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Purpose: We explored the anti-inflammatory role of the DPP-4 inhibitor teneligliptin, using sitagliptin as comparator, in different in vitro models of low-grade inflammation (LGI), evaluating the hyperglycemia-induced endothelial inflammation, the macrophage polarization, and the endothelium–macrophage interaction. Methods: The effects of DPP-4 and its inhibitors on macrophage polarization were evaluated in THP-1 cells by measuring mRNA expression of M1-M2 markers. HUVEC cells were used to analyze the effects of DPP-4 inhibitors on endothelial inflammation under normal and high glucose conditions. To evaluate the link between eNO and M1-M2 polarization, HUVECs were transfected with eNOS siRNA and co-cultured with THP-1 cells. The effects of DPP-4 inhibitors on macrophage polarization and eNO content were evaluated in a co-culture model of differentiated THP-1 cells + HUVECs under normal glucose (NG), high glucose (HG) and high metabolic memory (HM) conditions. Results: DPP-4 regulated M1/M2 macrophage polarization. Teneligliptin reduced M1 and enhanced M2 macrophage phenotype under DPP-4 stimulation, and attenuated hyperglycemia-induced endothelial inflammation. In THP-1 cells co-cultured with eNOS depleted HUVECs, M1 markers were enhanced, while M2 reduced, indicating an important role of eNO in polarization to M2 phenotype. In the co-culture model with HUVECs exposed to HG and HM, teneligliptin reduced M1 and enhanced M2 population, by increasing eNO levels. The anti-inflammatory effects of sitagliptin were not observed in these LGI models. Conclusion: Teneligliptin, but not sitagliptin, has anti-inflammatory effects in the various LGI models, by promoting a switch from M1 toward M2 phenotype and by decreasing hyperglycaemia-induced endothelial inflammation, suggesting that effects for LGI are different among DPP-4 inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: This series of meta-analyses were aimed to elucidate the impact of hypothyroidism on low-grade systemic inflammation and oxidative stress assessed by C-reactive protein (CRP) and malondialdehyde (MDA) respectively; and to evaluate the effect of levothyroxine replacement therapy (LRT) on those outcomes. Methods: PubMed database and the key studies references were searched prior to March 3, 2020. Data on serum or plasma CRP and MDA levels in SHT (subclinical) and/or OHT (overt) hypothyroid patients and controls were extracted to compute overall standardized mean differences (SMD) by the random-effects model. Results: A total of 93 studies were entered into analyses and ten main meta-analyses were performed. OHT (SMD = 0.72 [0.39; 1.04], k = 35), SHT (SMD = 1.58 [0.78; 2.38], k = 56) and even mild SHT (TSH < 10 mU/L, SMD = 2.19 [0.02; 4.37], k = 13) proved to have a detrimental effect on CRP levels. LRT showed a favorable effect on CRP levels, particularly in OHT (SMD = −0.30 [−0.57; −0.02], k = 17). Increased levels of MDA were also found, especially in OHT (SMD = 2.49 [0.66; 4.31], k = 13). LRT may also improve MDA levels; however future studies would further validate the advantageous effect of LRT in hypothyroidism. Heterogeneity primarily originated from different study designs and geographic locations. Conclusion: Overall, these meta-analyses reveal that screening for hs-CRP and MDA in hypothyroid patients as simple biomarkers of low-grade systemic inflammation and oxidative stress may become a useful tool to identify those at increased risk who may benefit most from early interventions. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.

Background and Objectives: In women of reproductive age, leukocytosis is a risk factor that bridges low-grade chronic inflammation (metabolic inflammation), metabolic changes, and polycystic ovary syndrome (PCOS) and is a potential early predictor of PCOS. This study aims to explore the predictive role of quantitative changes in white blood cells (WBCs) and neutrophils in PCOS-associated metabolic changes. Materials and Methods: A total number of 176 blood samples were obtained from age-matched women of the reproductive period, comprising 88 PCOS cases and 88 healthy controls. Hematological, metabolic, and anthropometric indices and ultrasonic assessment were recorded. Results: Elevated levels of luteinizing hormone, testosterone, and lipid parameters except HDL-C levels, and the prevalence of metabolic syndrome in PCOS were statistically significant (p < 0.001). The neutrophil count and neutrophil–lymphocyte ratio (NLR) in PCOS patients were significantly higher (p < 0.001) than their counterparts. The predictive ability of the neutrophil count and neutrophil–lymphocyte ratio (NLR) for PCOS, and possibly its associating subclinical inflammation at optimum cut-off values for the neutrophil count and NLR of >46.62% (sensitivity 94.32% and specificity 74.42%) and >1.23 (sensitivity 71.59% and specificity 100%), respectively. With regard to the areas under the curve (AUC) and Youden indices, they constituted 0.922 and 0.697 for neutrophil count and 0.926 and 0.716 for NLR, respectively. The comparative ROC z-statistic value was 2.222 and a p = 0.026. The multiple linear regression analysis revealed no significant influence for hormonal and metabolic independent variables on the neutrophil count in PCOS cases, but, as can be expected, revealed a significant negative relationship with the other components of WBCs. Conclusion: In conclusion, relative neutrophilia and elevated NLR are potential cost-effective, sensitive, and specific predictors of PCOS that may also shed light on the mechanism of chronic low-grade inflammation that is characteristic of the disease.

Purpose: We evaluated the effectiveness of iron supplementation in relation to baseline iron and inflammatory status of pregnant women and their offspring in Sri Lanka. Methods: Apparently healthy women aged 18–36 years at < 12 weeks of gestation prior to receiving any supplementation were randomly recruited at the antenatal clinics. They received 60 mg of elemental iron in combined iron–folic acid pills from 12 weeks of gestation until delivery via the National Maternal Supplementation Programme. Serum ferritins (SF), hemoglobin and high-sensitive C-reactive protein (hs-CRP) were assessed. The women were grouped as iron sufficient-inflammation (+), iron sufficient-inflammation (−), iron deficient-inflammation (+) and iron deficient-inflammation (−) based on their baseline iron stores and low-grade inflammation (hs-CRP > 5 < 10 mg/L) at baseline and late pregnancy. Results: Despite supplementation, SF in the iron sufficient-inflammation (+) women reduced significantly (p = 0.037) to deficiency state (SF < 30 µg/L) at mid-pregnancy. Whereas no significant changes were noted in the SF in iron sufficient-inflammation (−) women (p > 0.05). They maintained their stores at sufficient state until delivery. The cord SF was higher (p < 0.001) in iron sufficient-inflammation (−) than the inflammation (+) women. 96.4% of the iron deficient women remained deficient until delivery regardless of their inflammatory state. Low-grade inflammation was higher (p < 0.001) in women with baseline BMI > 25 kg/m2. Whereas inflammation at late pregnancy was higher (p < 0.001) in women who gained weight in excess of the recommended, regardless of their baseline BMI. Conclusion: Iron status prior to supplementation and low-grade inflammation associated with BMI > 25 kg/m2 and excess weight gain during pregnancy appear to modulate the effectiveness of iron supplementation. [ABSTRACT FROM AUTHOR]

In the past, osteoarthrosis (OA) was considered as a non-inflammatory disease where the destruction of the hyaline cartilage is the leading cause of the functional disorders. The researches in this area had been focused mainly on the cartilage and the underlying bone. Today it is clear that OA is a pathological process that affects also the other structures of the joint apparatus (synovium, ligaments, joint capsule). Recent understandings define OA as a disease of the synovial joint with three main elements: cartilage loss, remodeling of the adjacent bone and concomitant low-grade inflammation, which has a major pathogenetic role in the joint damage. This is an aseptic type of inflammation, which is the result of the interaction between the immune system and the joint structures, leading to overproduction of cytokines and other pro-inflammatory molecules. Identifying the key participants in the low-grade inflammation will allow new therapeutic approaches to be established and give new abilities for slowing the progression of the destruction of the joints. [ABSTRACT FROM AUTHOR]

Higher levels of pro-inflammatory cytokines are consistently found in the serum of first episode psychosis (FEP) patients and this immune dysfunction could contribute to neural harm. On the other hand, lengthy periods of active psychosis during the early phases of the illness appear to be associated to worst functional outcome. We aim to explore the possible relationship between lengthy periods of active psychosis during early phases of the illness and the levels of pro-inflammatory cytokines. This is a prospective clinical study consisting of a 3-year clinical follow-up. We assessed the relation between the duration of active psychosis in patients with FEP and the serum levels of 21 cytokines at baseline and 3 months after initiating antipsychotic medication. We used the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. The sample consisted of 59 patients with a FEP. The percentage of variation of the serum levels of the chemokine MIP-3α during the first 3 months of antipsychotic treatment and the score in negative psychotic symptoms 3 months after the initiation of antipsychotic medication, acted as predictors of the initial time to remission of positive psychotic symptoms. Our findings open the possibility to investigating the potential use of the variation in chemokine MIP-3α serum levels during the first months of antipsychotic treatment to identify a subtype of FEP patients that could benefit from an add-on treatment with immune modulators. NCT02897167. September 13, 2016. "Study of the Activation of Proinflammatory Pathways of Toll-like Receptors in Schizophrenia Patients (PAFIP_TLR)". https://clinicaltrials.gov/ct2/show/NCT02897167. • The variation in chemokine MIP-3α serum levels predicted the time to remission in patients with a first episode of psychosis. • The score in negative psychotic symptoms also predicted the time to remission in patients with a first episode of psychosis. • MIP-3α levels could identify a subtype of psychotic patients that could benefit from an add-on immune modulating treatment. [ABSTRACT FROM AUTHOR]

The product of Aoc3 gene is known as vascular adhesion protein-1 (VAP-1), a glycoprotein contributing to leukocyte extravasation and exhibiting semicarbazide-sensitive amine oxidase activity (SSAO). Regarding the immune functions of VAP-1/SSAO, it is known that mice bearing Aoc3 gene knock-out (AOC3KO) exhibit defects in leukocyte migration similar to those of mice expressing a mutated VAP-1 lacking functional SSAO activity (knock-in, AOC3KI). However, it has not been reported whether these models differ regarding other disturbances. Thus, we further compared endocrine-metabolic phenotypes of AOC3KO and AOC3KI mice to their respective control. Special attention was paid on adiposity, glucose and lipid handling, since VAP-1/SSAO is highly expressed in adipose tissue (AT). In both mouse lines, no tissue SSAO activity was found, while Aoc3 mRNA was absent in AOC3KO only. Although food consumption was unchanged, both AOC3KO and AOC3KI mice were heavier and fatter than their respective controls. Other alterations commonly found in adipocytes from both lines were loss of benzylamine insulin-like action with unchanged insulin lipogenic responsiveness and adiponectin expression. A similar downregulation of inflammatory markers (CD45, IL6) was found in AT. Glucose handling and liver mass remained unchanged, while circulating lipid profile was distinctly altered, with increased cholesterol in AOC3KO only. These results suggest that the lack of oxidase activity found in AOC3KI is sufficient to reproduce the metabolic disturbances observed in AOC3KO mice, save those related with cholesterol transport. Modulation of SSAO activity therefore constitutes a potential target for the treatment of cardiometabolic diseases, especially obesity when complicated by low-grade inflammation. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: To investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA)., Design: In this population-based retrospective cohort study, patients who were aged ≥40 years were newly initiated on statin therapy between 2002 and 2011, and had a statin prescription for ≥90 days in the first year of treatment were identified from the 2000 Longitudinal Generation Tracking Database. All patients were separated into groups with higher cDDD/y (>120 cDDD/y) and lower cDDD/y (≤120 cDDD/y; as an active comparator) values. Propensity score matching was performed to balance potential confounders. All recruited patients were followed up for 8 years. Marginal Cox proportional hazard models were used to estimate time-to-event outcomes of OA., Results: Compared with lower cDDD/y use, higher cDDD/y use did not reduce the risk of any joint OA (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.14). Dose-related analysis did not reveal any dose-dependent association. A series of sensitivity analyses showed similar results. Joint-specific analyses revealed that statin did not reduce the incidence of knee, hand, hip, and weight-bearing (knee or hip) OA., Conclusions: Higher cDDD/y statin use did not reduce the risk of OA in this Taiwanese nationwide cohort study. The complexity of OA pathogenesis might contribute to the ineffectiveness of statin. Repurposing statin with its anti-inflammation properties might be ineffective for OA development, and balancing the catabolism and anabolism of cartilage might be a major strategy for OA prevention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Growing evidence implicates systemic inflammation in the loss of structural brain integrity in natural ageing and disorder development. Chronic stress and glucocorticoid exposure can potentiate inflammatory processes and may also be linked to neuronal atrophy, particularly in the hippocampus and the human neocortex. To improve understanding of emerging maladaptive interactions between stress and inflammation, this study examined evidence for glucocorticoid- and inflammation-mediated neurodegeneration in healthy mid-aged adults. N = 169 healthy adults (mean age = 39.4, 64.5% female) were sampled from the general population in the context of the ReSource Project. Stress, inflammation and neuronal atrophy were quantified using physiological indices of chronic stress (hair cortisol (HCC) and cortisone (HEC) concentration), systemic inflammation (interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP)), the systemic inflammation index (SII), hippocampal volume (HCV) and cortical thickness (CT) in regions of interest. Structural equation models were used to examine evidence for pathways from stress and inflammation to neuronal atrophy. Model fit indices indicated good representation of stress, inflammation, and neurological data through the constructed models (CT model: robust RMSEA = 0.041, robust χ 2  = 910.90; HCV model: robust RMSEA <0.001, robust χ 2  = 40.95). Among inflammatory indices, only the SII was positively associated with hair cortisol as one indicator of chronic stress (β = 0.18, p < 0.05). Direct and indirect pathways from chronic stress and systemic inflammation to cortical thickness or hippocampal volume were non-significant. In exploratory analysis, the SII was inversely related to mean cortical thickness. Our results emphasize the importance of considering the multidimensionality of systemic inflammation and chronic stress, with various indicators that may represent different aspects of the systemic reaction. We conclude that inflammation and glucocorticoid-mediated neurodegeneration indicated by IL-6 and hs-CRP and HCC and HEC may only emerge during advanced ageing and disorder processes, still the SII could be a promising candidate for detecting associations between inflammation and neurodegeneration in younger and healthy samples. Future work should examine these pathways in prospective longitudinal designs, for which the present investigation serves as a baseline., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: In the domain of functional gastrointestinal disorders, Functional Dyspepsia (FD) stands out due to its widespread occurrence internationally. Historically, electroacupuncture (EA) has been employed as a therapeutic modality for FD, demonstrating notable clinical efficacy., Objectives: This research aimed to delve into the impact of EA on stress responses, minor duodenal inflammatory processes, and the integrity of the intestinal barrier within FD-affected rodent models while also elucidating the underlying mechanisms., Methods: Thirty-six male Wistar rats were evenly distributed into three cohorts: a normal, a modeled FD, and an EA treatment group. The FD condition in the rats, barring those in the normal, was induced through a series of multifactorial procedures. For the EA cohort, the rats received electroacupuncture at the acupoints RN12 (Zhongwan) and ST36 (Zusanli) for 20 minutes daily over a span of one week. The gastric residue rate (GRR), intestinal propulsion rate (IPR), and changes in emotional state were measured in each group of rats. Additionally, serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) were detected, and the duodenal inflammatory condition and intestinal mucosal barrier status were observed through staining and fluorescence. The expression levels of Claudin-1, Junctional Adhesion Molecule 1 (JAM-1), Corticotropin-Releasing Factor (CRF), and Corticotropin-Releasing Factor Receptor 1 (CRF-R1) were also detected., Results: The study demonstrated that EA had a positive effect on body weight and food intake, GRR, and IPR in FD rats. Additionally, the EA group showed a decrease in serum levels of CRH, ACTH, and CORT, as well as a decrease in the number of duodenal mast cells and tryptase content. Furthermore, the expression of tight junction proteins Claudin-1 and JAM-1 was increased in the EA group compared to the model group. EA also reduced the levels of CRF and CRF-R1 in the hypothalamus and duodenum., Conclusion: EA has been shown to improve the stress state of FD rats, inhibit the activation of mast cells in the duodenum, and reduce low-grade inflammatory response and damage to the intestinal mucosal barrier. It is believed that EA achieves these effects by modulating the expression of CRF and its receptors in the brain-gut interaction pathway through the CRF signaling pathway. This provides a new approach to treating FD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children., Competing Interests: Disclosures: Valmore Bermúdez, María José Calvo, Heliana Parra, Raquel Santeliz, Jordan Bautista, Eliana Luzardo, Nelson Villasmil, María Sofía Martínez, Maricamen Chacín, Clímaco Cano, Ana Checa-Ros and Luis D'Marco have no financial or nonfinancial relationships or activities to declare in relation to this article., (© Touch Medical Media 2023.)

BackgroundNeurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP.MethodWe analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses.ResultsIn primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations.ConclusionsThis study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our findings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP.

Obesity is one of the major health burdens of the 21st century as it contributes to the growing prevalence of its related comorbidities, including insulin resistance and type 2 diabetes. Growing evidence suggests a critical role for overnutrition in the development of low-grade inflammation. Specifically, chronic inflammation in adipose tissue is considered a crucial risk factor for the development of insulin resistance and type 2 diabetes in obese individuals. The triggers for adipose tissue inflammation are still poorly defined. However, obesity-induced adipose tissue expansion provides a plethora of intrinsic signals (e.g., adipocyte death, hypoxia, and mechanical stress) capable of initiating the inflammatory response. Immune dysregulation in adipose tissue of obese subjects results in a chronic low-grade inflammation characterized by increased infiltration and activation of innate and adaptive immune cells. Macrophages are the most abundant innate immune cells infiltrating and accumulating into adipose tissue of obese individuals; they constitute up to 40% of all adipose tissue cells in obesity. In obesity, adipose tissue macrophages are polarized into pro-inflammatory M1 macrophages and secrete many pro-inflammatory cytokines capable of impairing insulin signaling, therefore promoting the progression of insulin resistance. Besides macrophages, many other immune cells (e.g., dendritic cells, mast cells, neutrophils, B cells, and T cells) reside in adipose tissue during obesity, playing a key role in the development of adipose tissue inflammation and insulin resistance. The association of obesity, adipose tissue inflammation, and metabolic diseases makes inflammatory pathways an appealing target for the treatment of obesity-related metabolic complications. In this review, we summarize the molecular mechanisms responsible for the obesity-induced adipose tissue inflammation and progression toward obesity-associated comorbidities and highlight the current therapeutic strategies.

Aim: to try to assess the effect of manual lymphatic drainage on the biochemical parameters and quality of life of patients with abnormal body mass index. The study included three women, average age 46 years (patient 1 with normal body weight as a control; patient 2: overweight; patient 3 with class 2 obesity). After qualification, physiotherapeutic interview and examination was carried out; the concentrations of glycosylated haemoglobin (HbA1c), C-peptide, high-sensitivity C-reactive protein (hsCRP), lipid profile, and quality of life were also examined. Additionally, in patients with abnormal body mass index, biochemical parameters were monitored for 3 months. Each patient underwent 10 manual lymphatic drainage (MLD) therapy sessions, three times a week for 30 min. In the overweight patient (patient 2), a decrease in the concentration of C-peptide, hsCRP and triglycerides was observed after the series of MLD therapy. An improvement in the quality of life, intestinal motility, and a reduction in the frequency of flatulence were also noted. Moreover, after the therapy, patient 2 reported better sleep and increased vitality. In contrast, in patient 3 (with grade 2 obesity), a decrease in triglyceride levels, but not other biomarkers, was detected after the series of MDL therapy. Additionally, in patient 3, an improvement in the quality of life, an improvement in intestinal peristalsis, and reduction of menstrual pain were observed after MLD therapy. For comparison, in a patient with a normal body weight as a control (patient 1), there were no changes in biochemical parameters or improvement in the quality of life after MLD therapy. Our preliminary research indicates improvement of the concentration C-peptide, lipid profile, a reduction in the inflammation, and improved quality of life in patients with abnormal body mass index after MLD therapy. However, more studies are needed to elucidate the effectiveness of MLD therapy in patients with varying degrees of abnormal body mass index, i.e., from overweight to obesity.

Abstract Background Although self-rated health (SRH) independently predicts mortality, the biological background of this association remains unexplained. This study aimed to examine the association between SRH and serum high-sensitivity C-reactive protein (hsCRP) level. Methods Subjects were 899 participants aged 35–69 years (237 men and 662 women) in the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. They were enrolled from 2008 to 2010. Of the subjects, 666 participated in a second survey 5 years later. Lifestyle factors and SRH were assessed using a self-administered questionnaire. Serum hsCRP level was measured using a latex-enhanced immunonephelometric assay. The association between SRH and serum hsCRP level was evaluated using a general linear model with covariates. We further longitudinally investigated whether higher serum hsCRP level at baseline predicts poor SRH after 5 years using an unconditional logistic regression model. Results A higher serum hsCRP level was significantly associated with poor SRH at baseline after adjusting for covariates (p for trend = 0.023). The age- and sex-adjusted odds ratio and 95% confidence interval (CI) for poor SRH after 5 years was 1.45 (95% CI: 0.76–2.78) for the highest tertile compared with the lowest tertile of serum hsCRP level at baseline with a significant linear trend (p for trend = 0.033), although the risk increase disappeared after adjustment for other covariates. Conclusions The present study demonstrated that poor SRH is cross-sectionally associated with higher serum hsCRP level. However, the longitudinal data did not support the relationship between serum hsCRP level at baseline and future SRH. Further longitudinal studies that include data on mortality and multiple inflammatory markers are warranted to elucidate the possible role of low-grade inflammation in the association between SRH and mortality risk.

Abstract Background Lack of vitamin D (VD) has been associated with colorectal cancer (CRC). VD has anti-inflammatory effects and regulates several cellular pathways by means of its receptor, including epigenetic modifications. Adipose tissue dysfunction has been related to low-grade inflammation, which is related to diseases like cancer. The aim of this study was to explore the relationship between serum 25-hydroxyvitamin D (25(OH)D), adipose tissue gene expression of VD receptor (VDR), pro-inflammatory markers, and the epigenetic factor DNA methyltransferase 3a (DNMT3A) as well as VDR promoter methylation in CRC. Methods Blood and visceral adipose tissue from 57 CRC and 50 healthy control subjects were collected. CRC subjects had lower serum 25(OH)D levels and higher VDR gene expression, and these were negatively correlated in the CRC group. Results Adipose tissue NFκB1, IL6, and IL1B gene expression were higher in the CRC subjects than in the control subjects. 25(OH)D correlated negatively with NFκB1 and CRP. In turn, CRP correlated positively with NFκB1, IL6, IL1B, and VDR gene expression as well as NFκB1 that correlated positively with IL6 and IL1B. DNMT3A mRNA was negatively correlated with serum 25(OH)D and positively correlated with VDR DNA methylation. VDR DNA methylation at position 4 had lower levels in the CRC group. Global NFκB1 methylation at dinucleotide 3 was lower in the CRC group. Conclusion Our results suggest that adipose tissue may be a key factor in CRC development. The low 25(OH)D levels and high adipose tissue VDR expression in CRC may, at least in part, mediate this relationship by modifying adipose tissue DNA methylation and promoting inflammation.

Abstract Background Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). Objectives The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. Methods This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. Results In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1β, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1β, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. Conclusions Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.

Abstract Background With ageing, long-standing inflammation can be destructive, contributing to development of several disorders, among these Alzheimer’s disease (AD). C-reactive protein (CRP) is a relatively stable peripheral inflammatory marker, but in previous studies the association between highly sensitive CRP (hsCRP) and AD have shown inconsistent results. This study examines the association between AD and hsCRP in blood samples taken up to 15 years prior to the diagnoses of 52 persons with AD amongst a total of 2150 persons ≥60 years of age. Results Data from Norway’s Nord-Trøndelag Health Study (HUNT 2) and the Health and Memory Study (HMS) were linked. The participants had an average age of 73 years, and diagnosed with AD up to 15 years [mean 8.0 (±3.9)] following hsCRP measurement. Logistic regression models showed an adverse association between hsCRP and AD in participants aged 60-70.5 (odds ratio: 2.37, 95% CI: 1.01-5.58). Conversely, in participants aged 70.6-94, there was an inverse association between hsCRP and AD (odds ratio: 0.39, 95% CI: 0.19-0.84). When applying multivariate models the findings were significant in individuals diagnosed 0.4-7 years after the hsCRP was measured; and attenuated when AD was diagnosed more than seven years following hsCRP measurement. Conclusions Our study is in line with previous studies indicating a shift in the association between hsCRP and AD by age: in adults (60-70.5 years) there is an adverse association, while in seniors (>70.6 years) there is an inverse association. If our findings can be replicated, a focus on why a more active peripheral immune response may have a protective role in individuals ≥70 years should be further examined.

The association between social relations and health outcomes is well described, but pathways are relatively poorly understood. Inflammation has been suggested as a potential physiological pathway, linking social relations to adverse health outcomes. However, previous studies have shown ambiguous results and have for the vast majority been based on studies small in sample size. The aim of the present study is to examine the association between comprehensive measures of structural and positive as well as negative functional aspects of social relations, across four relational domains—partner/spouse, children, other family and friends, and the level of systemic low-grade inflammation in a large population-based middle-aged cohort and to examine variation by gender and socioeconomic position in these associations. The study comprised of 5576 participants in the Copenhagen Aging and Midlife Biobank. The inflammatory biomarkers collected in late midlife included C-reactive protein, Interleukin-6, and TNF-alpha. Multiple linear regression models were implemented to explore associations between social relations and inflammatory measures controlling for gender, age, socioeconomic position, marital status, early major lifeevents and morbidity. Results show weak and ambiguous associations in all analyses. There were no strong indications of interaction with socioeconomic position. Concluding cautiously, men appear to be more vulnerable toward living alone and low contact frequency with family compared to women as regards high level of low-grade inflammation. In conclusion, this large-scale population-based study among middle-aged men and women showed no association between social relations and low-grade inflammation. [ABSTRACT FROM AUTHOR]

Background and Aims: Several cross-sectional, but few prospective, studies suggest that inflammation may be involved in the development of high blood pressure. We examined markers of inflammation for their associations with blood pressure levels over a two-year period in healthy adolescents.Methods and Results: The sample comprised 406 adolescents (209 girls) aged 12-18 years in the LabMed Physical Activity Study were followed-up for 2 years. Anthropometric (weigh, height, BMI), markers of inflammation (high sensitivity C-reactive protein, complement factors C3 and C4, fibrinogen, leptin and adiponectin) and ambulatory blood pressure (BP) were collected. Socioeconomic status, pubertal development, adherence to Mediterranean diet and cardiorespiratory fitness were measured for adjustment for potential confounders. Adjusted linear regression models revealed a significant association of Leptin/Adiponectin (L/A) Ratio (baseline) with systolic BP (β = 0.120; p < 0.034) and with diastolic BP (β = 0.125; p < 0.036) at follow-up (full adjusted model). Leptin was associated with systolic BP at follow-up (β = 0.102; p < 0.038) after adjustment for systolic BP at baseline, height, pubertal stage, socioeconomic status, adherence to Mediterranean diet, cardiorespiratory fitness, however, not independently of BMI.Conclusion: L/A ratio was positively associated with systolic BP and diastolic BP even after adjusting confounding variables. Therefore, a higher misbalance between leptin and adiponectin (higher L/A ratio) early adolescence may exert a negative effect BP levels in late adolescence regardless of several confounders factors. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim was to investigate whether an intensive lifestyle intervention, with high volumes of exercise, improves beta cell function and to explore the role of low-grade inflammation and body weight. Methods: This was a randomised, assessor-blinded, controlled trial. Ninety-eight individuals with type 2 diabetes (duration <10 years), BMI of 25–40 kg/m2, no use of insulin and taking fewer than three glucose-lowering medications were randomised (2:1) to either the standard care plus intensive lifestyle group or the standard care alone group. Standard care consisted of individual guidance on disease management, lifestyle advice and blinded regulation of medication following a pre-specified algorithm. The intensive lifestyle intervention consisted of aerobic exercise sessions that took place 5–6 times per week, combined with resistance exercise sessions 2–3 times per week, with a concomitant dietary intervention aiming for a BMI of 25 kg/m2. In this secondary analysis beta cell function was assessed from the 2 h OGTT-derived disposition index, which is defined as the product of the Matsuda and the insulinogenic indices. Results: At baseline, individuals were 54.8 years (SD 8.9), 47% women, type 2 diabetes duration 5 years (IQR 3–8) and HbA1c was 49.3 mmol/mol (SD 9.2); 6.7% (SD 0.8). The intensive lifestyle group showed 40% greater improvement in the disposition index compared with the standard care group (ratio of geometric mean change [RGM] 1.40 [95% CI 1.01, 1.94]) from baseline to 12 months' follow-up. Plasma concentration of IL-1 receptor antagonist (IL-1ra) decreased 30% more in the intensive lifestyle group compared with the standard care group (RGM 0.70 [95% CI 0.58, 0.85]). Statistical single mediation analysis estimated that the intervention effect on the change in IL-1ra and the change in body weight explained to a similar extent (59%) the variance in the intervention effect on the disposition index. Conclusions/interpretation: Our findings show that incorporating an intensive lifestyle intervention, with high volumes of exercise, in individuals with type 2 diabetes has the potential to improve beta cell function, associated with a decrease in low-grade inflammation and/or body weight. Trial registration: ClinicalTrials.gov NCT02417012 [ABSTRACT FROM AUTHOR]

Background: Psychological processes can be manifested in physiological health. We investigated whether acceptance and commitment therapy (ACT), targeted on psychological flexibility (PF), influences inflammation and stress biomarkers among working-age adults with psychological distress and overweight/obesity. Method: Participants were randomized into three parallel groups: (1) ACT-based face-to-face (n = 65; six group sessions led by a psychologist), (2) ACT-based mobile (n = 73; one group session and mobile app), and (3) control (n = 66; only the measurements). Systemic inflammation and stress markers were analyzed at baseline, at 10 weeks after the baseline (post-intervention), and at 36 weeks after the baseline (follow-up). General PF and weight-related PF were measured with questionnaires (Acceptance and Action Questionnaire, Acceptance and Action Questionnaire for Weight-Related Difficulties). Results: A group × time interaction (p =.012) was detected in the high-sensitivity C-reactive protein (hsCRP) level but not in other inflammation and stress biomarkers. hsCRP decreased significantly in the face-to-face group from week 0 to week 36, and at week 36, hsCRP was lower among the participants in the face-to-face group than in the mobile group (p =.035, post hoc test). Age and sex were stronger predictors of biomarker levels at follow-up than the post-intervention PF. Conclusion: The results suggest that ACT delivered in group sessions may exert beneficial effects on low-grade systemic inflammation. More research is needed on how to best apply psychological interventions for the health of both mind and body among people with overweight/obesity and psychological distress. Trial Registration: ClinicalTrials.gov Identifier: NCT01738256, Registered 17 August, 2012 [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with chronic low-grade inflammation, which has been linked to increased morbidity. However, inflammation variably and unpredictably improves after bariatric surgery. This study aimed at (1) evaluating the relationship between amplitude of weight loss and variation of inflammatory parameters after bariatric surgery, and (2) identifying, among clinical and biological baseline parameters, predictive factors of variation in inflammatory parameters. Methods: In a prospective cohort of patients who underwent bariatric surgery, serum concentrations of interleukin (IL)-6, IL-10, resistin, leptin, adiponectin chemerin, and C-reactive protein (CRP) were measured preoperatively and 1 year after surgery, and routine clinical and biochemical parameters were retrieved. Univariate and multivariate analyses (partial least square method) were performed to assess how parameters were associated with weight loss and to predict improvement of inflammatory parameters. Results: Eighty-seven patients were included (mean weight ± SD 136.3 ± 3.2 kg, 35 gastric bypasses, 52 sleeve gastrectomies). In parallel with weight loss (39.5 ± 13.8 kg), pro-inflammatory markers (IL-6, CRP, leptin, resistin) significantly decreased, and anti-inflammatory markers (IL-10, adiponectin) increased. Multivariate analysis revealed a significant association between weight loss and improvement in inflammatory parameters. Among all the clinical and biological preoperative parameters, baseline chemerin level was the only parameter that was significantly associated with global improvement of the inflammatory status after surgery. Conclusion: The amplitude of weight loss 1 year after bariatric surgery was strongly correlated with improvement of inflammatory profile, which could be predicted by baseline plasma level of chemerin. This suggests a key role of chemerin in obesity-driven inflammation, and a potential use as a biomarker. [ABSTRACT FROM AUTHOR]

Background: Neurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP. Method: We analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses. Results: In primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations. Conclusions: This study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our findings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP. [ABSTRACT FROM AUTHOR]

Aim: The purpose of the study is to research the serum TWEAK levels in obstructive sleep apnea syndrome (OSAS) patients. Material and Methods: Eighty-six subjects were admitted in the study, 59 being in the patient group and 27 in the control group. The patient group was further divided into subgroups of severe OSAS and mild-moderate OSAS. TWEAK levels between the groups were statistically compared. In addition, the correlation of sleep-related variables with TWEAK levels was investigated in the patient group. Results: TWEAK levels were lower in the patient group than in the control group. When the correlation between TWEAK levels and sleep-related variables are examined, inversely correlation between TWEAK levels and apnea-hypopnea index, the percentage of total sleep time spent with oxygen saturation below 90% and oxygen desaturation index was found. Conclusion: Serum TWEAK levels in OSAS patients and its relation with sleep variables showed for the first time that TWEAK may be a new inflammatory biomarker for OSAS. [ABSTRACT FROM AUTHOR]

Carbohydrate-restricted diets are increasingly recognized as options for dietary management of type 2 diabetes mellitus (T2DM). We investigated the effects of a carbohydrate-reduced high-protein (CRHP) and a conventional diabetes (CD) diet on oxidative stress and inflammation in weight stable individuals with T2DM. We hypothesized that the CRHP diet would improve markers of oxidatively generated RNA and DNA modifications as well as inflammatory parameters. Thirty participants with T2DM were randomized to 6 weeks of CRHP or CD dietary treatment (30/50 energy percentage (E%) carbohydrate, 30/17E% protein, 40/33E% fat), followed by a cross-over to the opposite diet for a subsequent 6-week period. All meals were provided during the study and body weight was controlled. Diurnal urine samples were collected after 4 weeks on each diet and oxidatively generated RNA and DNA modifications were measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), respectively. Fasting concentrations of soluble urokinase plasminogen activator receptor, high-sensitivity C-reactive protein, tumor necrosis factor alpha and interleukin-6 were measured before and after 6 weeks of interventions. Compared with the CD diet, the CRHP diet increased 24-hour urinary excretion of 8-oxoGuo by 9.3% (38.6 ± 12.6 vs. 35.3 ± 11.0 nmol/24 h, p =.03), whereas 8-oxodG did not differ between diets (24.0 ± 9.5 vs. 24.8 ± 11.1 nmol/24 h, p =.17). Changes in plasma inflammatory parameters did not differ between CRHP and CD diets, all p ≥.2. The clinical implications of increased RNA oxidation following a CRHP diet as well as long-term effects of carbohydrate-restriction on markers of oxidatively generated nucleic acid modifications should be a field of future study. [ABSTRACT FROM AUTHOR]

Background and Aims: Pediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish children, independent of degree of adiposity. We further assess the value of integrating multiple inflammation markers to identify children with very-high cardiometabolic risk profiles.Method and Results: We studied 2192 children and adolescents aged 6-18 years from an obesity clinic cohort and a population-based cohort, in a cross-sectional study design. Anthropometry, blood pressure, pubertal stage and body composition by dual-energy X-ray absorptiometry were assessed, and biomarkers including fasting serum high sensitivity C-reactive protein (hsCRP), white blood cells (WBC), resistin, lipid profile and glucose metabolism were measured. Adjusted correlation analysis and odds ratios were calculated. We found that, independent of degree of adiposity, having high-normal inflammation marker concentrations associated with increased cardiometabolic risk: for girls, hsCRP >0.57-9.98 mg/L (mid/upper tertile) associated with ~2-fold higher odds of dyslipidemia and hepatic steatosis (vs. lower tertile). For both sexes, WBC >7.0-12.4 109/L (upper tertile) associated with 2.5-fold higher odds of insulin resistance. Lastly, children with multiple inflammation markers in the high-normal range exhibited the most severe cardiometabolic risk profile.Conclusion: Low-grade inflammation associates with cardiometabolic risk in children independent of degree of adiposity. The associations vary with sex and inflammation marker measured. Finally, integrating multiple low-grade inflammation markers identifies a very-high-risk subgroup of children with overweight/obesity and may have clinical value. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.Methods: This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined.Results: In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p < 0.0001) and all IGFBP-1 phosphoisoforms (p < 0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain.Conclusions: Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.Trial Registration: The trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov ( NCT01240785 ) November 3, 2010. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to derive overall and sex-specific dietary patterns associated with inflammatory biomarkers in a general population sample from Northern Germany. Methods: The present analysis included 1158 participants (477 men, 681 women, mean age: 53.1 years; mean body mass index: 26.2 kg/m2) of the Food Chain Plus (FoCus) cohort in Kiel, Germany. Participants completed a semi-quantitative food frequency questionnaire and provided blood samples. Reduced rank regression with C-reactive protein (CRP) and Interleukin 6 (IL-6) as response variables was used to derive dietary patterns. After a mean follow-up of 1.7 years, a second blood sample was obtained in a subsample of 112 individuals. Multiple regression models were used to examine the association between dietary patterns at baseline and inflammatory biomarkers at follow-up. Results: The overall pattern characterised by high intakes of soft drinks, meat, potatoes and sauce, and low intakes of other cereals (except pasta/rice), wine, nuts, seeds, vegetarian dishes, vegetable oil, and fish was positively associated with CRP (OR 2.20; 95% CI 1.12, 4.35) and IL-6 (OR 3.14; 95% CI 1.26, 7.87) at follow-up. In men, the dietary pattern was higher in soft drinks, processed meat and low in cereals and plant-based fats. In women, the pattern was characterised by soft drinks, meat, vegetables and low in other cereals, wine, nuts, and seeds. The association between sex-specific patterns with inflammatory biomarkers was weaker for CRP. Conclusion: We identified dietary patterns positively associated with established biomarkers of chronic low-grade inflammation. [ABSTRACT FROM AUTHOR]

• SuPAR was a strong prognostic biomarker of non-cardiac mortality after STEMI. • The suPAR level was independent of sampling time < 12 h after revascularization. • SuPAR may identify patients in risk of non-cardiac mortality prior to discharge. Identification of patients at high risk of non-cardiac mortality following ST-segment elevation myocardial infarction (STEMI) could guide clinicians to identify patients who require attention due to serious non-cardiac conditions after the acute phase of STEMI. The purpose of this study was to evaluate if the non-specific and prognostic biomarker of inflammation and comorbidity, soluble urokinase receptor (suPAR), could predict non-cardiac mortality in a cohort of STEMI patients. SuPAR was measured in 1,190 STEMI patients who underwent primary percutaneous coronary intervention (pPCI). The primary endpoint was non-cardiac mortality, secondary endpoints were cardiac mortality, all-cause mortality, reinfarction and periprocedural acute kidney injury. Backwards elimination of potential confounders significantly associated with the respective outcome was used to adjust associations. Patients were followed for a median of 3.0 years (interquartile range 2.5– 3.6 years). Multivariate cox regression revealed that a plasma suPAR level above 3.70 ng mL−1 was associated with non-cardiac and cardiac mortality at hazard ratios 3.33 (95% confidence interval 1.67–6.63, p = 0.001, adjusted for age) and 0.99 (0.18–5.30, p = 0.98, adjusted for previous myocardial infarction and left ventricular ejection fraction), respectively. In patients with pPCI treated STEMI, suPAR was an independent prognostic biomarker of non-cardiac but not cardiac mortality and may identify patients with high risk of non-cardiac mortality. [ABSTRACT FROM AUTHOR]

Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease. In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4–10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses. Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (β-coefficient −0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (β-coefficients −0.25; 95%CI -0.33,-0.16 and −0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (β-coefficient −0.17; 95%CI -0.26,-0.07). Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease. Image 1 • In patients with established cardiovascular disease (CVD), lifestyle improvements are related to a decrease in C-reactive protein (CRP). • These lifestyle improvements are smoking cessation, physical activity increase, and weight loss. • Multiple lifestyle changes are related to the most decrease in CRP concentration. • Lifestyle changes might reduce CVD risk partly through lowering systemic inflammation. [ABSTRACT FROM AUTHOR]

Obesity is one of the major health burdens of the 21st century as it contributes to the growing prevalence of its related comorbidities, including insulin resistance and type 2 diabetes. Growing evidence suggests a critical role for overnutrition in the development of low-grade inflammation. Specifically, chronic inflammation in adipose tissue is considered a crucial risk factor for the development of insulin resistance and type 2 diabetes in obese individuals. The triggers for adipose tissue inflammation are still poorly defined. However, obesity-induced adipose tissue expansion provides a plethora of intrinsic signals (e.g., adipocyte death, hypoxia, and mechanical stress) capable of initiating the inflammatory response. Immune dysregulation in adipose tissue of obese subjects results in a chronic low-grade inflammation characterized by increased infiltration and activation of innate and adaptive immune cells. Macrophages are the most abundant innate immune cells infiltrating and accumulating into adipose tissue of obese individuals; they constitute up to 40% of all adipose tissue cells in obesity. In obesity, adipose tissue macrophages are polarized into pro-inflammatory M1 macrophages and secrete many pro-inflammatory cytokines capable of impairing insulin signaling, therefore promoting the progression of insulin resistance. Besides macrophages, many other immune cells (e.g., dendritic cells, mast cells, neutrophils, B cells, and T cells) reside in adipose tissue during obesity, playing a key role in the development of adipose tissue inflammation and insulin resistance. The association of obesity, adipose tissue inflammation, and metabolic diseases makes inflammatory pathways an appealing target for the treatment of obesity-related metabolic complications. In this review, we summarize the molecular mechanisms responsible for the obesity-induced adipose tissue inflammation and progression toward obesity-associated comorbidities and highlight the current therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective To investigate the characteristics of intestinal flora in patients with irritable bowel syndrome (IBS) and its relationship with the activation of mast cells (MC) in the intestinal mucosa. Methods The colon mucosa samples of 25 patients with IBS (IBS group) and 13 healthy subjects (control group) were collected, including 15 cases of diarrhea-predominant IBS (IBS-D group) and 10 cases of unsub typed IBS (IBS-U group). The intestinal flora and its abundance were detected by high-throughput sequencing platform, the species diversity of intestinal flora was evaluated by Alpha diversity analysis, the number and the activation of MC in intestinal mucosa (MC degranulation) were observed by toluene blue staining, and the relationship between intestinal flora and the activation of MC in IBS patients was analyzed Results At phylum level, among the intestinal mucosa flora in each group, the top three strains were Proteobacteria, Firmicutes, and Bacteroidtes; there was no significant difference in diversity index of intestinal flora. At genus level, the abundance of Granulicatella in IBS-D and IBS-U groups was lower than that of the control group, while the abundance of Tissierella in the IBS-D and IBS-U groups was higher than that of the control group (all P<0.05), the abundance of syntrophaceae, Porphyromonas, Marmoricola, Cardiobacterium in the IBS-D group was higher than that of the IBS-U group and the control group ( all P<0.05); there was no significant difference in MC count among different groups; the degranulation rates of MC in the IBS-D group and IBS-U group were higher than that of control group (all P <0.05), but there was no significant difference between IBS-D group and IBS-U group. In the IBS group, the MC degranulation rate of intestinal mucosa was not significantly correlated with the abundance of Granulicatella (r = 0.113,P >0.05), but was positively correlated with the abundance of Tissierella (r =0. 723,P<0.01) . Conclusions The intestinal flora of IBS patients mainly consist of Proteobacteria, Firmicutes, and Bacteroidtes, and there is no significant change in the diversity of intestinal flora. The abundance of some microbiota changes in patients with IBS, and the abundance of intestinal flora in different subtypes of JBS patients is different. The degranulation rate of intestinal mucosa mast cells in patients with JBS increases, and there is a certain correlation between the degranulation rate and the abundance of Tissierella. [ABSTRACT FROM AUTHOR]

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules. [ABSTRACT FROM AUTHOR]

Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, hormonal, and vascular mechanisms regulating blood pressure (BP), so crucial importance is given to the imbalance of a number of vasoactive factors produced by the endothelium. Decreased nitric oxide production and increased production of endothelin-1 (ET-1) in the vascular wall may promote oxidative stress and low-grade inflammation, with the development of endothelial dysfunction (ED) and increased vasoconstrictor activity. Increased ET-1 production can contribute to arterial aging and the development of atherosclerotic changes, which are associated with increased arterial stiffness and manifestation of isolated systolic HTN. In addition, ET-1 is involved in the complex regulation of BP through synergistic interactions with angiotensin II, regulates the production of catecholamines and sympathetic activity, affects renal hemodynamics and water–salt balance, and regulates baroreceptor activity and myocardial contractility. This review focuses on the relationship between ET-1 and HTN and in particular on the key role of ET-1 in the pathogenesis of ED, arterial structural changes, and impaired vascular regulation of BP. The information presented includes basic concepts on the role of ET-1 in the pathogenesis of HTN without going into detailed analyses, which allows it to be used by a wide range of specialists. Also, the main pathological processes and mechanisms are richly illustrated for better understanding.

Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male ZDF rats were used as a model of T2DM (35 diabetic ZDF‐Leprfa/fa and 16 ZDF-Lepr+/+ controls). Empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 6 weeks. Treatment with empagliflozin restored glycemic control. Empagliflozin improved endothelial function (thoracic aorta) and reduced oxidative stress in the aorta and in blood of diabetic rats. Inflammation and glucotoxicity (AGE/RAGE signaling) were epigenetically prevented by SGLT2i treatment (ChIP). Linear regression analysis revealed a significant inverse correlation of endothelial function with HbA1c, whereas leukocyte-dependent oxidative burst and C-reactive protein (CRP) were positively correlated with HbA1c. Viability of hyperglycemic endothelial cells was pleiotropically improved by SGLT2i. Empagliflozin reduces glucotoxicity and thereby prevents the development of endothelial dysfunction, reduces oxidative stress and exhibits anti-inflammatory effects in ZDF rats, despite persisting hyperlipidemia and hyperinsulinemia. Our preclinical observations provide insights into the mechanisms by which empagliflozin reduces cardiovascular mortality in humans (EMPA-REG trial).

Overweight and obesity are two of the most important public health problems in Mexico. There is a clear association between lifestyle and obesity. This relationship means that unhealthy lifestyles can modify people's physiological response through adipocytokines, proinflammatory factors which are closely related to chronic degenerative diseases. Obesity causes low-grade chronic inflammation. Adipose tissue, in addition to its function of storing energy reserves in the form of triglycerides, has important functions as an endocrine organ, producing a variety of molecules called adipocytokines such as IL-1, IL-6, IL-8, IFNγ, TNFα, leptin and resistin. The production of these molecules by adipocytes, coupled with the destruction of these cells, induces the inflammation to become chronic, and influences other systems by altering their functions, which leads to different diseases. Understanding the relationship between the different components of lifestyle and the production of adipocytokines involved in the development of chronic degenerative diseases, will allow us to address the problem and hence reduce the morbidity and mortality caused by these diseases.

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulinresistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0–7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32–31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01–0.25, P < 0.05) and 0.38 min (95% CI 0.09–0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.

Systemic low-grade inflammation can be initiated in vivo after traumatic injury or in chronic diseases such as neurodegenerative, metabolic, and autoimmune diseases. Inducers of inflammation trigger production of inflammatory mediators, which alter the functionality of tissues and organs and leads to harmful induction of different barrier systems in the body, where the blood-brain barrier, the blood-retinal barrier, blood-nerve barrier, blood-lymph barrier and the blood-cerebrospinal fluid barrier play major roles. The different barriers are unique but structured in a similar way. They are equipped with sophisticated junctional complexes where different connexins, protein subunits of gap junction channels and hemichannels, constitute important partners. The cells involved in the various barriers are coupled in networks, are excitable but do not express action potentials and may be targets for inflammation leading to changes in several biochemical cellular parameters. During any type of inflammation barrier break-down is observed where any form of injury can start with low-grade inflammation and may lead to systemic inflammation.

Obesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic and inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts metabolic and immune signaling leading to metabolic endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the gut barrier but also exert metabolic and immunomodulatory effects via G protein-coupled receptor binding and epigenetic regulation. SCFAs are emerging as potential agents to counteract dysbiosis-induced epigenetic changes, specifically targeting metabolic and inflammatory genes through DNA methylation, histone acetylation, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). To assess whether SCFAs can effectively interrupt the detrimental cascade of obesity and inflammation, this review aims to provide a comprehensive overview of the current evidence for their clinical application. The review emphasizes factors influencing SCFA production, the intricate connections between metabolism, the immune system, and the gut microbiome, and the epigenetic mechanisms regulated by SCFAs that impact metabolism and the immune system., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kopczyńska and Kowalczyk.)

Background: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis., Methods: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point., Results: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis., Conclusions: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP., Competing Interests: Declarations of interest None., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)