Chronic Low-grade Systemic Inflammation Research Articles

Soluble P2X7 Receptor Plasma Levels in Obese Subjects before and after Weight Loss via Bariatric Surgery

Obesity is a systemic disease frequently associated with important complications such as type 2 diabetes and cardiovascular diseases. It has also been proven that obesity is a disease associated with chronic low-grade systemic inflammation and that weight loss improves this low-grade chronic inflammatory condition. The P2X7 purinergic receptor (P2X7R), belonging to the family of the receptors for extracellular ATP, is a main player in inflammation, activating inflammasome and pro-inflammatory cytokine production. In this study, we evaluated the plasma levels of soluble P2X7R (sP2X7R) measured in a group of obese patients before and one year after bariatric surgery. Furthermore, we evaluated the relation of sP2X7R to inflammatory marker plasma levels. We enrolled 15 obese patients who underwent laparoscopic sleeve gastrectomy, evaluating anthropometric parameters (weight, height, BMI and waist circumference) before and after surgery. Moreover, we measured the plasma levels of inflammatory markers (CRP, TNFα and IL-6) before and after weight loss via bariatric surgery. The results of our study show that one year after bariatric surgery, obese patients significantly decrease body weight with a significant decrease in CRP, TNF-alfa and IL-6 plasma levels. Similarly, after weight loss, obese subjects showed a significant reduction in sP2X7R plasma levels. Moreover, before surgery, plasma levels of sP2X7R were inversely related with those of CRP, TNF-alfa and IL-6. Given the role of P2X7R in inflammation, we hypothesized that, in obese subjects, sP2X7R could represent a possible marker of chronic low-grade inflammation, hypothesizing a possible role as a mediator of obesity complications.

Influence of Breastfeeding on the State of Meta-Inflammation in Obesity-A Narrative Review.

Obesity has become an emerging health issue worldwide that continues to grow in females of reproductive age as well. Obesity, as a multisystem and chronic disease, is associated with metabolic inflammation, which is defined as chronic low-grade systemic inflammation mediated by, i.a., adipose tissue macrophages. Lactation has been proven to have a beneficial influence on maternal health and could help restore metabolic balance, especially in the state of maternal obesity. In this review, we aimed to analyze the influence of breastfeeding on chronic low-grade meta-inflammation caused by obesity. We performed a comprehensive literature review using the PubMed, Science Direct, and Google Scholar electronic databases. For this purpose, we searched for "metabolic inflammation"; "meta-inflammation"; "obesity"; "breastfeeding"; "fetal programming"; "energy metabolism"; "postpartum"; "immunity"; "immune system"; and "inflammation" keyword combinations. While the clinical impact of breastfeeding on maternal and offspring health is currently well known, we decided to gain insight into more specific metabolic effects of adiposity, lipid, and glucose homeostasis, and immunological effects caused by the activity of cytokines, macrophages, and other immune system cells. Further research on the immunological and metabolic effects of breastfeeding in obese patients is key to understanding and potentially developing obesity therapeutic strategies.

Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Adherence to healthy lifestyle was associated with an attenuation of the risk of chronic kidney disease from metabolic dysfunction–associated fatty liver disease: Results from two prospective cohorts

AimsNon-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction–associated fatty liver disease (MAFLD) are important risk factors of chronic kidney disease (CKD). Whether adherence to a healthy lifestyle can modify these effects remain unknown. This study aimed to evaluate the modification effects of healthy lifestyle on the associations among NAFLD, MAFLD, and the risk of CKD, with taking into the effect of genetic risk. MethodsThe Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH), the UK Biobank Study (UKB). The outcome was incident CKD. The exposures including NAFLD, MAFLD, healthy lifestyle, and a genetic risk score (GRS) for CKD. ResultsAfter 1,135,334 person–year follow-up, we documented 2975 incident CKD cases in the two cohorts. MAFLD and NAFLD were associated with a higher risk of CKD, particularly in patients with MAFLD. In the TCLSIH and UKB, the hazard ratios (95% confidence intervals) of incident CKD for MAFLD were 1.47 (1.30, 1.66) and 1.73 (1.57, 1.91), respectively. Adherence to a healthier lifestyle decreased the risk of CKD from MAFLD with significant interaction effects (TCLSIH: Pinteraction = 0.02; UKB: Pinteraction = 0.04). Participants with a lower CKD–GRS experienced a higher risk of CKD from MAFLD, but achieved two healthy lifestyles can significantly decreased the risk of CKD in patients with MAFLD. ConclusionsMAFLD and NAFLD are associated with a higher CKD risk, particularly MAFLD. Adherence to a healthier lifestyle was associated with a lower risk of CKD from MAFLD. These results highlight the important role of following a healthy lifestyle to prevent CKD.

Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study.

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague-Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis.

Acupuncture as multi-targeted therapy for the multifactorial disease obesity: a complex neuro-endocrine-immune interplay.

The prevalence of obesity has reached pandemic dimensions. It is associated with multiple comorbidities and is becoming a clinical and public health threat. Obesity is a multifactorial disease with a complex pathophysiology and interplay of various systems. A strong interplay exists between the neuro-endocrine system, the immune system with systemic chronic low-grade inflammation, and microbiome dysbiosis that can lead to the development of obesity, which in turn can exacerbate each of these factors, hence creating a vicious cycle. The conventional treatment with lifestyle modifications such as diet, physical exercise, pharmacotherapy, and bariatric surgery does not always result in sufficient weight control thus paving the way for other strategies. As one such strategy, acupuncture is increasingly used worldwide to treat obesity. This narrative review outlines the evidence for this neuro-endocrine-immune interplay in the pathophysiology of obesity. Furthermore, the existing experimental and clinical evidence of acupuncture as a multi-targeted therapy for obesity is explained and future research perspectives are discussed.

Impacts of an 8-week regimen of aged garlic extract and aerobic exercise on the levels of Fetuin-A and inflammatory markers in the liver and visceral fat tissue of obese male rats

Obesity-induced chronic low-grade systemic inflammation is linked to the development of numerous diseases. Fetuin-A is known to affect inflammation and insulin resistance in obesity conditions. Free fatty acid (FFA)-induced proinflammatory cytokine expression in adipocytes occurs only in the presence of both Fetuin-A and toll-like receptor 4 (TLR4) and removing either of them prevented FFA-induced insulin resistance. Aged garlic extract (AGE) and exercise training have anti-inflammatory effects; however, the impact of AGE on Fetuin-A is unknown. We examined the effects of AGE with or without aerobic training (AT) on Fetuin-A and inflammatory markers. Forty healthy male Sprague Dawley rats were randomly assigned to normal diet (ND) (n=8) or high-fat diet (HFD) groups (n=32) and fed for 9 weeks. After 9 weeks ND group continued normal diet, and the HFD group was randomly assigned to the HFD, HFD+AGE (600mg/kg, once daily), HFD+AT (5 days/week), and HFD+AGE+AT groups that were continued for 8 weeks (n=8). The significance of differences among groups was assessed using one-way analysis of variance followed by the post-hoc Tukey test. Statistically significant differences were considered for p<0.05. AGE, AT, and AGE+AT significantly decreased body weight, plasma Fetuin-A, HOMA-IR, mRNA and protein levels of Fetuin-A and NFƙB in the liver and mRNA and Protein levels of Fetuin-A, TLR4 and NFƙB in visceral adipose tissue (VAT) compared to HFD. However, only AGE+AT significantly decreased TLR4 protein levels in the liver. Although AT and AGE reduce Fetuin-A and inflammatory markers, a combination of the two may be more effective at lowering inflammation.

Serum immunoglobulin concentration and the risk of type 2 diabetes mellitus in adults in Tianjin City: a prospective cohort study

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q1 to Q4 according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q1, subjects in group Q4 with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q4 with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q4 with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (Ptrend=0.018, Ptrend=0.010) and increased with the increase of serum IgA concentrations (Ptrend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, Ptrend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.

Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation

Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent.Graphical

Allergic Diseases and Childhood Obesity: A Detrimental Link?

Several epidemiological studies have described childhood obesity as a risk factor for atopic disease, particularly asthma. At the same time, this association seems to be more conflicting for allergic rhinitis, atopic dermatitis, and chronic urticaria. This article aims to deepen the possibility of a relationship between childhood obesity and allergic diseases. As regards asthma, the mechanical and inflammatory effects of obesity can lead to its development. In addition, excess adiposity is associated with increased production of inflammatory cytokines and adipokines, leading to low-grade systemic inflammation and an increased risk of asthma exacerbations. Allergic rhinitis, atopic dermatitis, food allergies, and chronic urticaria also seem to be related to this state of chronic low-grade systemic inflammation typical of obese children. Vitamin D deficiency appears to play a role in allergic rhinitis, while dyslipidemia and skin barrier defects could explain the link between obesity and atopic dermatitis. Starting from this evidence, it becomes of fundamental importance to act on body weight control to achieve general and allergic health, disentangling the detrimental link between obesity allergic diseases and childhood obesity. Further studies on the association between adiposity and atopy are needed, confirming the biologically active role of fat tissue in the development of allergic diseases and exploring the possibility of new therapeutic strategies.

The role of endothelial dysfunction, microcirculatory disorders, and hypoxia as mechanisms for the formation of lung lesions

In a review article, the authors consider the significance of endothelial dysfunction, microcirculation disorders, and hypoxia in the development of lung diseases and in the comorbid course of a number of other diseases of the internal organs. The role of endotheliocytes in the systemic response to inflammatory processes in the case of damage to the bronchopulmonary system is considered. Endothelial cells counteract pathogens in the blood and send signals warning of infection, invasion, or injury. The importance of the anticoagulant and antithrombotic properties of the endothelium (including the pulmonary one), which contribute to the fight against thrombosis, is emphasized. It is indicated that endothelial cells have an endogenous mechanism to combat platelet activation. This function depends on the surface expression of ecto-ATPase, CD39, and the release of nitric oxide and prostacyclin. Attention is paid to the importance of activation of the renin-angiotensin-aldosterone system both through angiotensin-II and through aldosterone. The authors stressed the importance of endothelial dysfunction as an imbalance between the factors of relaxation and constriction, coagulation, and fibrinolysis, which provide hemostasis of the main vital regulatory systems, and the stage of disease compensation (via the participation of nitric oxide). Microcirculation disorders and hypoxia are considered phenomena that are compatible in pathogenesis not only with pulmonary diseases but also as common comorbid syndromes with other diseases of the internal organs. This is explained by the fact that the common links are chronic oxidative stress, the reaction of the immune system to damage, the formation of a low-grade chronic systemic inflammation syndrome, a violation of the microcirculation process, and an increase in hypoxic and ischemic processes. The importance of knowledge about the mechanisms of development of endothelial dysfunction, microcirculation disorders, and hypoxia for therapeutic and rehabilitation tactics is emphasized.

A narrative review of the physiology and health effects of burnout associated with veterinarian-pertinent occupational stressors.

Chronic workplace stress and burnout are serious problems in veterinary medicine. Although not classified as a medical condition, burnout can affect sleep patterns and contributes to chronic low grade systemic inflammation, autonomic imbalance, hormonal imbalances and immunodeficiencies, thereby increasing the risks of physical and psychological ill health in affected individuals. Cultural misconceptions in the profession often lead to perceptions of burnout as a personal failure, ideas that healthcare professionals are somehow at lower risk for suffering, and beliefs that affected individuals can or should somehow heal themselves. However, these concepts are antiquated, harmful and incorrect, preventing the design of appropriate solutions for this serious and growing challenge to the veterinary profession. Veterinarians must first correctly identify the nature of the problem and understand its causes and impacts before rational solutions can be implemented. In this first part of two companion reviews, burnout will be defined, pathophysiology discussed, and healthcare and veterinary-relevant occupational stressors that lead to burnout identified.

Dietary pulses as a means to improve the gut microbiome, inflammation, and appetite control in obesity.

A dysbiotic intestinal microbiome has been linked to chronic diseases such as obesity, which may suggest that interventions that target the microbiome may be useful in treating obesity and its complications. Appetite dysregulation and chronic systemic low-grade inflammation, such as that observed in obesity, are possibly linked with the intestinal microbiome and are potential therapeutic targets for the treatment of obesity via the microbiome. Dietary pulses (e.g., common beans) are composed of nutrients and compounds that possess the potential to modulate the gut microbiota composition and function which can in turn improve appetite regulation and chronic inflammation in obesity. This narrative review summarizes the current state of knowledge regarding the connection between the gut microbiome and obesity, appetite regulation, and systemic and adipose tissue inflammation. More specifically, it highlights the efficacy of interventions employing dietary common beans as a means to improve gut microbiota composition and/or function, appetite regulation, and inflammation in both rodent obesity and in humans. Collectively, results presented and discussed herein provide insight on the gaps in knowledge necessary for a comprehensive understanding of the potential of beans as a treatment for obesity while highlighting what further research is required to gain this understanding.

Platelet indices in overweight and obese children.

Significant differences were observed in terms of PLT, PCT, MPV/PLT, and PDW/PLT between overweight, obese, and normal-weight children. • Obesity is associated with a chronic low-grade systemic inflammation. • Platelets play a crucial role in coagulation, hemostasis, thrombosis, immunomodulatory processes, inflammation, and atherothrombosis. • Significant differences were observed in terms of PLT, PCT, MPV/PLT, and PDW/PLT between overweight, obese, and normal-weight children. • Overweight and obese children with insulin resistance had higher PLT and lower MPV/PLT and PDW/PLT ratios than the children without insülin resistance.

Relationship between dietary pattern and depressive symptoms: an international multicohort study

BackgroundSeveral previous studies have shown that dietary patterns are associated with the incidence of depressive symptoms. However, the results have been inconsistent. This study aimed to prospectively investigate the association between dietary patterns and the risk of depressive symptoms in two large cohort studies.MethodsThe Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study included a total of 7,094 participants living in Tianjin, China from 2013 to 2019, and the UK Biobank cohort study includes 96,810 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. All participants were free of a history of cardiovascular disease (CVD), cancer, and depressive symptoms at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated food frequency questionnaire in TCLSIH or Oxford WebQ in UK Biobank. Depressive symptoms were evaluated using the Chinese version of the Zung Self-Rating Depression Scale (SDS) in TCLSIH or hospital inpatient records in UK Biobank. Cox proportional hazards regression models were used to estimate the association between dietary patterns and depressive symptoms.ResultsA total of 989, and 1,303 participants developed depressive symptoms during 17,410 and 709,931 person-years of follow-up. After adjusting for several potential confounders, the multivariable HRs (95% CIs) of the depressive symptoms were 0.71 (0.57, 0.88) for traditional Chinese dietary pattern, 1.29 (1.07, 1.55) for processed animal offal included animal food dietary pattern, and 1.22 (1.02, 1.46) for sugar rich dietary pattern in TCLSIH (all Q4 vs Q1). In the UK Biobank, the HRs (95% CIs) of depressive symptoms were 1.39 (1.16, 1.68) for processed food dietary pattern (Q4 vs Q1), 0.90 (0.77, 1.00) for healthy dietary pattern (Q3 vs Q1), and 0.89 (0.75, 1.05) for meat dietary pattern (Q4 vs Q1) in the final adjusted model.ConclusionDietary patterns rich in processed foods were associated with a higher risk of depressive symptoms, and following a traditional Chinese dietary pattern or healthy dietary pattern was associated with a lower risk of depressive symptoms, whereas meat dietary pattern was not associated.

Pharmacotherapies in Older Adults with COPD: Challenges and Opportunities.

Older adults have a higher prevalence of chronic obstructive pulmonary disease (COPD), which will likely increase substantially in the coming decades owing to aging populations and increased long-term exposure to risk factors for this disease. COPD in older adults is characterized by low-grade chronic systemic inflammation, known as inflamm-aging. It contributes substantially to age-associated pulmonary changes that are clinically expressed by reduced lung function, poor health status, and limitations in activities of daily living. In addition, inflamm-aging has been associated with the onset of many comorbidities commonly encountered in COPD. Furthermore, physiologic changes that are often seen with aging can influence the optimal treatment of older patients with COPD. Therefore, variables such as pharmacokinetics, pharmacodynamics, polypharmacy, comorbidities, adverse drug responses, drug interactions, method of administration, and social and economic issues that impact nutrition and adherence to therapy must be carefully evaluated when prescribing medication to these patients because each of them alone or together may affect the outcome of treatment. Current COPD medications focus mainly on alleviating COPD-related symptoms, so alternative treatment approaches that target the disease progression are being investigated. Considering the importance of inflamm-aging, new anti-inflammatory molecules are being evaluated, focusing on inhibiting the recruitment and activation of inflammatory cells, blocking mediators of inflammation thought to be important in the recruitment or activation of these inflammatory cells or released by these cells. Potential therapies that may slow the aging processes by acting on cellular senescence, blocking the processes that cause it (senostatics), eliminating senescent cells (senolytics), or targeting the ongoing oxidative stress seen with aging need to be evaluated.

Morphofunctional changes of microglia in adult and old Wistar rats

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases leading to dementia. There is no effective treatments for this disease so far, as well as a consensus concerning the mechanisms of its pathogenesis initiation. Obtaining data on them in vivo is possible only by modeling neurodegeneration in laboratory animals. Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases leading to dementia. There is no effective treatments for this disease so far, as well as a consensus concerning the mechanisms of its pathogenesis initiation. Obtaining data on them in vivo is possible only by modeling neurodegeneration in laboratory animals. Among the various theories of the initiation of neurodegeneration, the impact of microglia is vigorously studied recently, as well as inflammaging, which is a term for chronic age-related low-grade systemic inflammation. It manifests in the increasing number of senescent cells with senescence-associated secretory phenotype (SASP). Eventually, it leads to manifestation and progression of age-related diseases, such as AD. The aim of the study was to evaluate age-related changes in microglia, pro- and anti-inflammatory cytokines expression levels in the brain, as well as ones of microglial activation, and also subpopulations of lymphocytes in peripheral blood. We used male Wistar rats of two age groups, which were composed of old (age 24 months) and adult (age 3 months) rodents, without any additional exposure. In the hippocampus, morphological changes in microglia were assessed on preparations stained with antibodies to Iba1. In the prefrontal cortex, RT-qPCR was used to study the level of expression of pro-inflammatory IL-6 and TNFa, anti-inflammatory IL-10 and TGF-b cytokines, as well as microglial activation markers iNOS and MMP-9. In the peripheral blood, the relative numbers of the main subpopulations of lymphocytes and monocyte were measured by flow cytometry. It was shown that, compared with adult rats, old animals are characterized by significant changes in the morphology of microglia, an increase in the level of expression of pro-inflammatory and a decrease in anti-inflammatory cytokines, and an increase in microglia activation markers. With aging, a decrease in the percentage of monocytes and B cells in peripheral blood was observed. These data indicate the development of inflammaging, which displays itself in microglia activation, a shift in the balance of cytokine production towards pro-inflammatory ones, and, as a result, activation of the migration of monocytes and B lymphocytes from the blood into tissues. Thus, it is justified to study the role of inflammation in the development of AD in old animals whose physiological state corresponds to that in humans. Further research in this area will expand the understanding of the mechanisms of initiation and progression of neurodegeneration, which is necessary for the development of novel and effective therapeutic approaches to the treatment of AD.

Protection against Microglia Senescence by the Dietary Supplement Dekosilhue® in BV2 Cells: A New Perspective for Obesity and Related Complications

Growing evidence indicates chronic low-grade systemic inflammation as a major pathophysiological mechanism of obesity. Systemic inflammation provokes an immune response in the brain through the activation of microglia that results in the development of neuroinflammation, cellular senescence, and occurrence of neurological dysfunction. In the efforts to identify an innovative intervention with potential efficacy on obesity and associated complications, our aim was to study the capability of the dietary supplement Dekosilhue® (DKS), successfully used for improving the control of body weight, to attenuate microglia senescent phenotype. Microglia senescence was induced by intermittent stimulation of BV2 cells with LPS 500 ng/mL every 72 h for 4 h/day, over a period of 10 days. DKS (100 µg/mL) treatment reduced ß-galactosidase activity and expression, the formation of senescence-associated heterochromatin foci to control levels, and increased cell viability of senescent BV2 (2 folds of control). DSK reduced the expression of Nuclear Factor-kB (NF-kB) (20% lower than control), a key molecule involved in the acquisition of the senescence-associated secretory phenotype (SASP). DKS promoted a neuroprotective effect by increasing the cell viability of SH-SY5Y neuronal cells exposed to the senescent BV2 conditioned medium to values of non-senescent cells. In conclusion, DKS attenuated the senescent microglia phenotype, showing senotherapeutic activity that might be further investigated as adjunctive intervention for obesity and obesity-related neurological disturbances.

Composition of subgingival microbiota associated with periodontitis and diagnosis of malignancy-a cross-sectional study.

Periodontitis is one of the world's most prevalent infectious conditions, affecting between 25 and 40% of the adult population. It is a consequence of the complex interactions between periodontal pathogens and their products, which trigger the host inflammatory response, chronic inflammation, and tissue destruction. Chronic systemic low-grade inflammation is involved in numerous diseases, and it is also known that long-lasting inflammation and chronic infections predispose one to cancer. Here, we characterized and compared the subgingival microbiota associated with periodontitis and diagnosis of malignancy in a longitudinal 10-year follow-up study. The study was conducted on 50 patients with periodontitis and 40 periodontally healthy individuals. The recorded clinical oral health parameters were periodontal attachment loss (AL), bleeding on probing (BOP), gingival index (GI), probing depth (PD), and plaque index (PI). Subgingival plaque was collected from each participant, from which DNA was extracted, and 16S rRNA gene amplicon sequencing performed. Cancer diagnoses data were collected between the years 2008-2018 from the Swedish Cancer Registry. The participants were categorized based on having cancer at the time of sample collection (CSC), having developed cancer later (DCL), and controls without any cancer. The most abundant phyla across all 90 samples were Actinobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Fusobacteria. At the genus level, Treponema, Fretibacterium, and Prevotella were significantly more abundant in samples of periodontitis patients compared to non-periodontitis individuals. With regard to samples of cancer patients, Corynebacterium and Streptococcus were more abundant in the CSC group; Prevotella were more abundant in the DCL group; and Rothia, Neisseria, and Capnocytophaga were more abundant in the control group. In the CSC group, we also found that the presence of periodontal inflammation, in terms of BOP, GI, and PLI, significantly correlated with species belonging to the genera Prevotella, Treponema, and Mycoplasma. Our results revealed that several subgingival genera were differentially enriched among the studied groups. These findings underscore the need for further research to fully understand the role that oral pathogens may play in the development of cancer.

15 Unique yeast-derived prebiotic supports joint health and reduced systemic inflammation in senior horses

Senior horses are commonly afflicted with inflammation-related conditions including chronic or acute joint inflammation, and chronic low-grade systemic inflammation, or “inflamm-aging.” Reducing inflammation, where appropriate, may improve the quality of life and performance of senior horses. To that end, the objective of this trial was to determine whether supplementation of a unique yeast-derived prebiotic (ActivAge®(AA)) to senior horses would promote reduced joint and systemic inflammation. Aged Quarter horses (n = 10; mean age ± SEM = 21.3 ± 1.2yr; mean BW ± SEM = 587.5 ± 10.9kg; mean BCS ± SEM = 6.3 ± 0.2) were utilized in a crossover trial. Horses were randomly assigned to either a control (CON) or treatment (TRT) group. Horses in both groups were offered 4.54 kg/d Purina® Equine Senior® (CP = 14.5%, Ca = 0.76%, P = 0.61%). Horses were offered 1.25% BW as local grass hay (CP = 14.6%, Ca = 0.60%, P = 0.30%) daily. Horses were additionally offered 0.45 kg/d of a pellet containing AA (TRT) or not (CON). Daily ration was split into 2 equal feedings at 0700 and 1300 daily for 42d per period with a 28d washout period during which no TRT or CON pellet was offered. All horses had ad libitum access to fresh clean water and white salt. Serum samples were obtained via jugular venipuncture approximately 2hr post feeding every 2wk foranalysis of the acute phase protein, serum amyloid A (SAA; SAA-Vet, Eiken Chemical Co.). On d42 horses underwent a joint inflammation challenge. Briefly, 1mL of a sterile saline solution containing 0.5ng lipopolysaccharide from E. coli 055:B5 (Sigma-Aldrich) was injected into the radiocarpal joint. The contralateral joint was used as a control with only sterile saline injected. Synovial fluid was collected aseptically immediately before injection and at 5, 24, and 48hr post injection. All data were analyzed via ANOVA utilizing a MIXED procedure in SAS 9.4. Horses in the TRT group had no increase in SAA during supplementation while horses in CON increased by approximately 37% by d42 for a trt x time interaction (P < 0.001). Horses in the CON group in both the control and challenged joint had higher AUC for interleukin-6 (P = 0.02) and tumor-necrosis factor α (P = 0.01) than TRT horses. Interleukin-6 and TNFa were analyzed via species-specific colorimetric assays (RD Systems). Taken together, these data indicate that ActivAge® supplementation reduced systemic inflammation in senior horses while also supporting these horses during a joint inflammation challenge.