Low-grade Inflammatory Condition Research Articles

The Effect of Enteric-Derived Lipopolysaccharides on Obesity.

Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment.

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

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

Obesity and recurrent miscarriage: The interconnections between adipose tissue and the immune system.

Currently, obesity is considered a global public health problem. It is the main risk factor for noncommunicable diseases and reproductive complications, such as recurrent miscarriage (RM). RM affects approximately 1% of couples of reproductive age, and recent studies suggest that its prevalence is increasing. Immunological abnormalities may be responsible for a significant number of cases of unexplained RM. Obesity is recognized as a chronic low-grade inflammatory condition. The accumulation of fat in obese adipose tissue promotes changes in the local and systemic immune response. Adipokines, exosomes, micro-RNAs, lipids, and other factors released or secreted by adipose tissue are responsible for the interconnection between obesity and the immune system. Obesity-induced dysregulation of the innate and acquired immune response is also involved in the immunopathology of pregnancy loss in patients with unexplained RM. Therefore, understanding the communication pathways between maternal adipose tissue and the immune response in women living with obesity and RM is an important objective. Thus, diagnostic tools and new immunomodulatory therapies may be proposed for the management of patients with concurrent obesity and RM.

The Role of Oxidative Stress and Inflammation in Obesity and Its Impact on Cognitive Impairments-A Narrative Review.

Obesity is a chronic low-grade inflammatory condition that induces the generation of oxidative stress and inflammation. This oxidative stress and inflammation stimulate brain atrophy and some morphological changes in the brain that eventually result in cognitive impairments. However, there is no exact study that has summarized the role of oxidative stress and inflammation in obesity and its impact on cognitive impairments. Thus, the objective of this review is to recapitulate the current role of oxidative stress and inflammation in cognitive decline based on in vivo evidence. A comprehensive search was performed in Nature, Medline and Ovid, ScienceDirect, and PubMed, and the search was limited to the past 10 years of publication. From the search, we identified 27 articles to be further reviewed. The outcome of this study indicates that a greater amount of fat stored in individual adipocytes in obesity induces the formation of reactive oxygen species and inflammation. This will lead to the generation of oxidative stress, which may cause morphological changes in the brain, suppress the endogenous antioxidant system, and promote neuroinflammation and, eventually, neuronal apoptosis. This will impair the normal function of the brain and specific regions that are involved in learning, as well as memory. This shows that obesity has a strong positive correlation with cognitive impairments. Hence, this review summarizes the mechanism of oxidative stress and inflammation that induce memory loss based on animal model evidence. In conclusion, this review may serve as an insight into therapeutic development focusing on oxidative stress and inflammatory pathways to manage an obesity-induced cognitive decline in the future.

Fecal microbiota and inflammatory and antioxidant status of obese and lean dogs, and the effect of caloric restriction.

Obesity is the most common nutritional disease in dogs, and is generally managed by caloric restriction. Gut microbiota alteration could represent a predisposing factor for obesity development, which has been associated with a low-grade inflammatory condition and an impaired antioxidant status. Besides, weight loss has been shown to influence the gut microbiota composition and reduce the inflammatory response and oxidative stress. However, these insights in canine obesity have not been fully elucidated. The aim of this study was to assess the differences in serum and inflammatory parameters, antioxidant status, fecal microbiota and bacterial metabolites in 16 obese and 15 lean client-owned dogs and how these parameters in obese may be influenced by caloric restriction. First, for 30 days, all dogs received a high-protein, high-fiber diet in amounts to maintain their body weight; later, obese dogs were fed for 180 days the same diet in restricted amounts to promote weight loss. Before the introduction of the experimental diet (T0), small differences in fecal microbial populations were detected between obese and lean dogs, but bacterial diversity and main bacterial metabolites did not differ. The fecal Dysbiosis Index (DI) was within the reference range (< 0) in most of dogs of both groups. Compared to lean dogs, obese dogs showed higher serum concentrations of acute-phase proteins, total thyroxine (TT4), and antioxidant capacity. Compared to T0, dietary treatment affected the fecal microbiota of obese dogs, decreasing the abundance of Firmicutes and increasing Bacteroides spp. However, these changes did not significantly affect the DI. The caloric restriction failed to exert significative changes on a large scale on bacterial populations. Consequently, the DI, bacterial diversity indices and metabolites were unaffected in obese dogs. Caloric restriction was not associated with a reduction of inflammatory markers or an improvement of the antioxidant status, while an increase of TT4 has been observed. In summary, the present results underline that canine obesity is associated with chronic inflammation. This study highlights that changes on fecal microbiota of obese dogs induced by the characteristics of the diet should be differentiated from those that are the consequence of the reduced energy intake.

Urticaria and comorbidities

Urticaria is a mast cell (MC)-driven skin disease. Degranulation of these cells is triggered by the activation of several receptors on its surface. The activation of MC in chronic spontaneous urticaria (CSU) appears to be associated with an autoimmune etiology. Certain comorbidities such as autoimmunity, infections, allergy, emotional stress, and metabolic syndrome are frequently associated with chronic urticaria (CU). The objective of this review is to highlight the frequent association between CU and several comorbidities, which can lead to a worse prognosis for the underlying disease. We searched for original and review articles on CU and comorbidities in PUBMED, abstracts published in AAAAI and EAACI; all of them in English. Our review reinforced how CSU, being itself an autoimmune disease, is strongly linked to several other autoimmune diseases. Besides autoimmunity, emotional stress was considered another frequent comorbidity associated with CU and also a trigger factor for urticaria exacerbation. Some studies recently considered CU as a low-grade chronic inflammatory condition and may be associated with metabolic syndrome. In conclusion, CU is considered a heterogeneous disease with distinct clinical features. It is worth remembering that CU should not be considered just a skin disease and its complete control could minimize a worse clinical outcome.

Abstract 2121: Gene expression and functional characterization of obesity-induced MDSC to uncover the link between obesity and cancer risk

Abstract Strong epidemiologic evidence suggests that excess body weight gain is a major risk of at least 13 different types of cancers. One of the mechanisms explaining the increased cancer incidence in obese patients is associated with the chronic low-grade inflammatory condition. Myeloid cells including macrophages and Myeloid-derived suppressor cells (MDSC) are increased in advanced adiposity. Previous studies in mouse models have shown that obesity-induced MDSC play a protective role on metabolic control; however, in the presence of malignant cells, MDSC facilitates tumor growth and metastasis. Our data show that compared to non-obese individuals, patients with severe obesity (body mass index [BMI] &amp;gt; 40) have a significant increase of circulating granulocytic cells displaying a gene signature resembling tumor-MDSC. Intriguingly, obesity-induced MDSC lacked the potent immunosuppressive function; and therefore, we called them obesity-induced G-MDSC-like cells (Ob-MDSC). The mechanisms underlying the regulation of MDSC phenotype in obesity and obesity-related cancer are unclear. We found that LDL, one altered obesity-related factor, and LPS differentially impact the expression of several genes including the immunosuppressive MDSC markers, arginase-1 and iNOS, when comparing mouse bone marrow-derived MDSC from high-fat fed mice with low-fat fed mice. This finding indicates that the responsiveness of MDSC may be regulated by their long-lasting exposure to the obese microenvironment. Therefore, we propose that long-term adaptation of MDSC is induced by dysfunctional metabolic factors in obesity that modulate their response to subsequent triggers, such as signals derived by the tumor microenvironment (TMA) in the context of obesity-associated cancer. Our data from obese mice with Diethylnitrosamine (DEN)-induced hepatocellular carcinoma and genetically altered hepatic lipid and lipoprotein metabolism show an increased infiltration of G-MDSC associated with enhanced tissue chemokine signaling pathway, ECM remodeling/metastasis, inflammation, and epigenetic and transcriptional regulation. Together our data suggest that chronic exposure to an obesity-related environment establishes a phenotype prone to become pro-tumor MDSC. The identification of key regulators of the gene expression driving the immunosuppressive phenotype of MDSC in obesity is critical for the discovery of therapeutical targets to reduce the risk of obesity-associated cancers. Citation Format: Maria D. Sanchez-Pino, Ramesh Thylur Puttalingaiah, Jone Garai, Jovanny Zabaleta, Randall L. Mynatt, William Richardson, Augusto Ochoa. Gene expression and functional characterization of obesity-induced MDSC to uncover the link between obesity and cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2121.

Role of EPA in Inflammation: Mechanisms, Effects, and Clinical Relevance.

Many chronic inflammatory processes are linked with the continuous release of inflammatory mediators and the activation of harmful signal-transduction pathways that are able to facilitate disease progression. In this context atherosclerosis represents the most common pathological substrate of coronary heart disease, and the characterization of the disease as a chronic low-grade inflammatory condition is now validated. The biomarkers of inflammation associated with clinical cardiovascular risk support the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk. Several literature data highlight cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA). This PUFA lowers plasma triglyceride levels and has potential beneficial effects on atherosclerotic plaques. Preclinical studies reported that EPA reduces both pro-inflammatory cytokines and chemokines levels. Clinical studies in patients with coronary artery disease that receive pharmacological statin therapy suggest that EPA may decrease plaque vulnerability preventing plaque progression. This review aims to provide an overview of the links between inflammation and cardiovascular risk factors, importantly focusing on the role of diet, in particular examining the proposed role of EPA as well as the success or failure of standard pharmacological therapy for cardiovascular diseases.

Nitazoxanide Exerts Immunomodulatory Effects on Peripheral Blood Mononuclear Cells from Type 2 Diabetes Patients.

Background: Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D. Methods: Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR. Results: NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ. Conclusions: Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits.

Metabolic changes in female rats exposed to intrauterine hyperglycemia and postweaning consumption of high-fat diet†.

We evaluated the influence of the hyperglycemic intrauterine environment and postweaning consumption of a high-fat diet (HFD) on the glycemia, insulin, lipid, and immunological profile of rat offspring in adulthood. Female rats received citrate buffer (Control-C) or Streptozotocin (a beta cell-cytotoxic drug to induce diabetes-D) on postnatal day 5. In adulthood, these rats were mated to obtain female offspring, who were fed a standard diet (SD) or HFD from weaning to adulthood (n= 10 rats/group). OC/SD and OC/HFD represent female offspring of control mothers and received SD or HFD, respectively; OD/SD and OD/HFD represent female offspring of diabetic mothers and received SD or HFD, respectively. At adulthood, the oral glucose tolerance test (OGTT) was performed and, next, the rats were anesthetized and euthanized. Pancreas was collected and analyzed, and adipose tissue was weighted. Blood samples were collected to determine biochemical and immunological profiles. The food intake was lower in HFD-fed rats and visceral fat weight was increased in the OD/HFD group. OC/HFD, OD/SD, and OD/HFD groups presented glucose intolerance and lower insulin secretion during OGTT. An impaired pancreatic beta-cell function was shown in the adult offspring of diabetic rats, regardless of diet. Interleukin (IL)-6 and IL-10 concentrations were lower in the OD/HFD group and associated to a low-grade inflammatory condition. The fetal programming was responsible for impaired beta cell function in experimental animals. The association of maternal diabetes and postweaning HFD are responsible for greater glucose intolerance, impaired insulin secretion and immunological change.

COVID-19 Pandemi Sürecinde İdeal Vücut Ağırlığının Önemi

The Importance of Ideal Body Weight in the COVID-19 Pandemia Period Obesity is an important public health problem that is common worldwide. With obesity, there is an increase in many diseases, including hypertension, cardiovascular diseases and diabetes, which are risk factors for COVID-19. In 2009, obesity was first defined as a risk factor for disease severity and mortality in infected individuals in the pandemic caused by H1N1 Influenza A virus affecting the upper respiratory tract. Then, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which emerged in 2012, was also found to be more common in individuals with obesity. These findings, which show that obesity increases the risk of disease severity and death in viral respiratory infections, suggest that obesity may increase the risk of another viral respiratory disease, COVID-19. Studies show that individuals with obesity suffer from COVID-19 disease more severely than individuals with normal body weight, and their intensive care unit needs are higher. Obesity is a risk factor for more severe COVID-19 disease due to a low-grade inflammatory condition and weakened immunity. There are studies in the literature showing that obesity as well as low body weight negatively affect the outcomes of COVID-19 disease. These studies revealed that COVID-19 patients with low body weight are at greater risk of mechanical ventilation and death. It has been observed that low body mass index and low body weight especially in infected elderly individuals increase the severity of COVID-19. Therefore, individuals having ideal body weight can prevent the negative consequences of COVID-19 disease. In addition, healthy nutrition plays an important role in the optimal functioning of the immune system and weight control. Keywords: COVID-19, obesity, underweight, immunity, nutrition

Cartilage explant model reflects resolvin D1 increase during recovery from LPS stimulation

Purpose: Osteoarthritis (OA) is a low-grade chronic inflammatory condition wherein the homeostatic balance of catabolic and anabolic processes favour the former, leading to a net decline in structural integrity of cartilage. The dissimilating pathways contributing to this decline have attracted much scientific scrutiny, with a host of pro-inflammatory cytokines and catabolic enzymes now known to orchestrate the protracted but eventual loss in joint function. Yet, amid the homeostatic badinage between repair and decline, there lies a wealth of reparative physiology which delays the tissue failure which characterizes clinical OA. An improved understanding of the interplay between pro-inflammatory and pro-resolving mediators can inform better management of early-stage OA, which can thus prolong healthy tissue function. Resolvin D1 (RvD1) is a pro-resolving mediator, which has been found to be dysregulated in rheumatoid arthritis and assists with resolving acute inflammation. The role of RvD1 in cartilage recovery from pro-inflammatory stimulation with lipopolysaccharide (LPS) is not known. We hypothesized that after an acute bout of inflammation in the articulating joint, cartilage-derived RvD1 is increased during the recovery phase, and thus participates in initiating inflammation resolution. The aim of this pilot study was to quantify production of RvD1 by cartilage explants following in vitro exposure to LPS. Methods: A single front limb from seven market weight pigs were collected and aseptically dissected extracting 0.4mm articular cartilage explants from the intercarpal joint. Explants were cultured in media (DMEM, antibiotics, amino acids) and incubated at 37°C and 7%CO2 for 168h. Media was removed and refreshed every 24h, following the first 48h of acclimatization explants were stimulated with LPS (0 or 10μg/mL) for 48h (collection time: 0h-S, 24h-S, 48h-S), followed by 48h of recovery (72h-R, 96h-R) in which media was refreshed without LPS stimulation. Media samples from the final 96h (0h-S to 96h-R) were collected every 24h during media changes and analyzed for nitric oxide (NO) (Greiss Reaction) and RvD1 (ELISA). Data were analyzed using a PROC GLIMMIX model (SAS Studio) looking at time-treatment interactions and visualized with two scatter plot graphs. Data are shown as mean±SEM and significance was accepted at p<0.05. Results: LPS stimulated explants elicited an increase in NO compared to controls from 0h-S to 48h-S and continued to increase until 72h-R (p=0.0006), as shown in Figure 1. RvD1 did not elicit a significant response to LPS stimulation but when graphed over time (0h-S to 96h-R) as seen in Figure 2, did visually show a change in response to stimulation and in comparison to its unstimulated controls. RvD1 response in unstimulated explants was elevated at 24h-R, (2109.40±188.56pg/mL) before continuously decreasing until 96h-R (1514.63±203.50pg/mL). RvD1 release in LPS stimulated explants decreased from 0h-S to 48h-S (0h: 1790.83±188.56pg/mL;48h:1489.11±203.50pg/mL) then increased until 96h-R (72h: 1743.28±177.16pg/mL; 96h:1814.47±177,17pg/mL).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Tamarind Multifunctional Protein: Safety and Anti-Inflammatory Potential in Intestinal Mucosa and Adipose Tissue in a Preclinical Model of Diet-Induced Obesity

Introduction: Obesity has emerged as one of the main public health problems. This condition triggers a series of hormonal and metabolic changes related to a low-grade chronic inflammatory condition. The trypsin inhibitor purified from tamarind (TTIp) seeds is a promising anti-inflammatory molecule, but its safety needs to be evaluated. This study aimed to evaluate TTIp bioactive dose effects on organs involved in its metabolism (liver and pancreas) and affected tissues (small intestine and perirenal adipose tissue) in an obesity model. Methods: Three groups of adult male Wistar rats were used (n = 5). Two of these groups had diet-induced obesity, and a third group was eutrophic. TTIp was administered by gavage in one of the obese groups for 10 days, while the remaining groups received a vehicle. The chromatographic profile and the inhibition assay corroded the purification of the inhibitor. Physical and behavioral changes, liver enzymes, and stereological and histopathological analyses of tissues were evaluated. Results: TTIp did not cause visible signs of toxicity, nor caused changes in liver enzymes, the liver, and pancreatic tissues. TTIp did not cause changes in the intestinal mucosa, showing improvement in the villi’s histopathological characteristics compared to the group of animals with obesity without treatment with TTIp (p = 0.004). The analysis of perirenal adipose tissue showed that the average sectional area of animals with obesity that received TTIp did not differ from the control. There was a difference between the high glycemic load diet group and the group treated with the inhibitor (351.8 ± 55.5) (p = 0.016). In addition, the group that received TTIp had no inflammatory infiltrates. Conclusion: Based on histological and stereological analysis, the use of TTIp is potentially safe and anti-inflammatory in the evaluated obesity model and can be investigated as a possible adjuvant in obesity therapy.

The Association between Hepcidin and Iron Status in Children and Adolescents with Obesity.

Introduction Iron deficiency (ID) is the most common nutritional deficiency found in pediatric practice. A higher prevalence of ID may be found in children with obesity. Obesity is a chronic low-grade inflammatory condition. It is postulated that inflammation increases hepcidin, a regulator of iron homeostasis. The aim of this study was to investigate the associations between iron status, hepcidin, and BMI-standard deviation score (BMI-SDS) in children with and without obesity. Methods A cross-sectional study of Thai children with obesity (5 to 15 years old) versus age- and sex-matched, nonobese controls was conducted. A total of 63 children with obesity and 27 controls were enrolled. Complete blood count, serum iron, ferritin, transferrin saturation, and total iron binding capacity were analyzed. Serum hepcidin-25 was assayed using a hepcidin ELISA Kit (Human Hepc25). Results There were 63 children with obesity, the median age (IQR) being 10 (9–13) years, and 27 controls. The median (IQR) BMI-SDS of the obese group was 2.3 (2.0–2.6) vs. −0.5 ((−1.3)−0.4) of the control group. ID was diagnosed in 27 children in the obese group (42.9%); 4 of the children with obesity and ID had anemia. Serum hepcidin-25 levels of the children with ID vs. without ID in the obese group were not significantly different (median (IQR) 25 (12.9–49.2) and 26.4 (12.6–43.6), respectively) but both of them were significantly higher than controls (19.7 (8.3–25.5) ng/ml, p = 0.04). BMI-SDS was positively correlated with hepcidin-25 (r = 0.28, p = 0.001). Conclusion Prevalence of iron deficiency in Thai children with obesity and serum hepcidin-25 was higher than controls. Further study in a larger population, preferably with interventions such as weight loss program, is warranted to clarify this association.

Weight and Body Mass Index Change After Switching to Integrase Inhibitors or Tenofovir Alafenamide Among Women Living with HIV.

Weight and body mass index (BMI) change was assessed among women after switch to integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF). From 2006 to 2019, 1,458 women living with HIV enrolled in the Women's Interagency HIV Study and on antiretroviral therapy (ART) with ≥1 study visit before and after switching to INSTIs and/or TAF were included. Weight and BMI were compared pre- and postswitch to INSTI (by class and type) and/or TAF using multivariable linear mixed effects models; all models were also stratified by preswitch presence or absence of obesity (BMI ≥30 vs. <30 kg/m2). Mean age preswitch was 47 ± 6 years, 64% were black, mean CD4 = 475 ± 201 cells/mm3, 56% had HIV RNA <200 copies/mL, 36% switched to TAF but not INSTI, 60% to INSTI but not TAF, and 3.5% to TAF+INSTI. Time from pre- to postswitch was 12.8 ± 11.8 months. The INSTI-only group but not TAF groups had small but significant increases in weight and BMI: mean 79.2-80.6 kg and 30.2-30.7 kg/m2, p's < .001, respectively, with congruent findings by INSTI type (p's ≤ .01). In stratified (preswitch BMI) analyses, only nonobese subgroups experienced increases in weight and BMI across all ART treatment groups (p's < .05). Significant, although small-to-medium, increases in weight and BMI occurred among nonobese women who switched to INSTIs and/or TAF over short follow-up. Given long-term health consequences of obesity particularly as a low-grade inflammatory condition, identifying women at highest risk of ART-associated weight gain is imperative.

COMPARISON BY SERUM HUMANIN BETWEEN WOMEN WITH PREECLAMPSIA AND WOMEN WITH UNCOMPLICATED PREGNANCIES

Background: Preeclampsia is thought to be a low-grade inflammatory condition with oxidative stress and endothelial dysfunction. Humanin is suggested to give protection against the development of endothelial dysfunction and atherosclerosis through the inhibition of apoptosis and oxidative stress. Objective: To evaluate the role of serum Humanin in the diagnosis and prediction of severity of preeclampsia. Methods: A case-control study conducted in the Department of Obstetrics and Gynecology at AL-Yarmouk Teaching Hospital / Baghdad, Iraq during a period from the 1st of July 2017 till the 1st of July 2018. It included 45 pregnant women diagnosed as preeclamptic (case group) and 45 women with uncomplicated pregnancy who were selected after matching for age and gestational age of another one in the case group (Control group).All the participants were submitted to blood sampling for biochemical/hormonal assays {urea, creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminse (SGPT), uric acid, platelets, urinary protein, Humanin). Results: There was no significant difference (P value ≥ 0.05) between women with preeclampsia and control regarding their age, body mass index, and gestational age. 57.8% of case group diagnosed as severe preeclampsia. The mean of serum Humanin concentration was significantly higher among women with preeclampsia than that in control group (473.1 versus 298.6 pg/ml P value 0.001); also it was significantly higher among women with severe preeclampsia than that in women with mild to moderate preeclampsia (491.6 versus 454.6 pg/ml, P value 0.001). Conclusion:Maternal serum Humanin was significantly higher in preeclamptic pregnant women than women with uncomplicated pregnancy. Maternal serum Humanin was significantly higher in pregnant women with sever preeclampsia than those with mild to moderate preeclampsia.

Influence of Obesity and Exercise on β2-Adrenergic-Mediated Anti-Inflammatory Effects in Peritoneal Murine Macrophages

Obesity is a chronic low-grade inflammatory condition, and β2-adrenergic agonists as well as exercise have been proposed as anti-inflammatory strategies in obesity, so it is critical to accurately determine the effects of β2-adrenergic stimulation, especially when combined with other non-pharmacological therapies. The aim of this investigation was to determine the effect of β2-adrenergic activation on the inflammatory profile and phenotype of macrophages, and whether these effects could be affected by obesity and exercise in this condition. High-fat diet-induced obese and lean C57BL/6J mice were allocated to sedentary or exercised groups. The inflammatory profiles and phenotypes of their peritoneal macrophages were assessed by flow cytometry in the presence or absence of the selective β2-adrenergic receptor agonist terbutaline. β2-adrenergic activation caused global phenotypic anti-inflammatory effects in lean and obese sedentary mice, which were more drastic (also including anti-inflammatory effects on the cytokine profile) in obese animals. In exercised lean and obese animals, this anti-inflammatory effect is weaker and only evident by decreased iNOS and IL-8 expression, without changes in the anti-inflammatory markers. Therefore, β2-adrenergic activation leads to anti-inflammatory effects, but these effects are modulated by obesity in sedentary conditions, as well as by regular exercise; but not by obesity in trained conditions.

Obese adipose tissue extracellular vesicles raise breast cancer cell malignancy.

Obesity is a chronic low-grade inflammatory condition that strongly impacts breast cancer. Aside from inflammatory mediators, obese adipose tissue (AT) secretes high amounts of extracellular vesicles (EVs), which are capable of transferring molecules to target cells and promoting cell-to-cell communication. Here, we investigated how soluble mediators and EVs secreted by human obese AT influence MCF-7 and MDA-MB-231 mammary adenocarcinoma cell lines by modulating cell proliferation, migration, invasion, and signaling pathways. Both cell lineages were stimulated with conditioned media (CM) or EVs obtained from cultures of AT explants collected from lean or obese individuals who underwent plastic or bariatric surgeries, respectively. EVs derived from obese AT increased the proliferative potential of both cell lines and further potentiated the migratory and invasive properties of MDA-MB-231 cells. The proliferative effects of CM and EVs on MCF-7 cells were dependent on ERK/MAPK pathway activation, while the migration and invasiveness of MDA-MB-231 cells were dependent on PI3K/AKT pathway activation. Furthermore, CM derived from obese AT potentiated the pro-angiogenic effect of MDA-MB-231 on endothelial cells. We also detected that EVs derived from obese AT were enriched in leptin and bioactive matrix metallopeptidase 9 (MMP9), and stimulation of MDA-MD-231 cells with those EVs or CM derived from obese AT potentiated the release of MMP9 by those cells. Our data indicate that obese AT secretes molecules and EVs with pro-tumoral activities capable of increasing breast cancer cell malignancy and provide strong evidence of the key role of AT-derived EV signaling in the tumor microenvironment.

Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin.

Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.

Linking mechanisms of periodontitis to Alzheimer's disease.

The review article discusses the association between periodontal disease and the development of dementia. In the last decade, increasing evidence has pointed to a microbial and inflammatory origin for Alzheimer's disease with the discovery of oral and airway bacteria, viruses, and fungal species in the brain of patients with Alzheimer's disease. Furthermore, recognized as the culprit of neural network dysfunction, β-amyloid oligomeric species have antimicrobial properties reinforcing the idea that dysbiosis in the host-microbiota interaction can be at the origin of dementia. Periodontitis (gum disease), a persistent low-grade inflammatory condition, caused by pathogenic microorganisms, has been linked to an increased β-amyloid burden and cognitive disabilities later in life. The pathogens of periodontal disease and the subsequent chronic inflammatory responses have significant implications on the development of Alzheimer's disease. The exact molecular mechanism by which Porphyromonas gingivalis and periodontal disease are involved in the pathogenicity of Alzheimer's disease is not currently evident. Understanding this causality can be instrumental in the development of treatments for this yet uncurable disease.