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Abstract Background Chronic low-grade inflammation may mediate the relationship between obesity and diabetes, yet clinical research in this area remains scarce. Thus, this study aimed to explore the mediating role of chronic low-grade inflammation in this relationship using the National Health and Nutrition Examination Survey (NHANES). Methods This study involved 2,482 participants enrolled in the NHANES between 2005 and 2016. Based on the complex sampling survey weights of NHANES, logistic regression models were fitted, adjusting for various covariates to investigate the relationship between BMI, INFLA score, and diabetes. Moreover, weighted quantile sum (WQS) regression models were fitted to analyze the proportional contribution of individual components within the INFLA score. Finally, mediation analysis was conducted to quantitatively assess the magnitude of the mediating effect of the INFLA score on the relationship between BMI and diabetes. Results After adjusting for all potential confounding factors, a significant positive correlation was noted between INFLA score and diabetes [OR (95% CI), 1.038(1.003–1.075), p = 0.035]. Additionally, a significant positive correlation was observed between the high INFLA group and diabetes compared to the low INFLA group [OR (95% CI), 1.599(1.031–2.481), p = 0.037]. WQS regression models revealed that the proportional contributions of C-reactive protein, white blood cell count, platelet count, and neutrophil-to-lymphocyte ratio (NLR) were 55.5%, 34.8%, 8.46%, and 1.19%, respectively. Finally, the results of the mediation analysis indicated that the indirect effect of the INFLA score accounted for 10.20%. Conclusions Chronic low-grade inflammation was associated with diabetes and partially mediates the relationship between obesity and diabetes.

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1−/−) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1−/−) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1−/− mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function. [ABSTRACT FROM AUTHOR]

Background: Chronic low-grade inflammation may mediate the relationship between obesity and diabetes, yet clinical research in this area remains scarce. Thus, this study aimed to explore the mediating role of chronic low-grade inflammation in this relationship using the National Health and Nutrition Examination Survey (NHANES). Methods: This study involved 2,482 participants enrolled in the NHANES between 2005 and 2016. Based on the complex sampling survey weights of NHANES, logistic regression models were fitted, adjusting for various covariates to investigate the relationship between BMI, INFLA score, and diabetes. Moreover, weighted quantile sum (WQS) regression models were fitted to analyze the proportional contribution of individual components within the INFLA score. Finally, mediation analysis was conducted to quantitatively assess the magnitude of the mediating effect of the INFLA score on the relationship between BMI and diabetes. Results: After adjusting for all potential confounding factors, a significant positive correlation was noted between INFLA score and diabetes [OR (95% CI), 1.038(1.003–1.075), p = 0.035]. Additionally, a significant positive correlation was observed between the high INFLA group and diabetes compared to the low INFLA group [OR (95% CI), 1.599(1.031–2.481), p = 0.037]. WQS regression models revealed that the proportional contributions of C-reactive protein, white blood cell count, platelet count, and neutrophil-to-lymphocyte ratio (NLR) were 55.5%, 34.8%, 8.46%, and 1.19%, respectively. Finally, the results of the mediation analysis indicated that the indirect effect of the INFLA score accounted for 10.20%. Conclusions: Chronic low-grade inflammation was associated with diabetes and partially mediates the relationship between obesity and diabetes. [ABSTRACT FROM AUTHOR]

Oral health is closely related to systemic health. Common chronic oral diseases, periodontitis and periapical inflammation for example, not only affect the health of oral soft and hard tissues including the alveolar bone and gums, but may also cause changes in systemic conditions such as chronic low-grade inflammation, elevated oxidative stress levels, and dysbiosis of the microbiota. These changes in systemic health can exacerbate the progression of obesity. Therefore, through proactive oral health interventions such as maintaining good oral hygiene habits, modifying dietary structures, and undergoing oral examinations, it is possible to effectively prevent and alleviate inflammatory oral diseases, and actively intervene in obesity. This article delves into the impact of inflammatory oral diseases on obesity and their underlying mechanisms, defines the concept of 'oral proactive healthcare', and systematically summarizes their preventive and therapeutic effects on inflammatory oral diseases, thereby demonstrating the potential of improving obesity through proactive oral health strategies.

Breast cancer (BC) is the most common cancer in women, with 2.3 million diagnoses in 2020. There is growing evidence that lifestyle factors, including dietary factors, particularly the complex interactions and synergies between different foods and nutrients (and not a single nutrient or food), may be associated with a higher risk of BC. The aim of this work was to evaluate how the Italian Mediterranean Index (IMI), the Greek Mediterranean Index, the DASH score, and the EAT-Lancet score can help lower the risk of BC, and analyze if chronic low-grade inflammation may be one of the possible mechanisms through which dietary patterns influence breast cancer risk. We evaluated the effect of adherence to these four dietary quality indices in the 9144 women of the ORDET cohort who completed a dietary questionnaire. The effect of adherence to dietary patterns on chronic inflammation biomarkers was evaluated on a subsample of 552 participants. Hazard ratios (HRs) with 95% confidence intervals (CIs) for BC risk in relation to the index score categories used were estimated using multivariable Cox models adjusted for potential confounders. Regression coefficients (β), with 95% CI for C-reactive protein (CRP), TNF-α, IL-6, leptin, and adiponectin levels in relation to adherence to dietary patterns were evaluated with the linear regression model adjusted for potential confounders. IMI was inversely associated with BC in all women (HR: 0.76, 95% CI: 0.60–0.97, P trend = 0.04), particularly among postmenopausal women (HR: 0.64, 95% CI: 0.42–0.98, P trend = 0.11). None of the other dietary patterns was associated with BC risk. Higher IMI and Greek Mediterranean Index scores were inversely associated with circulating CRP (β: −0.10, 95% CI: −0.18, −0.02, and β: −0.13, 95% CI: −0.21, −0.04). The higher score of the EAT-Lancet Index was instead associated with a higher concentration of circulating levels of CRP (β: 0.10, 95% CI: 0.02, 0.18). In conclusion, these results suggest that adherence to a typical Italian Mediterranean diet protects against BC development, especially among postmenopausal women, possibly through modulation of chronic low-grade inflammation. [ABSTRACT FROM AUTHOR]

ApoB is the main protein of triglyceride-rich lipoproteins and is further divided into ApoB48 in the intestine and ApoB100 in the liver. Very low-density lipoprotein (VLDL) is produced by the liver, contains ApoB100, and is metabolized into its remnants, intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL). ApoB100 has been suggested to play a crucial role in the formation of the atherogenic plaque. Apart from being a biomarker of atherosclerosis, ApoB100 seems to be implicated in the inflammatory process of atherosclerosis per se. In this review, we will focus on the structure, the metabolism, and the function of ApoB100, as well as its role as a predictor biomarker of cardiovascular risk. Moreover, we will elaborate upon the molecular mechanisms regarding the pathophysiology of atherosclerosis, and we will discuss the disorders associated with the APOB gene mutations, and the potential role of various drugs as therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In addition, GDM has been linked to chronic low-grade inflammation with recent research indicating a potential immune dysregulation in pathophysiology and a disparity in regulatory T cells.Objective: This systematic review and meta-analysis aimed to determine whether there is an association between GDM and the level of Tregs in the peripheral blood.Methods: Literature searches were conducted in PubMed, Embase, and Ovid between the 7th and 14th of February 2022. The inclusion criteria were any original studies published in the English language, measuring differentiated Tregs in women with GDM compared with glucose-tolerant pregnant women. Meta-analysis was performed between comparable Treg markers. Statistical tests were used to quantify heterogeneity: τ², χ², and I². Study quality was assessed using a modified version of the Newcastle-Ottawa scale.Results: The search yielded 223 results: eight studies were included in the review and seven in the meta-analysis (GDM = 228, control = 286). Analysis of Tregs across all trimesters showed significantly lower Treg numbers in women with GDM (SMD, −0.76; 95% CI, −1.37, −0.15; I² = 90%). This was reflected in the analysis by specific Treg markers (SMD −0.55; 95% CI, −1.04, −0.07; I² = 83%; third trimester, five studies). Non-significant differences were found within subgroups (differentiated by CD4+FoxP3+, CD4+CD127−, and CD4+CD127−FoxP3) of both analyses.Conclusion: GDM is associated with lower Treg numbers in the peripheral maternal blood. In early pregnancy, there is clinical potential to use Treg levels as a predictive tool for the subsequent development of GDM. There is also a potential therapeutic intervention to prevent the development of GDM by increasing Treg populations. However, the precise mechanism by which Tregs mediate GDM remains unclear. [ABSTRACT FROM AUTHOR]

An unbalanced diet increases the risk of developing a variety of chronic diseases and cancers, leading to higher morbidity and mortality rates worldwide. Low-grade systemic chronic inflammation mediated by the activation of the innate immune system is common to all these pathologies. Inflammation is a biological response of the body and a normal part of host defense to combat the effects of bacteria, viruses, toxins and macronutrients. However, when the innate immune system is constantly activated, it can promote the development of low-grade systemic chronic inflammation, which could play an important role in the development of chronic diseases and cancer. Since most chronic inflammatory diseases are associated with diet, a balanced healthy diet high in anti-inflammatory food components could prevent chronic diseases and cancer. The cells of the body's immune system produce chemokines and cytokines which can have pro-inflammatory and tumor-promoting as well as anti-inflammatory and tumor-fighting functions. A challenge in the future will be to assess whether polymorphisms in immune-related genes may play a role in promoting pro-inflammatory activity. Thanks to this duality, future research on immune regulation could focus on how innate immune cells can be modified to convert a pro-inflammatory and tumor-friendly microenvironment into an anti-inflammatory and anti-tumor one. This review describes inflammatory responses mediated by the innate immune system in various diseases such as hyperglycemia and/or hyperlipemia, obesity, type II diabetes, cardiovascular disease and cancer. [ABSTRACT FROM AUTHOR]

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1−/−) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1−/−) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1−/− mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.

Summary: Background & Aims: The role of nutrition in modulating the inflammatory response is increasingly recognized. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The inflammatory status has been linked to autonomic activity, which can be assessed by the study of heart rate variability (HRV). However, monitoring of HRV for assessment of inflammation in humans has hardly been used. We investigated the potential of HRV as a non-invasive tool to monitor inflammation induced by the caloric load and assessed the effects of sulforaphane on caloric load-induced inflammation in healthy participants. Methods: In this double-blind, crossover, randomized, placebo-controlled trial twelve healthy participants (26.9 (3.6) years) were administered 25 mg of sulforaphane, or placebo followed over 90 min by the standardized high-calorie drink PhenFlex given to induce an inflammatory response. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 were measured in plasma before and two hours after the PhenFlex challenge. Changes in the autonomic function were assessed by HRV on four timepoints. Results: The caloric challenge triggered a significant increase in total power (TP) (P = 0.028) and very low frequency (VLF) component (P = 0.013) 30 min after its administration. Those changes were followed by reduction of TP (P = 0.028) and low frequency (LF) component (P = 0.005), suggesting marked decrease in the sympathetic activity two hours after the caloric load. When sulforaphane was given prior to the caloric challenge, decreased parasympathetic activity was observed via a reduction of RMSSD (P = 0.007), pNN50 (P = 0.013) and HF (P = 0.047). In addition, sulforaphane elicited a pro-inflammatory response as measured by the change of hs-CRP with caloric exposure (sulforaphane 2.7 (4.2) vs. placebo -1.8 (3.1) ng/mL, P = 0.048). The pro-inflammatory effect of sulforaphane was associated with vagal withdrawal and sympathetic dominance as suggested by correlations between the changes in hs-CRP and HF (rs = -0.68, P = 0.029) as well as LF/HF (rs = 0.56, P = 0.093) components assessed before and two hours after the PhenFlex challenge. Conclusions: Monitoring of HRV might be a sensitive tool to follow activity of the inflammatory response in various clinical conditions. The standardized caloric PhenFlex challenge induced significant changes in the autonomic regulation in healthy young individuals. Administration of sulforaphane prior to the caloric challenge caused a pro-inflammatory effect which was accompanied by vagal withdrawal and sympathetic dominance. Trial registration number: NCT05146804 at www.clinicaltrials.gov.

BackgroundGestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In addition, GDM has been linked to chronic low-grade inflammation with recent research indicating a potential immune dysregulation in pathophysiology and a disparity in regulatory T cells.ObjectiveThis systematic review and meta-analysis aimed to determine whether there is an association between GDM and the level of Tregs in the peripheral blood.MethodsLiterature searches were conducted in PubMed, Embase, and Ovid between the 7th and 14th of February 2022. The inclusion criteria were any original studies published in the English language, measuring differentiated Tregs in women with GDM compared with glucose-tolerant pregnant women. Meta-analysis was performed between comparable Treg markers. Statistical tests were used to quantify heterogeneity: τ2, χ2, and I2. Study quality was assessed using a modified version of the Newcastle-Ottawa scale.ResultsThe search yielded 223 results: eight studies were included in the review and seven in the meta-analysis (GDM = 228, control = 286). Analysis of Tregs across all trimesters showed significantly lower Treg numbers in women with GDM (SMD, −0.76; 95% CI, −1.37, −0.15; I2 = 90%). This was reflected in the analysis by specific Treg markers (SMD −0.55; 95% CI, −1.04, −0.07; I2 = 83%; third trimester, five studies). Non-significant differences were found within subgroups (differentiated by CD4+FoxP3+, CD4+CD127−, and CD4+CD127−FoxP3) of both analyses.ConclusionGDM is associated with lower Treg numbers in the peripheral maternal blood. In early pregnancy, there is clinical potential to use Treg levels as a predictive tool for the subsequent development of GDM. There is also a potential therapeutic intervention to prevent the development of GDM by increasing Treg populations. However, the precise mechanism by which Tregs mediate GDM remains unclear.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022309796.

Obesity is an important risk factor and common comorbidity of childhood asthma. Simultaneously, obesity-related asthma, a distinct asthma phenotype, has attracted significant attention owing to its association with more severe clinical manifestations, poorer disease control, and reduced quality of life. The establishment of the gut microbiota during early life is essential for maintaining metabolic balance and fostering the development of the immune system in children. Microbial dysbiosis influences host lipid metabolism, triggers chronic low-grade inflammation, and affects immune responses. It is intimately linked to the susceptibility to childhood obesity and asthma and plays a potentially crucial transitional role in the progression of obesity-related asthma. This review article summarizes the latest research on the interplay between asthma and obesity, with a particular focus on the mediating role of gut microbiota in the pathogenesis of obesity-related asthma. This study aims to provide valuable insight to enhance our understanding of this condition and offer preliminary evidence to support the development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Chronic low-grade inflammation is the common pathological basis of various diseases, and diet is a key factor in regulating the level of chronic low-grade inflammation. Assessing the potential of individual dietary inflammation can timely understand the impact on the level of chronic low-grade inflammation in the body, and help develop and implement personalized dietary management plans to promote healthy dietary behavior and reduce disease risk. This article reviews the potential evaluation tools for dietary inflammation both domestically and internationally, including their characteristics, main content, current application status, and limitations. It aims to provide reference for the development and rational selection of evaluation tools for dietary inflammation potential in China, and provide scientific basis and theoretical basis for the formulation of dietary prevention and control strategies in China. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cancer in women, with 2.3 million diagnoses in 2020. There is growing evidence that lifestyle factors, including dietary factors, particularly the complex interactions and synergies between different foods and nutrients (and not a single nutrient or food), may be associated with a higher risk of BC. The aim of this work was to evaluate how the Italian Mediterranean Index (IMI), the Greek Mediterranean Index, the DASH score, and the EAT-Lancet score can help lower the risk of BC, and analyze if chronic low-grade inflammation may be one of the possible mechanisms through which dietary patterns influence breast cancer risk. We evaluated the effect of adherence to these four dietary quality indices in the 9144 women of the ORDET cohort who completed a dietary questionnaire. The effect of adherence to dietary patterns on chronic inflammation biomarkers was evaluated on a subsample of 552 participants. Hazard ratios (HRs) with 95% confidence intervals (CIs) for BC risk in relation to the index score categories used were estimated using multivariable Cox models adjusted for potential confounders. Regression coefficients (β), with 95% CI for C-reactive protein (CRP), TNF-α, IL-6, leptin, and adiponectin levels in relation to adherence to dietary patterns were evaluated with the linear regression model adjusted for potential confounders. IMI was inversely associated with BC in all women (HR: 0.76, 95% CI: 0.60–0.97, P trend = 0.04), particularly among postmenopausal women (HR: 0.64, 95% CI: 0.42–0.98, P trend = 0.11). None of the other dietary patterns was associated with BC risk. Higher IMI and Greek Mediterranean Index scores were inversely associated with circulating CRP (β: −0.10, 95% CI: −0.18, −0.02, and β: −0.13, 95% CI: −0.21, −0.04). The higher score of the EAT-Lancet Index was instead associated with a higher concentration of circulating levels of CRP (β: 0.10, 95% CI: 0.02, 0.18). In conclusion, these results suggest that adherence to a typical Italian Mediterranean diet protects against BC development, especially among postmenopausal women, possibly through modulation of chronic low-grade inflammation.

ContextOsteoarthritis (OA) of the knee is common and is associated with other chronic diseases and early mortality. OA is often described as a “wound that does not heal” because a local innate immune response gets dysregulated. Tai Chi is an aerobic mind-body practice that is recommended in national and international clinical practice guidelines as a treatment for OA of the knee. This review addressed two questions: What causes immune dysregulation in the knee? and Why is Tai Chi an effective treatment?Recent findingsThere is now a good understanding of what causes OA of the knee at the cellular level. OA begins in the synovium from a phenotypic shift in synovial macrophages in response to tissue damage. The synovial macrophages release inflammatory cytokines, as part of the first phase of the normal healing and repair process. Cytokines communicate to other cells that there has been damage. This stimulates chondrocytes, osteoblasts, and fibroblasts to release inflammatory cytokines as well. When tissue damage is repetitive, there is repetitive release of inflammatory cytokines, and the normal healing process stops. The most common cause of tissue damage is from abnormal biomechanical forces on the knee that arise from trauma, injury, and misalignment. Tissue damage is made worse when there is systemic low-grade inflammation associated with other chronic conditions. Pain and stiffness often result in decreased physical activity, which leads to muscle weakness, progressive instability of the joint, and an increased risk of falls, further injuring the knee. Tai Chi improves alignment, optimizes the biomechanical forces on the knee, strengthens the lower limbs, and decreases systemic inflammation. Tai Chi improves balance and decreases the risk of falls and further injury. There is clinical and experimental evidence to suggest that by removing the causes of cell dysregulation, Tai Chi enables the normal healing and repair process to resume.ConclusionKnee OA is a wound that does not heal primarily because repetitive adverse forces on the knee cause synovial macrophages and then local chondrocytes, osteocytes and fibroblasts to dysregulate and stop the normal healing and repair process. Tai Chi mitigates adverse forces on the knee and stabilizes the joint, creating the conditions whereby the normal healing and repair process can resume. Further research is needed.

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.

Introduction: Chitotriosidase-1 (CHIT-1) is a marker of macrophage activation and recently attributed to type 2 diabetes mellitus (T2DM). However, its role in the development and progression of diabetic kidney disease (DKD) has been sparsely discussed in the recent literature. Materials and Methods: In this cross-sectional exploratory study, 81 participants with T2DM were classified into two groups based on the presence of DKD. Their anthropometric, biochemical, and pathological profiles were estimated. Circulatory CHIT-1 concentration was determined using the enzyme-linked immuno-sorbent assay (ELISA) in plasma. Results: CHIT-1 was significantly elevated in diabetic nephropathy, independent of age and gender. It is associated with severity of kidney disease, as assessed using urinary protein-creatinine ratio (uPCR) in a multiple linear regression model, independent of age, gender, diabetes duration, and insulin resistance. CHIT-1 positively predicted the likelihood of DKD in the study population (area under the curve = 0.724, P < 0.05). The duration of diabetes correlated positively with uPCR and negatively with estimated glomerular-filtration rate. Neutrophil-Lymphocyte ratio was elevated in participants with DKD. This well-established marker of systemic inflammation exhibited significant positive association with CHIT-1. Conclusion: Plasma CHIT-1 protein is elevated in DKD and associated with disease progression. It is capable of reflecting disease severity and is closely related to systemic inflammation possibly caused by pro-inflammatory circulatory immune cells. [ABSTRACT FROM AUTHOR]

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation. [ABSTRACT FROM AUTHOR]

ApoB is the main protein of triglyceride-rich lipoproteins and is further divided into ApoB48 in the intestine and ApoB100 in the liver. Very low-density lipoprotein (VLDL) is produced by the liver, contains ApoB100, and is metabolized into its remnants, intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL). ApoB100 has been suggested to play a crucial role in the formation of the atherogenic plaque. Apart from being a biomarker of atherosclerosis, ApoB100 seems to be implicated in the inflammatory process of atherosclerosis per se. In this review, we will focus on the structure, the metabolism, and the function of ApoB100, as well as its role as a predictor biomarker of cardiovascular risk. Moreover, we will elaborate upon the molecular mechanisms regarding the pathophysiology of atherosclerosis, and we will discuss the disorders associated with the APOB gene mutations, and the potential role of various drugs as therapeutic targets.

An unbalanced diet increases the risk of developing a variety of chronic diseases and cancers, leading to higher morbidity and mortality rates worldwide. Low-grade systemic chronic inflammation mediated by the activation of the innate immune system is common to all these pathologies. Inflammation is a biological response of the body and a normal part of host defense to combat the effects of bacteria, viruses, toxins and macronutrients. However, when the innate immune system is constantly activated, it can promote the development of low-grade systemic chronic inflammation, which could play an important role in the development of chronic diseases and cancer. Since most chronic inflammatory diseases are associated with diet, a balanced healthy diet high in anti-inflammatory food components could prevent chronic diseases and cancer. The cells of the body’s immune system produce chemokines and cytokines which can have pro-inflammatory and tumor-promoting as well as anti-inflammatory and tumor-fighting functions. A challenge in the future will be to assess whether polymorphisms in immune-related genes may play a role in promoting pro-inflammatory activity. Thanks to this duality, future research on immune regulation could focus on how innate immune cells can be modified to convert a pro-inflammatory and tumor-friendly microenvironment into an anti-inflammatory and anti-tumor one. This review describes inflammatory responses mediated by the innate immune system in various diseases such as hyperglycemia and/or hyperlipemia, obesity, type II diabetes, cardiovascular disease and cancer.

One of the adverse outcomes of acute inflammatory response is progressing to the chronic stage or transforming into an aggressive process, which can develop rapidly and result in the multiple organ dysfunction syndrome. The leading role in this process is played by the Systemic Inflammatory Response that is accompanied by the production of pro- and anti-inflammatory cytokines, acute phase proteins, and reactive oxygen and nitrogen species.The purpose of this review that highlights both the recent reports and the results of the authors' own research is to encourage scientists to develop new approaches to the differentiated therapy of various SIR manifestations (low- and high-grade systemic inflammatory response phenotypes) by modulating redox-sensitive transcription factors with polyphenols and to evaluate the saturation of the pharmaceutical market with appropriate dosage forms tailored for targeted delivery of these compounds.Redox-sensitive transcription factors such as NFκB, STAT3, AP1 and Nrf2 have a leading role in mechanisms of the formation of low- and high-grade systemic inflammatory phenotypes as variants of SIR. These phenotypic variants underlie the pathogenesis of the most dangerous diseases of internal organs, endocrine and nervous systems, surgical pathologies, and post-traumatic disorders.The use of individual chemical compounds of the class of polyphenols, or their combinations can be an effective technology in the therapy of SIR. Administering natural polyphenols in oral dosage forms is very beneficial in the therapy and management of the number of diseases accompanied with low-grade systemic inflammatory phenotype. The therapy of diseases associated with high-grade systemic inflammatory phenotype requires medicinal phenol preparations manufactured for parenteral administration.

Abstract Background Elderly often show reduced immune functioning and can develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with altered cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65–74 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Presence of chronic low-grade inflammation was investigated by evaluating 18 different plasma inflammatory markers that had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and women, indicative of dysfunctional pSTAT responses in frailer individuals. Associations differed between men and women, with frailer women showing lower pSTAT1 responses in monocytes and frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells. Notably, lower IL-10-induced pSTAT3 responses in men were related to both higher frailty scores and higher CRP levels over the past 20 years. This might indicate poor resolution of low-grade inflammation due to defective regulatory pSTAT signaling in older men. Conclusions Our results emphasize the importance of preserved JAK-STAT pathway signaling in healthy aging and reveal cellular pSTAT levels as a candidate biomarker of frailty.

Introduction: The diseases number with a known inflammatory etiology is constantly increasing. Cardiovascular and neurodegenerative diseases, osteoporosis, cancer, asthma, atherosclerosis, type 2 diabetes and obesity are associated with chronic low-grade inflammation. There is evidence that individuals who engage in intense physical activity or who exercise regularly, shows changes in biomarkers associated with chronic inflammation. Physical exercise is useful in preventing many diseases, due to improved cardiorespiratory, metabolic, musculoskeletal function. All these improve the immunity and antioxidant capacity, thus reducing the incidence of acute and chronic inflammatory diseases. Materials and Methods: In this study were included 90 bibliographic sources, of which the title contains the following keywords: exercise - 23, inflammation - 27, anti-inflammatory - 6, IL-6 - 13, IL-10 - 4, myokine - 3, IL-15 - 3, irisin - 6, obesity - 11, chronic inflammation - 7. This study discussed aspects of exercise, pro- and anti-inflammatory cytokines, immunological mechanisms, the dual role of IL-6 cytokine, and the anti-inflammatory effects of physical exercise. Results: Physical exercise is an efficient clinical tool, that limits chronic inflammation activating the immune system that will increase the level of anti-inflammatory IL-6 myokine. There is a direct relationship between the volume and intensity of exercise and the amount of IL-6 myokine in the blood stream. Conclusions: These studies contribute significantly to the understanding of the mechanisms of the anti-inflammatory effect of exercise. More studies on chronic low-grade inflammatory diseases are needed to understand their pathophysiology, and that will inspire the specialists improve long-term treatment strategies.

Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6–20% of females in reproductive age. Most symptoms of PCOS arise early during puberty. Since PCOS involves a combination of signs and symptoms, thus it is considered as a heterogeneous disorderliness. The most accepted diagnostic criteria is Rotterdam criteria which involves two of the latter three features: (a) hyperandrogenism, (b) oligo- or an-ovulation, and (c) polycystic ovaries. The persistent hormonal imbalance leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females. Insulin resistance, cardiovascular diseases, abdominal obesity, psychological disorders, infertility, and cancer are also related to PCOS. These pathophysiologies associated with PCOS are interrelated with each other. Hyperandrogenism causes insulin resistance and hyperglycemia, leading to ROS formation, oxidative stress, and abdominal adiposity. In consequence, inflammation, ROS production, insulin resistance, and hyperandrogenemia also increase. Elevation of AGEs in the body either produced endogenously or consumed from diet exaggerates PCOS symptoms and is also related to ovarian dysfunction. This review summarizes how AGE formation, inflammation, and oxidative stress are significantly essential in PCOS progression. Alterations during prenatal development like exposure to excess AMH, androgens, or toxins (bisphenol-A, endocrine disruptors, etc.) may also be the etiologic mechanism behind PCOS. Although the etiology of this disorder is unclear, environmental and genetic factors are primarily involved. Physical inactivity, as well as unhealthy eating habits, has a vital role in the progression of PCOS. This review outlines a collection of specific genes phenotypically linked with PCOS. Furthermore, beneficial effect of metformin in maintaining endocrine abnormalities and ovarian function is also mentioned. Kisspeptin is a protein which helps in onset of puberty and increases GnRH pulsatile release during ovulation as well as role of KNDy neurons in GnRH pulsatile signal required for reproduction are also elaborated. This review also focuses on the immunology related to PCOS involving chronic low-grade inflammation, and how the alterations within the follicular microenvironment are intricated in the development of infertility in PCOS patients. How PCOS develops following antiepileptic and psychiatric medication is also expanded in this review. Initiation of antiandrogen treatment in early age (≤ 25 years) might be helpful in spontaneous conception in PCOS women. The role of BMP (bone morphogenetic proteins) in folliculogenesis and their expression in oocytes and granulosa cells are also explained. GDF8 and SERPINE1 expression in PCOS is given in detail. [ABSTRACT FROM AUTHOR]

Chronic inflammatory diseases, such as rheumatoid arthritis, steatohepatitis, periodontitis, chronic kidney disease, and others are associated with an increased risk of atherosclerotic cardiovascular disease, which persists even after accounting for traditional cardiac risk factors. The common factor linking these diseases to accelerated atherosclerosis is chronic systemic low-grade inflammation triggering changes in lipoprotein structure and metabolism. HDL, an independent marker of cardiovascular risk, is a lipoprotein particle with numerous important anti-atherogenic properties. Besides the essential role in reverse cholesterol transport, HDL possesses antioxidative, anti-inflammatory, antiapoptotic, and antithrombotic properties. Inflammation and inflammation-associated pathologies can cause modifications in HDL's proteome and lipidome, transforming HDL from atheroprotective into a pro-atherosclerotic lipoprotein. Therefore, a simple increase in HDL concentration in patients with inflammatory diseases has not led to the desired anti-atherogenic outcome. In this review, the functions of individual protein components of HDL, rendering them either anti-inflammatory or pro-inflammatory are described in detail. Alterations of HDL proteome (such as replacing atheroprotective proteins by pro-inflammatory proteins, or posttranslational modifications) in patients with chronic inflammatory diseases and their impact on cardiovascular health are discussed. Finally, molecular, and clinical aspects of HDL-targeted therapies, including those used in therapeutical practice, drugs in clinical trials, and experimental drugs are comprehensively summarised. [ABSTRACT FROM AUTHOR]

Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0–73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Chronic low-grade inflammation has been identified as a key pathway linking stress experience to human health. However, systematic evaluations on the relationship of work stress and immune function are scarce and predominantly based on cross-sectional studies. We performed a systematic review and meta-analysis of prospective studies on associations of working conditions and inflammatory biomarkers. METHODS: In line with our previously established study protocol and the PRISMA-guidelines, we systematically searched electronic databases for prospective studies on working conditions as well as workplace interventions and inflammatory markers in employees. We classified studies (by design, type of exposure/intervention, outcome) and performed rigorous risk-of-bias assessments. Studies were summarized qualitatively, and a meta-analysis was conducted. RESULTS: We identified 23 eligible studies (N=16 432) with a broad scope of working conditions and inflammatory markers. For interventional designs, we differentiated between individual-directed/behavioral (including physical and mental) and organization-directed/structural interventions. Workplace physical exercise interventions were associated with a decrease in C-reactive protein (k=5; d=-0.61; P

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a nonhomogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the proinflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology.

Managing chronic diseases, such as heart disease, stroke, diabetes, chronic lung disease and Alzheimer's disease, account for a large proportion of health care spending, yet they remain in the top causes of premature mortality and are preventable. It is currently accepted that an unhealthy lifestyle fosters a state of chronic low-grade inflammation that is linked to chronic disease progression. Although this is known to be related to inflammatory cytokines, how an unhealthy lifestyle causes cytokine release and how that in turn leads to chronic disease progression are not well known. This article presents a theory that an unhealthy lifestyle fosters chronic disease by changing interstitial cell behavior and is supported by a six-level hierarchical network analysis. The top three networks include the macroenvironment, social and cultural factors, and lifestyle itself. The fourth network includes the immune, autonomic and neuroendocrine systems and how they interact with lifestyle factors and with each other. The fifth network identifies the effects these systems have on the microenvironment and two types of interstitial cells: macrophages and fibroblasts. Depending on their behaviour, these cells can either help maintain and restore normal function or foster chronic disease progression. When macrophages and fibroblasts dysregulate, it leads to chronic low-grade inflammation, fibrosis, and eventually damage to parenchymal (organ-specific) cells. The sixth network considers how macrophages change phenotype. Thus, a pathway is identified through this hierarchical network to reveal how external factors and lifestyle affect interstitial cell behaviour. This theory can be tested and it needs to be tested because, if correct, it has profound implications. Not only does this theory explain how chronic low-grade inflammation causes chronic disease progression, it also provides insight into salutogenesis, or the process by which health is maintained and restored. Understanding low-grade inflammation as a stalled healing process offers a new strategy for chronic disease management. Rather than treating each chronic disease separately by a focus on parenchymal pathology, a salutogenic strategy of optimizing interstitial health could prevent and mitigate multiple chronic diseases simultaneously. [ABSTRACT FROM AUTHOR]

Qingsong Wang,1 Xiu-ling Zhou,2 Guang-hai Mei,3 Jiantao Wang,1 Zhongyu Yu,1 Yue Hu,1 Xinyu Guo,1 Hanyu Zhang,1 Xiaodie Xu,4 Chengfeng He,4 Jingchun Guo,4 Yinghong Tao,5 Houguang Zhou1 1Department of Geriatrics, Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Ultrasonics, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Key Laboratory of Medical Neurobiology, Institute of Brain Science, Fudan University, Shanghai, 200030, People’s Republic of China; 5Department of Medical Examination Center, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Houguang ZhouDepartment of Geriatrics of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, No. 24 Ward, Building 6, No.12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52887246Email zhouhouguang@huashan.org.cnYinghong TaoDepartment of Medical Examination Center of Huashan Hospital, Fudan University, Building 4, No. 12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52889087Email taoyinghong@huashan.org.cnAim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6).Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected.Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P< 0.05), and HDL-C levels were considerably reduced (P< 0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P< 0.05).Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.Keywords: metabolic inflammatory syndrome, MIS, heparanase, HPA, C-reactive protein, CRP, interleukin-6, IL-6, chronic low-grade inflammation, CLGI

Introduction Childhood maltreatment (CM) is one of the best described environmental risk factors for developing any psychiatric disorder, while it also confers increased odds for obesity, cardiometabolic disorders and all-cause mortality. Inflammation has been suggested to mediate the widespread clinical effects of CM. Previously, Ligthart et al. (2016) identified a polyepigenetic signature of circulating CRP levels, a measure of chronic low-grade inflammation, that has been reliably associated with a wide array of complex disorders. The study of this biomarker could dilucidate the mechanistic relationship between CM and psychiatric outcomes. Objectives Thus, CRP-associated epigenetic modifications were explored regarding proximal exposure to CM. Methods Genomic DNA was extracted from peripheral blood mononuclear cells of 157 children and adolescents (7 to 17 years old). Exposure to CM was assessed following the TASSCV criteria. Genome-wide DNA methylation was assessed by means of the EPIC array. Fifty-two out of the 58 original CRP-associated CpG sites surpassed quality control and were included in the analysis. Age, sex, psychopathological status and cell type proportions were included as covariates. Results DNA methylation at 12 out of 52 CpG sites (23%) was significantly associated with exposure to CM (p < .05); 8 of these associations survived correction for multiple testing (q < .05). Conclusions This is the first study to date to explore the relationship between childhood maltreatment and an epigenetic signature of chronic low-grade inflammation. Our findings underscore the presence of immune dysregulation early after exposure to CM; further studies are needed to assess the long-term clinical implications of this signature in psychiatric patients. Disclosure No significant relationships.

Jae-Min Park,1,2 Hye Sun Lee,3 Ju-Young Park,4 Dong-Hyuk Jung,5 Ji-Won Lee1 1Department of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea; 2Department of Medicine, Graduate School of Medicine, Yonsei University, Seoul, Republic of Korea; 3Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea; 4Department of Statistics and Data Science, Yonsei University, Seoul, Republic of Korea; 5Department of Family Medicine, Yonsei University College of Medicine, Yongin Severance Hospital, Gyeonggi-do, Republic of KoreaCorrespondence: Ji-Won LeeDepartment of Family Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of KoreaTel +82 2 2019 3482Fax +82 2 3462 8209Email indi5645@yuhs.acPurpose: Limited evidence is available on whether the white blood cell (WBC) count is a predictor of type 2 diabetes mellitus (T2DM) in non-obese individuals. This study aimed to determine whether WBC count could be used as an indicator for the prediction of incident T2DM among non-obese individuals using a large, community-based Korean cohort that was observed over 10 years.Patients and methods: A total of 4211 non-obese adults without diabetes aged 40– 69 years were selected from the Korean Genome and Epidemiology Study. The participants were divided into four groups according to WBC count quartiles. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident T2DM, based on the American Diabetes Association criteria, using multivariate Cox proportional hazards regression models over 10 years after the baseline survey.Results: During the follow-up period, 592 (14.1%) participants had newly developed T2DM. The higher quartile of WBC count groups showed significantly higher cumulative T2DM incidence over 10 years after the baseline survey (log-rank test, P < 0.001). Compared with the HRs for individuals in the referent lowest quartile, the HR (95% CI) for incident T2DM in individuals in the highest quartile was 1.55 (1.10– 2.18) after adjusting for confounding variables.Conclusion: A higher WBC count predicts future incident T2DM among community-dwelling non-obese Korean adults. This study suggests that WBC count could facilitate the prediction of non-obese individuals susceptible to T2DM.Keywords: white blood cell count, type 2 diabetes mellitus, chronic low-grade inflammation, non-obese adults

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.

Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting a mutual association between nutrition and female fertility. Different "fertile" dietary patterns have been studied; however, in humans, conflicting results or weak correlations are often reported, probably because of the individual variations in genome, proteome, metabolome, and microbiome and the extent of exposure to different environmental conditions. In this scenario, "precision nutrition", namely personalized dietary patterns based on deep phenotyping and on metabolomics, microbiome, and nutrigenetics of each case, might be more efficient for infertile patients than applying a generic nutritional approach. In this review, we report on new insights into the nutritional management of infertile patients, discussing the main nutrigenetic, nutrigenomic, and microbiomic aspects that should be investigated to achieve effective personalized nutritional interventions. Specifically, we will focus on the management of low-grade chronic inflammation, which is associated with several infertility-related diseases. [ABSTRACT FROM AUTHOR]

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity, and inflammation. In this study, we aimed at identifying the involvement of candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-α, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity. [ABSTRACT FROM AUTHOR]

Objective: The aim of this exploratory study was to investigate the development of low‐grade inflammation during ageing and its relationship with frailty. Methods: The trajectories of 18 inflammatory markers measured in blood samples, collected at 5‐year intervals over a period of 20 years from 144 individuals aged 65–75 years at the study endpoint, were related to the degree of frailty later in life. Results: IFN‐γ‐related markers and platelet activation markers were found to change in synchrony. Chronically elevated levels of IL‐6 pathway markers, such as CRP and sIL‐6R, were associated with more frailty, poorer lung function and reduced physical strength. Being overweight was a possible driver of these associations. More and stronger associations were detected in women, such as a relation between increasing sCD14 levels and frailty, indicating a possible role for monocyte overactivation. Multivariate prediction of frailty confirmed the main results, but predictive accuracy was low. Conclusion: In summary, we documented temporal changes in and between inflammatory markers in an ageing population over a period of 20 years, and related these to clinically relevant health outcomes. [ABSTRACT FROM AUTHOR]

Background: Elderly often show reduced immune functioning and can develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with altered cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65–74 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Presence of chronic low-grade inflammation was investigated by evaluating 18 different plasma inflammatory markers that had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results: We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and women, indicative of dysfunctional pSTAT responses in frailer individuals. Associations differed between men and women, with frailer women showing lower pSTAT1 responses in monocytes and frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells. Notably, lower IL-10-induced pSTAT3 responses in men were related to both higher frailty scores and higher CRP levels over the past 20 years. This might indicate poor resolution of low-grade inflammation due to defective regulatory pSTAT signaling in older men. Conclusions: Our results emphasize the importance of preserved JAK-STAT pathway signaling in healthy aging and reveal cellular pSTAT levels as a candidate biomarker of frailty. [ABSTRACT FROM AUTHOR]

Introduction: The diseases number with a known inflammatory etiology is constantly increasing. Cardiovascular and neurodegenerative diseases, osteoporosis, cancer, asthma, atherosclerosis, type 2 diabetes and obesity are associated with chronic low-grade inflammation. There is evidence that individuals who engage in intense physical activity or who exercise regularly, shows changes in biomarkers associated with chronic inflammation. Physical exercise is useful in preventing many diseases, due to improved cardiorespiratory, metabolic, musculoskeletal function. All these improve the immunity and antioxidant capacity, thus reducing the incidence of acute and chronic inflammatory diseases. Materials and Methods: In this study were included 90 bibliographic sources, of which the title contains the following keywords: exercise - 23, inflammation - 27, anti-inflammatory - 6, IL-6 - 13, IL-10 - 4, myokine - 3, IL-15 - 3, irisin - 6, obesity - 11, chronic inflammation - 7. This study discussed aspects of exercise, pro- and anti-inflammatory cytokines, immunological mechanisms, the dual role of IL-6 cytokine, and the anti-inflammatory effects of physical exercise. Results: Physical exercise is an efficient clinical tool, that limits chronic inflammation activating the immune system that will increase the level of anti-inflammatory IL-6 myokine. There is a direct relationship between the volume and intensity of exercise and the amount of IL-6 myokine in the blood stream. Conclusions: These studies contribute significantly to the understanding of the mechanisms of the anti-inflammatory effect of exercise. More studies on chronic low-grade inflammatory diseases are needed to understand their pathophysiology, and that will inspire the specialists improve long-term treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M1-like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has excellent anti-inflammatory activities and may be used in the treatment of a variety of inflammatory diseases. In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods Newborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively. Results The obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p

The purpose of the research is to investigate links between body mass index and changes in the leucocyte formula of peripheral blood in rats of different ages in experimental modeling of nongenetic alimentary obesity with subsequent MS development; to identify possible associations between these indicators in animals depending on age.Contingent and research methods. Metabolic syndrome was reproduced according to the developed method in rats of different age groups by combining high-fat and high-carbohydrate diet in parallel with pharmacological correction of physiological satiation inhibition.Results. It is determined that the mechanisms of low gradient chronic inflammation development in adipose tissues on the background of metabolic syndrome differ from classical inflammatory response mechanisms. Weight gain is associated with the activation of various leucocyte forms depending on age and degree of mass increase. Young rats have body mass index associated with the amount of peripheral blood neutrophils and more delayed in time; adult animals have body mass index associated with eosinophils, starting from the first month of metabolic syndrome development; old animals have body mass index associated with monocytes and lymphocytes, during the whole period of the trial. The dependence of inflammatory reaction symptoms on the age and sex of the animal on the background of obesity is confirmed by the present associative links (peripheral blood cell composition – animal’s age - body mass index) and can be determined later, as a marker factor for metabolic syndrome development.

Summary: Background: The hematopoietic stem cell disorders, myeloproliferative neoplasms (MPNs), are characterised by chronic low-grade inflammation (CLI). Recently, we showed that patients with MPNs have an increased prevalence of drusen and age-related macular degeneration (AMD), and drusen prevalence seemed associated with higher CLI. Studying MPNs may reveal more about drusen pathophysiology. This study investigated CLI further by measuring cytokine levels and complement system markers, comparing these between patients with MPNs and AMD. Methods: This cross-sectional study, between July 2018 and November 2020 conducted at Zealand University Hospital (ZUH) – Roskilde, Denmark, included 29 patients with neovascular AMD (nAMD), 28 with intermediate-stage AMD (iAMD), 62 with MPNs (35 with drusen - MPNd and 27 with healthy retinas - MPNn). With flow cytometry, we measured complement-regulatory-proteins (Cregs). With immunoassays, we investigated cytokine levels combined into a summary-inflammation-score (SIS). Findings: The MPNd and nAMD groups had similar SIS, significantly higher than the MPNn and iAMD groups. Additionally, we found SIS to increase over the MPN biological continuum from early cancer stage, essential thrombocytaemia (ET), over polycythaemia vera (PV) to the late-stage primary myelofibrosis (PMF). MPNs showed signs of complement dysregulation, with Cregs expression lower in PV than ET and PMF and even lower in PV patients with drusen. Interpretation: This study suggests that MPNd have a higher CLI than MPNn and may indicate systemic CLI to play a greater part in, and even initiate drusen formation. We suggest using MPNs as a “Human Inflammation Model” of drusen development. The CLI in MPNs elicits drusen formation, triggering more CLI creating a vicious cycle, increasing the risk of developing AMD. Funding: Fight for Sight, Denmark, and Region Zealand's research promotion fund.

Abstract Objective The aim of this exploratory study was to investigate the development of low‐grade inflammation during ageing and its relationship with frailty. Methods The trajectories of 18 inflammatory markers measured in blood samples, collected at 5‐year intervals over a period of 20 years from 144 individuals aged 65–75 years at the study endpoint, were related to the degree of frailty later in life. Results IFN‐γ‐related markers and platelet activation markers were found to change in synchrony. Chronically elevated levels of IL‐6 pathway markers, such as CRP and sIL‐6R, were associated with more frailty, poorer lung function and reduced physical strength. Being overweight was a possible driver of these associations. More and stronger associations were detected in women, such as a relation between increasing sCD14 levels and frailty, indicating a possible role for monocyte overactivation. Multivariate prediction of frailty confirmed the main results, but predictive accuracy was low. Conclusion In summary, we documented temporal changes in and between inflammatory markers in an ageing population over a period of 20 years, and related these to clinically relevant health outcomes.

Chronic inflammatory diseases, such as rheumatoid arthritis, steatohepatitis, periodontitis, chronic kidney disease, and others are associated with an increased risk of atherosclerotic cardiovascular disease, which persists even after accounting for traditional cardiac risk factors. The common factor linking these diseases to accelerated atherosclerosis is chronic systemic low-grade inflammation triggering changes in lipoprotein structure and metabolism. HDL, an independent marker of cardiovascular risk, is a lipoprotein particle with numerous important anti-atherogenic properties. Besides the essential role in reverse cholesterol transport, HDL possesses antioxidative, anti-inflammatory, antiapoptotic, and antithrombotic properties. Inflammation and inflammation-associated pathologies can cause modifications in HDL’s proteome and lipidome, transforming HDL from atheroprotective into a pro-atherosclerotic lipoprotein. Therefore, a simple increase in HDL concentration in patients with inflammatory diseases has not led to the desired anti-atherogenic outcome. In this review, the functions of individual protein components of HDL, rendering them either anti-inflammatory or pro-inflammatory are described in detail. Alterations of HDL proteome (such as replacing atheroprotective proteins by pro-inflammatory proteins, or posttranslational modifications) in patients with chronic inflammatory diseases and their impact on cardiovascular health are discussed. Finally, molecular, and clinical aspects of HDL-targeted therapies, including those used in therapeutical practice, drugs in clinical trials, and experimental drugs are comprehensively summarised.

Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0–73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly.

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty.

Aim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6). Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected. Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P< 0.05), and HDL-C levels were considerably reduced (P< 0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P< 0.05). Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS. [ABSTRACT FROM AUTHOR]

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease-2019 (COVID-19) pandemic has led to a global health care crisis. Emerging research suggest an unanticipated impact of COVID-19 on mental and/or psychological health of both the general community and affected individuals. The fear of the COVID-19 epidemic and the consequent lockdown and economic crisis has led to globally increased psychological distress. The biological bases of immediate and new onset of psychiatric symptoms in individuals with COVID-19 are not yet known. COVID-19 infection may lead to activated immune-inflammatory pathways and a cytokine storm. Activated immune-inflammatory pathways, especially chronic low-grade inflammation, are associated with major psychiatric disorders in at least a subset of individuals. We propose that both the (sub)chronic inflammatory response and cytokine storm might crucially be involved in the immediate manifestation of neuropsychiatric symptoms in individuals with COVID-19 infection as well as heightened expression of psychiatric symptoms in COVID-19 infected individuals with prior psychiatric conditions. These events might expand concepts in psychoneuroimmunology, with the importance of chronic-low grade inflammation augmented by the cytokine storm hypothesis. Additionally, this might augment and refine diagnosis and prognostic management as well as treatment.