemic bone loss, and post-menopausal osteoporosis is linked to low-level chronic inflammation. Phosphoinositide-3-kinase signalling is a pivotal pathway modulating immune responses and controlling skeletal health. Mice deficient in Src homology 2-containing inositol phosphatase 1 (SHIP1), a negative regulator of the phosphoinositide-3-kinase pathway, develop systemic inflammation associated with low body weight, reduced bone mass, and changes in bone microarchitecture. To elucidate the specific role of the immune system in skeletal development, a genetic approach was used to characterise the contribution of SHIP1-controlled systemic inflammation to SHIP1-dependent osteoclastogenesis. Lymphocyte deletion entirely rescued the skeletal phenotype in Rag2 -/- /Il2rg -/- /SHIP1 -/- mice. Rag2 -/- /Il2rg -/- /SHIP1 -/- osteoclasts, however, displayed an intermediate transcriptomic signature between control and Rag2 +/+ /Il2rg +/+ /SHIP1 -/- osteoclasts while exhibiting aberrant in vitro development and functions similar to Rag2 +/+ /Il2rg +/+ /SHIP1 -/- osteoclasts. These data establish a cell-intrinsic role for SHIP1 in osteoclasts, with inflammation as the key driver of the skeletal phenotype in SHIP1-deficient mice. Our findings demonstrate the central role of the immune system in steering physiological skeletal development.

Associations of inflammatory cytokines and cortisol with nonmotor features of Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disease involving progressive motor abnormalities, cognitive decline, and psychiatric disturbances. Depression and cognitive difficulties are among the most impactful symptoms of HD, yet the pathogenesis of these symptoms is not fully understood. HD involves low-level chronic inflammation and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which are linked to depression and cognitive impairment in non-HD populations. However, previous research on the relationships of these pathologies with depression and cognition in HD is limited and inconsistent. Fifty-three adults with the HD gene expansion (30 premanifest and 23 manifest) completed measures of depression and cognitive functioning. Forty-eight out of 53 participants provided hair samples for quantification of cortisol, and 34 participants provided blood samples for quantification of peripheral inflammatory cytokines. We examined the associations of four cytokines (interleukin [IL]-6, IL-10, IL-1β, and tumor necrosis factor [TNF]-α) and cortisol levels with depression and cognitive scores. In unadjusted models, higher levels of plasma IL-6, IL-10, and TNF-α correlated with higher depression scores, and higher levels of IL-10 and TNF-α correlated with poorer cognitive performance. After controlling for age, sex, and body mass index, only the correlations of IL-10 with depression and cognitive performance remained significant. No correlations were evident with hair cortisol. Peripheral inflammation is associated with depression symptoms and cognitive impairment in HD. Our findings suggest that interactions between the immune and nervous systems are important in HD, and highlight the potential of chronic inflammation as a therapeutic target in early stages of HD.

Microbiota and Lipotoxicity.

Gut microbiota is an indispensable commensal partner of human superorganism. The wealth of genetic repertoire provided by these microorganisms extends host's substrate processing capability. Energy and nutrient harvesting machinery primarily depends on the proper function of these organisms. However, the dynamic composition of microbiota changes with age, lifestyle, stress factors, infections, medications, and host pathophysiological conditions. Host immune system is primarily responsible for shaping up the microbial community and sustaining the symbiotic state. This involves controlling the delicate balance between agility toward pathobionts and tolerance toward symbionts. When things go wrong with this crosstalk, dysbiosis may arise.Metabolic syndrome is a multisystemic, low-grade chronic inflammatory disease that involves dyslipidemia, glucose intolerance, insulin resistance, and central obesity. Excess caloric intake with high-sugar and high-fat diet promote high energy harvesting and lipogenesis. The secretion of adipokines accompanies lipid spillover from fat cells, which contribute to insulin resistance and the expansion of adipose tissue in ectopic sites. Proinflammatory cytokines from adipose tissue macrophages increase the extent of adipose dysfunction.The inflammatory nature of obesity and metabolic syndrome recall the connection between dysbiosis and immune dysfunction. A remarkable association exits between obesity, inflammatory bowel disease, gluten-sensitive enteropathy, and dysbiosis. These conditions compromise the gut mucosa barrier and allow lipopolysaccharide to enter circulation. Unresolved chronic inflammation caused by one condition may overlap or trigger the other(s). Experimental studies and therapeutic trials of fecal microbiota transplantation promise limited improvement in some of these conditions.Typically, metabolic syndrome is considered as a consequence of overnutrition and the vicious cycle of lipogenesis, lipid accumulation, and chronic low-level inflammation. Because of the complex nature of this disorder, it remains inconclusive whether dysbiosis is a cause or consequence of obesity and metabolic syndrome.

The Relationship between Muscle Aging, Bone Tissue and Sports Activities

Aim: This research was conducted with the aim of investigating the relationship between muscle aging, bone tissue and sports activities in 2024. Methodology: Based on the nature of the data, this research is qualitative research, in terms of the purpose of applied research, and in terms of data collection tools, it is descriptive research. Due to the fact that the current research was conducted using the descriptive method of analysis and is based on library and documentary studies, therefore, the authentic document scanning tool was used to collect the information required for the literature section of the research. To answer the research question, the phenomenological method has been used. The phenomenological method can be used for research on any aspect of natural or social reality about which people have gained an understanding. The statistical population of the current research also includes men and women 50 years and older in Mashhad. The participants of this research are 30 people, 15 men and 15 women who were selected. In this research, the researcher has used purposeful sampling. Results: The findings of this research show that the effects of heavy sports training on aging of muscle and bone tissue are combined. 8 weeks of resistance training in middle-aged women with metabolic syndrome, which is associated with low-level chronic inflammation, increases the systematic baseline amount of bone loss compared to the control group, and this indicates that heavy resistance training reduces the amount of bone loss. which has a positive effect on bone tissue. Aerobic resistance exercises for 8 months in a group of middle-aged women 30 to 68 years old had no effect on the amount of systematic rest bone loss. There are also other cytokines that affect bone tissue in different models of bone tissue. Alendronate-calcitriol has a negative relationship with the base bone of the back and a positive relationship with the concentration of parathyroid hormone. Conclusion: Myostatin, which is considered a myokine and prevents muscle weakening, has a direct effect on bone resorption in a muscle model of rheumatoid arthritis, and inhibition of myostatin leads to preservation of bone tissue.

Obesity and the Development of Arthritis Among Adults in the United States Using NHANES Data.

The alarming increase in the prevalence of obesity and arthritis in America in recent times is concerning both in terms of the deleterious health effects on the individuals and economic cost. The wear and tear on the musculoskeletal and the inflammatory effects of obesity may be the reasons for the rise in arthritis among individuals with obesity. To investigate the association between obesity and the development of arthritis among adults in the United States. A total of 17 016 participants were included from the 2012 to 2018 National Health and Nutrition Examination Survey (NHANES). Most of the participants were aged 30 years and above (79.7%). The racial distribution included 64.0% Non-Hispanic whites, 15.3% Hispanics, 11.4% Non-Hispanics blacks, and 9.4% from all other races. Obesity was defined as a body mass index (BMI) > 30 kg/m², and the outcome variable of interest, arthritis status, was self-reported. Survey weighted logistic regression was performed to calculate the odds ratio (OR) and 95% confidence interval controlling for potential confounding factors. Nearly 40% of all participants were individuals with obesity, and 27.5% reported having some form of arthritis. The risk of developing arthritis was higher in individuals with obesity (OR: 1.55, 95% CI: 1.35-1.80), women (OR: 1.94, 95%CI: 1.66-2.28), and individuals 30 years or older (OR: 10.81, 95% CI: 6.36-18.37) with non-Hispanic whites being the most affected race. The C-reactive protein (CRP) and white blood cell count (WBC) levels were higher in all individuals with obesity even though there was no statistical difference between individuals with obesity with and without arthritis. Obesity substantially heightens the risk of developing arthritis due to the mechanical stress on weight-bearing joints and subsequent chronic-low level inflammation contributing to disease progression.

Determination of inflammation by TNF-alpha and IL-10 levels in obese children and adolescents.

Background: childhood obesity is one of the major health problem worldwide. Obesity is associated with low-level chronic inflammation resulting from inflammatory cytokine release in white adipose tissue. We aim to specify inflammatory markers tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in children and adolescents to determine their relationship with obesity. Materials and methods: forty obese patients and 46 controls were included in the study from the pediatric clinic. Blood samples from the study group were centrifuged, and the sera were stored at -80 °C after separation. Serum levels of TNF-alpha and IL-10 were determined using Human ELISA kits for TNF-alpha and IL-10. Results: serum samples from 86 children, including 45 girls (52.3 %) in the study group, were analyzed for TNF-alpha and IL-10 levels. TNF-alpha levels in the obese and control groups were 1.04 ± 0.79 and 0.60 ± 0.72 pg/ml, respectively (p = 0.010). Also, IL-10 levels in the obese and control groups were 0.76 ± 0.62 and 1.54 ± 0.71 pg/ml, respectively (p < 0.001). Gender was not identified as a factor for serum TNF-alpha and IL-10 levels (p = 0.281 and p = 0.477, respectively). Moreover, white blood cell (WBC) and serum C-reactive protein (CRP) levels were higher in the obese patient group than in the control group (p = 0.002 and p = 0.010, respectively). Conclusion: TNF-alpha levels were higher than control in obese patients and it was important in terms of showing that obesity triggers inflammation in the body. IL-10 levels, which inhibit inflammation, were lower in obese patients than controls.

Иммуновоспалительные механизмы старения мочевого пузыря.

Introduction. Despite the absence of a generally accepted theory explaining the mechanisms of aging, existing scientific data indicate a close relationship between aging and chronic low-grade inflammation (low-grade inflammation). This theory of inflammatory aging (inflame-aging) suggests that aging is accompanied by the development of a chronic inflammatory phenotype, which ultimately leads to fibroplastic transformation of tissues, which manifests itself in a functional deficiency of organs and, in particular, the bladder. Aims. To study the role of free radical oxidation, endothelial dysfunction and low-level age-associated inflammation as universal mechanisms of cellular senescence in the process of age-related detrusor rearrangement in experimental animals. Materials and methods. Two groups of laboratory animals were used in the experiment: group 1 (30-month-old white mongrel rats, n=10) and group 2 (10- month-old white mongrel rats, n=10). Markers of low-level age-associated inflammation (TNF-α, IL-6, IL1RA), endothelial dysfunction (ET-1, IL-1β, ESM1), profibrotic status (TGF beta 1 and CTGF), and free radical oxidation (8-isoprostane) were determined in blood and bladder homogenate, malonic dialdehyde, diene conjugates).The Student's criterion was used to compare two groups with a normal distribution. Results and discussion. It was shown that with age in experimental animals, the levels of inflammation markers (TNF-α, IL-6, IL1RA), endothelial dysfunction (ET-1, IL-1β, ESM1), lipid peroxidation (diene conjugates, silicone dialdehyde) and profibrotic cytokines (TGF beta 1 and CTGF) increased, while the levels of antioxidant activity (catalase) decreased statistically significantly.This pattern was revealed both at the systemic (blood plasma) and organ levels (bladder wall). Conclusion. The results of our experimental study confirm the role of chronic low-level inflammation in fibrosis-mediated inflammatory aging of organs and, in particular, in age-associated bladder reconstruction.

Molecular dynamic of omega-3 compounds as an anti-obesity agent into GPR-120 receptor

Obesity is a cause of comorbid diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension which is based on low-level chronic inflammation. The GPR-120 receptor plays a role in insulin sensitization which is related to diabetes mellitus which is a comorbid obesity. Omega-3 fatty acids are believed to possess anti-inflammatory properties, hence potentially serving as a preventive measure against obesity-related comorbidities. The aim of this study is to do a stability analysis of the binding affinity between nine specific chemicals derived from omega-3 and the active site of the human GPR120 receptor using molecular dynamics simulations. Docking analysis was performed using Discovery Studio Visualizer, AutoDock Tools 1.5.6, and molecular dynamic simulation with AMBER 16. In this study, we used neurotensin 8–13 as a natural ligand to bind with the neurotensin receptor. Based on the neurotensin receptor docking results, the ΔG values for the following compounds are close to the values for neurotensin 8–13 -6.41 kcal/mol; docosahexaenoic acid -8.96 kcal/mol; eicosapentaenoic acid -7.41 kcal/mol; and heneicosapentaenoic acid -6.34 kcal/mol. Neurotensin 8–13 forms hydrogen bonds with TYR146, ARG213, and PHE344 of the neurotensin receptor, whereas docosahexaenoic acid forms hydrogen bonds with TYR146. Meanwhile, the average RMSD fluctuations for each system, namely docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid, were 0.672, 0.437, and 0.650, respectively. The SASA of the neurotensin receptor-ligand complex showed similar fluctuations, with the average values for docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid being 230.40, 229.89, and 230.20 nm2.

Beyond Inflammaging: The Impact of Immune System Aging on Age-Related Muscle Decline, Results From the InCHIANTI Study.

Aging is characterized by chronic low-level inflammation and is associated with geriatric syndromes such as sarcopenia and frailty. Our aim was to evaluate the longitudinal variation of muscle area, muscle quality, and muscle strength, relative to the variation of leukocyte-derived markers, and to assess the presence of a pathway of associations among derived leukocyte ratios, and the components of muscle health. The InCHIANTI is a longitudinal cohort study of aging that began in 1998 with follow-up visits every 3 years. Out of the 1 453 participants enrolled at baseline, this study includes 1 179 participants with complete data. Muscle strength was assessed by hand grip strength test, whereas muscle density and fat area were considered as indirect markers of muscle quality, derived from peripheral quantitative computed tomography of the calf. Muscle area was associated with neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, and body mass index (BMI). Muscle density variation over time was inversely associated with age, comorbidities, and BMI, while being positively associated with monocyte-to-lymphocyte ratio (ML-ratio) and male gender. Fat area was inversely associated with age, interleukine-6 (IL-6), male gender, and NL-ratio, while being positively associated with ML-ratio, comorbidities, and BMI. Handgrip strength decreased with age, IL-6 levels, comorbidities, and NL-ratio, but increased with ML-ratio, being male, and having a higher BMI. In a path-analysis model, ML-ratio positively correlates with muscle mass, density, and strength, while NL-ratio only correlates inversely with muscle mass and density. NL-ratio and ML-ratio are associated with aging and may be implicated in age-related mechanisms that affect body composition and muscle strength. These ratios may represent a link between aging of the immune system and decline of muscle health with aging. However, further studies are needed to identify their usefulness for early detection of sarcopenia, myosteatosis, and frailty in the older adult.

The Evaluation of Serum Endocan, Interleukin-6, and CRP Levels Following Sleeve Gastrectomy.

The excessive accumulation of fat tissue in obesity is the source of chronic low-level inflammation and causes future dysmetabolic and cardiovascular disorders. Removal of this excessive fat tissue with the aid of bariatric surgery (BS) techniques, such as sleeve gastrectomy, may reverse adverse inflammatory outcomes. The aim of this study is to investigate the impact of sleeve gastrectomy on inflammatory markers, specifically endocan, IL-6, and CRP, in individuals with obesity. Thirty-two patients with class 3 obesity and class 2 obesity + comorbidities were enrolled in the study. Clinical characteristics including age, comorbidity, body mass index (BMI), waist, and hip circumferences of the participants were noted before and 3 months after sleeve gastrectomy. Blood samples were collected during those periods to assess biochemical features such as serum endocan, interleukin-6 (IL-6), C-reactive peptide, fasting insulin, glycosylated hemoglobin A1c levels, and lipid panel. A statistical package program was used for the analysis of those parameters, and p<0.05 was accepted as significant at a 95.0% confidence interval. BMI reduced from 43.55±6.78 to 36.16±6.14 kg/m2 within 3 months following BS (p<0.001). Preoperative serum endocan, IL-6, and CRP levels were correlated with BMI, and in line with BMI reduction, their serum levels decreased after BS (p<0.05). HOMA-IR also reduced after BS, and both in the pre and post-BS periods correlated with BMI, IL-6, endocan, and CRP levels (p<0.05). The mean total body weight loss was 20.4% within 3 months post-BS. BS techniques are effective in weight loss and reversing the inflammatory processes caused by obesity. Serum endocan, IL-6, and CRP levels are promising markers for describing obesity-related inflammation and objectively checking the alleviation of inflammation following BS.

P-670 Altered immunological conditions in women with PCOS and its correlation with the development and progression in infertile women with severe polycystic ovaries

Abstract Study question What is the impact of the dysfunctional lymphoid cells on the development and progression in infertile women with severe polycystic ovaries syndrome (SPCOS). Summary answer The dysfunctional lymphoid cells in immune system was deeply correlated with follicular remodeling, which prompting the progression of SPCOS. What is known already PCOS has been confirmed as a low-level chronic inflammation impacting on ovulation and luteinization regulated by a cytokine-mediated inflammatory response orchestrated by lymphocytes, granulocytes, and macrophages. However, the exact relationship between immunologic dysfunction and the pathogenesis of PCOS is still not clarified. Study design, size, duration A prospective cohort study including a total of 129 women aged 18 to 35 years were enrolled. PCOS patients with polycystic ovaries (ultrasound measurement of the number of ≥ 80 follicles ≥3 mm in diameter) were referred to SPCOS in this study. Peripheral Blood (PB) were collected to detect the immunological changes by using flow cytometry: CD8+ T cell (CD3+,CD8+); CD4+ T cell (CD3+,CD4+); NK cell (CD45+,CD3-,CD56+); NKT cell (CD45+,CD3+,CD56+); Treg cell (CD4+CD25hi); B cell (CD3-CD19+). Participants/materials, setting, methods PB from SPCOS cohort (n = 64) and healthy controls (n = 115) were collected to detect the immunological conditions. Furthermore, the discarded tissues from SPCOS patients (n = 5) who needed to avoid OHSS by surgical ovarian wedge resection and women undergoing fertility preservation procedures (n = 3) were digested to single cell suspension, which were used to outline the ovarian homeostasis changes by using scRNA-seq. Main results and the role of chance Peripheral blood NK cells from SPCOS patients were significantly decreased than those from healthy group (10.7% vs. 14.9 ± 6.2%, p = 0.04). Conversely, NKT cells in the PB of the SPCOS women were 11.2% vs. 6.9 ± 3.5% (P = 0.02), while B lymphocytes were 15.6% vs. 12.6 ± 4.2% (P = 0.04), compared to healthy controls. Furthermore, the immune cells and distinct cellular clusters of SPCO were disturbed in severe polycystic ovaries. The CD8+ T cell populations in ovarian of SPCOS group were strongly decreased (32.49% vs.22.35%, p &amp;lt; 0.001) and T cell activation signaling was downregulated by lowly expressed PTPRC, APBB1IP, LCP11 and MX12. Besides, the cytotoxicity-associated genes IFNG and TNF were highly expressed, especially in CD4+ T cells. The chemokines released by activated CD4+ T cells may increase the production and recruitment of CD8+ T cell and induce the compositional and functional alteration of ovarian, thereby prompting the progression of PCOS. Limitations, reasons for caution The study group is limited and transcriptome analysis covers much, but not enough. Although suggestive associations between immunological conditions and the severity of PCOS have concluded, additional animal models studies should be conducted to confirm our findings further. Wider implications of the findings The expression profiles of lymphoid cells provide deep insight into the molecular mechanisms of PCOS. Signaling receptors and gene data set will aid in future studies on the interorgan communication. It also facilitated discovery of novel biomarker for PCOS diagnosis and new immunological treatment. Trial registration number Not applicable

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Aspalathus linearis-a plant widely consumed as Rooibos tea-are increasingly being investigated for their positive effects on various health issues including inflammation. The aim of our study was to examine the effect of Rooibos extract on obesity and the associated low-grade chronic inflammatory state by testing antioxidant activity, cytokine secretions, macrophage polarization and the differentiation of human adipocytes through the development of adipospheroids. Rooibos extract significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFN-γ, IL-12, IL-2 and IL-17a) in human leukocytes. Additionally, Rooibos extract down-regulated LPS-induced macrophage M1 polarization, shown by a significant decrease in the expression of pro-inflammatory cytokines: TNFα, IL-8, IL-6, IL-1β and CXCL10. In addition, Rooibos inhibited intracellular lipid accumulation and reduced adipogenesis by decreasing the expression of PPARγ, Ap2 and HSL in adipospheroids. A significant decrease in leptin expression was noted and this, more interestingly, was accompanied by a significant increase in adiponectin expression. Using a co-culture system between macrophages and adipocytes, Rooibos extract significantly decreased the expression of all studied pro-inflammatory cytokines and particularly leptin, and increased adiponectin expression. Thus, adding Rooibos tea to the daily diet is likely to prevent the development of obesity associated with chronic low-level inflammation.