State Of Chronic Low-grade Inflammation Research Articles

Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model.

Inflammaging, a state of chronic low-grade inflammation associated with aging, has been linked to the development and progression of various disorders. Cellular senescence, a state of irreversible growth arrest, is another characteristic of aging that contributes to the pathogenesis of cardiovascular pathology. Senescent cells accumulate in tissues over time and secrete many inflammatory mediators, further exacerbating the inflammatory environment. This senescence-associated secretory phenotype can promote tissue dysfunction and remodeling, ultimately leading to the development of age-related cardiovascular pathologies, such as mitral valve myxomatous degeneration. The species-specific form of canine myxomatous mitral valve disease (MMVD) provides a unique opportunity to investigate the early causes of induction of ECM remodeling in mitral valve leaflets in the human form of MMVD. Studies have shown that in both humans and dogs, the microenvironment of the altered leaflets is inflammatory. More recently, the focus has been on the mechanisms leading to the transformation of resting VICs (qVICs) to myofibroblast-like VICs (aVICs). Cells affected by stress fall into a state of cell cycle arrest and become senescent cells. aVICs, under the influence of TGF-β signaling pathways and the mTOR complex, enhance ECM alteration and accumulation of systemic inflammation. This review aims to create a fresh new view of the complex interaction between aging, inflammation, immunosenescence, and MMVD in a canine model, as the domestic dog is a promising model of human aging and age-related diseases.

Poor muscle quality: A hidden and detrimental health condition in obesity.

Poor muscle quality (MQ) is a hidden health condition in obesity, commonly disregarded and underdiagnosed, associated with poor health-related outcomes. This narrative review provides an in-depth exploration of MQ in obesity, including definitions, available assessment methods and challenges, pathophysiology, association with health outcomes, and potential interventions. MQ is a broad term that can include imaging, histological, functional, or metabolic assessments, evaluating beyond muscle quantity. MQ assessment is highly heterogeneous and requires further standardization. Common definitions of MQ include 1) muscle-specific strength (or functional MQ), the ratio between muscle strength and muscle quantity, and 2) muscle composition (or morphological MQ), mainly evaluating muscle fat infiltration. An individual with obesity might still have normal or higher muscle quantity despite having poor MQ, and techniques for direct measurements are needed. However, the use of body composition and physical function assessments is still limited in clinical practice. Thus, more accessible techniques for assessing strength, muscle mass, and composition should be further explored. Obesity leads to adipocyte dysfunction, generating a low-grade chronic inflammatory state, which leads to mitochondrial dysfunction. Adipocyte and mitochondrial dysfunction result in metabolic dysfunction manifesting clinically as insulin resistance, dyslipidemia, and fat infiltration into organs such as muscle, which in excess is termed myosteatosis. Myosteatosis decreases muscle cell function and insulin sensitivity, creating a vicious cycle of inflammation and metabolic derangements. Myosteatosis increases the risk of poor muscle function, systemic metabolic complications, and mortality, presenting prognostic potential. Interventions shown to improve MQ include nutrition, physical activity/exercise, pharmacology, and metabolic and bariatric surgery.

Pathophysiological Role of Neutrophil Extracellular Traps in Diet-Induced Obesity and Metabolic Syndrome in Animal Models.

The global pandemic of obesity poses a serious health, social, and economic burden. Patients living with obesity are at an increased risk of developing noncommunicable diseases or to die prematurely. Obesity is a state of chronic low-grade inflammation. Neutrophils are first to be recruited to sites of inflammation, where they contribute to host defense via phagocytosis, degranulation, and extrusion of neutrophil extracellular traps (NETs). NETs are web-like DNA structures of nuclear or mitochondrial DNA associated with cytosolic antimicrobial proteins. The primary function of NETosis is preventing the dissemination of pathogens. However, neutrophils may occasionally misidentify host molecules as danger-associated molecular patterns, triggering NET formation. This can lead to further recruitment of neutrophils, resulting in propagation and a vicious cycle of persistent systemic inflammation. This scenario may occur when neutrophils infiltrate expanded obese adipose tissue. Thus, NETosis is implicated in the pathophysiology of autoimmune and metabolic disorders, including obesity. This review explores the role of NETosis in obesity and two obesity-associated conditions-hypertension and liver steatosis. With the rising prevalence of obesity driving research into its pathophysiology, particularly through diet-induced obesity models in rodents, we discuss insights gained from both human and animal studies. Additionally, we highlight the potential offered by rodent models and the opportunities presented by genetically modified mouse strains for advancing our understanding of obesity-related inflammation.

Unraveling the ROS-Inflammation-Immune Balance: A New Perspective on Aging and Disease.

Increased entropy is a common cause of disease and aging. Lifespan entropy is the overall increase in disorder caused by a person over their lifetime. Aging leads to the excessive production of reactive oxygen species (ROS), which damage the antioxidant system and disrupt redox balance. Organ aging causes chronic inflammation, disrupting the balance of proinflammatory and anti-inflammatory factors. Inflammaging, which is a chronic low-grade inflammatory state, is activated by oxidative stress and can lead to immune system senescence. During this process, entropy increases significantly as the body transitions from a state of low order to high disorder. However, the connection among inflammation, aging, and immune system activity is still not fully understood. This review introduces the idea of the ROS-inflammation-immune balance for the first time and suggests that this balance may be connected to aging and the development of age-related diseases. We also explored how the balance of these three factors controls and affects age-related diseases. Moreover, imbalance in the relationship described above disrupts the regular structures of cells and alters their functions, leading to cellular damage and the emergence of a disorganized state marked by increased entropy. Maintaining a low entropy state is crucial for preventing and reversing aging processes. Consequently, we examined the current preclinical evidence for antiaging medications that target this balance. Ultimately, comprehending the intricate relationships between these three factors and the risk of age-related diseases in organisms will aid in the development of clinical interventions that promote long-term health.

Effect of Diet on HDL in Obesity.

Alterations of plasma lipoprotein levels and oxidative stress are frequently observed in obese patients, including low high-density lipoprotein (HDL) cholesterol (HDL-C) levels and alterations of HDL composition. Dysfunctional HDL with lower antioxidant and anti-inflammatory properties have also been demonstrated in obesity. There is increasing evidence that white adipose tissue (WAT) participates in several metabolic activities and modulates HDL-C levels and function. In obese subjects, the changes in morphology and function of adipose tissue lead to impaired regulatory function and are associated with a state of low-grade chronic inflammation, with increased release of pro-inflammatory adipokines and cytokines. These alterations may affect HDL metabolism and functions; thus, adipose tissue is considered a potential target for the prevention and treatment of obesity. A cornerstone of obesity prevention and therapy is lifestyle modification through dietary changes, which is reflected in the modulation of plasma lipoprotein metabolism. Some dietary components and metabolites directly affect the composition and structure of HDL and modulate its anti-inflammatory and vasoprotective properties. The aims of the review are to summarize the crosstalk between adipocytes and HDL dysfunction in human obesity and to highlight recent discoveries on beneficial dietary patterns as well as nutritional components on inflammation and HDL function in human obesity.

The Impact of Exercise and Protein Intake on Inflammaging: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

Sarcopenia and cachexia lead to muscle wasting and increased health risks in older adults. Both sarcopenia and cachexia are associated with inflammaging, a chronic low-grade inflammatory state linked to aging. Strategies to preserve muscle mass and function are crucial for maintaining independence and quality of life among the elderly. This meta-analysis and systematic review was conducted to comprehensively assess the individual and combined effects of exercise training and protein supplementation on circulatory markers of inflammation in older adults. A systematic search of the PubMed, Scopus, Cochrane CENTRAL, and SPORTDiscus databases was conducted to identify relevant studies published until January 2024. The search focused on randomized controlled trials examining the impact of exercise training (Ex), protein consumption (Pro), or their combination (Ex-Pro) on inflammatory factors, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) compared with a control (Con). The meta-analysis revealed a significant decrease in CRP levels in the Ex vs Pro (P = .0003) and the Ex-Pro (P < .00001) group compared with the Ex group and in overall experimental (EXPL) subgroups (P = .0002) compared with the Con group. A similar reduction was found in IL-6 in the Ex group (P = .001), Ex-Pro group (P = .05), and EXPL (P = .0002) subgroup compared with the Pro group. However, for TNF-α levels, a significant reduction was noted only in the Ex-Pro group compared with the Ex group (P < .00001). Exercise training and protein supplementation, particularly when combined, show greater benefits in mitigating inflammaging. These findings highlight the importance of combined interventions against muscle wasting. Future studies and meta-analyses should further address the effects of Ex and Pro and Ex-Pro on inflammatory markers of older adults, considering specific conditions and larger sample sizes to identify optimal strategies for the aging population.

Lingguizhugan decoction alleviates obesity in rats on a high-fat diet through the regulation of lipid metabolism and intestinal microbiota.

Individuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment. Fifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) to assess gut microbiota and SCFA levels. LGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL. LGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation.

Malnutrition in patients with obesity: An overview perspective.

Malnutrition in patients with obesity presents a complex and often overlooked clinical challenge. Although obesity is traditionally associated with overnutrition and excessive caloric intake, it can also coincide with varying degrees of malnutrition. The etiopathogenesis of obesity is multifaceted and may arise from several factors such as poor diet quality, nutrient deficiencies despite excess calorie consumption, genetics, and metabolic abnormalities affecting nutrient absorption and utilization. Moreover, a chronic low-grade inflammatory state resulting from excess adipose tissue, commonly observed in obesity, can further exacerbate malnutrition by altering nutrient metabolism and increasing metabolic demands. The dual burden of obesity and malnutrition poses significant risks, including immune dysfunction, delayed wound healing, anemia, metabolic disturbances, and deficiencies in micronutrients such as vitamin D, iron, magnesium, and zinc, among others. Malnutrition is often neglected or not given enough attention in individuals with obesity undergoing rapid weight loss through aggressive caloric restriction, pharmacological therapies, and/or surgical interventions. These factors often exacerbate vulnerability to nutrition deficiencies. We advocate for healthcare practitioners to prioritize nutrition assessment and initiate medical intervention strategies tailored to address both excessive caloric intake and insufficient consumption of essential nutrients. Raising awareness among healthcare professionals and the general population about the critical role of adequate nutrition in caring for patients with obesity is vital for mitigating the adverse health effects associated with malnutrition in this population.

10-Gingerol Increases Antioxidant Enzymes and Attenuates Lipopolysaccharide-Induced Inflammation by Modulating Adipokines in 3T3-L1 Adipocytes.

Obesity increases reactive oxygen species production and alters adipokines levels, resulting in a low-grade chronic inflammation state, which contributes to tissue metabolic dysfunction. 10-gingerol, a phenol present in ginger, has shown potential anti-obesogenic effects in vitro. However, the antioxidant and anti-inflammatory properties of 10-gingerol have not been approached. The aim of this study was to investigate the effects of 10-gingerol on antioxidant enzymes' expression and adipokine production in 3T3-L1 adipocytes in response to lipopolysaccharide (LPS)-induced inflammation. 10-gingerol antioxidant capacity was assessed through Oxygen Radical Absorbance Capacity (ORAC) , Ferric Reducing Antioxidant Power (FRAP), and radical scavenging activity of 2,2-diphenyl-2-picrylhydrazyl (DPPH) assays. 3T3-L1 cells were differentiated and stimulated with 100 ng/mL LPSs. Then, 15 µg/mL 10-gingerol was added for 48 h. The mRNA expression and protein abundance of antioxidant enzymes were evaluated by qPCR and Western blot, respectively. Adipokine levels were determined by ELISA. 10-gingerol showed low FRAP and DPPH values but a moderate ORAC value. Moreover, 10-gingerol increased Gpx1 and Sod1 but downregulated Cat expression. Additionally, 10-gingerol significantly increased CAT and GPx1 levels but not SOD-1. Finally, adiponectin and leptin concentrations were increased while resistin and tumor necrosis factor alpha (TNFα) were decreased by 10-gingerol. 10-gingerol presented antioxidant potential by increasing antioxidant enzymes and attenuated LPS-induced inflammation by modulating adipokines in 3T3-L1 adipocytes.

Impaired glycemic control as a risk factor for reduced lung function in the Indian diabetic population

Diabetes mellitus (DM) is a metabolic syndrome associated with chronic hyperglycemia, which results in various acute and chronic complications. DM leads to a state of chronic low-grade inflammation, which can have adverse effects on pulmonary functions. There have been contradictory studies related to the relationship between defects in lung functions in diabetic individuals and their correlation with glycemic control and systemic inflammatory markers. The present study aims to compare pulmonary function in controlled and uncontrolled diabetes in the Indian population while exploring the link between inflammatory markers and lung functions in diabetic patients. This observational, case-control study was conducted in the Department of Biochemistry at Sri Guru Ram Das Institute of Medical Sciences and Research in Amritsar, Punjab, on 116 subjects suffering from DM in the age group of 30-65 years. 58 diabetic patients with poor glycemic control [glycated hemoglobin (HbA1c)&gt;7%] and 58 diabetic patients with good glycemic control served as controls (HbA1c≤7%). The duration of the study was two years. Blood samples of each patient were investigated for glycemic control, high-sensitivity C-reactive protein (hsCRP), and serum fibrinogen. Spirometry as a pulmonary function test was undertaken for all participants. The statistical analysis of good and poor glycemic control diabetics showed that the average duration of disease (in years) was 8±5 and 10.2±5.4, respectively. A significant positive correlation was found between inflammatory markers (hsCRP and fibrinogen) and HbA1c and fasting blood glucose. A substantial decline in forced vital capacity and normal values of forced expiratory volume in the first second was observed in poor glycemic control diabetics, depicting a restrictive pattern of lung disease. Lung damage is seen to be more prevalent in patients with a longer duration of disease and increased levels of inflammatory markers. Chronic inflammation due to DM can lead to fibrosis and destruction of lung tissue, resulting in the development of diabetic lung disease, which includes a decline in lung function, an increased risk of infection, and an increased risk of respiratory failure. Therefore, it is essential for individuals with DM to have regular pulmonary function tests and to manage their diabetes to minimize the impact on their lung health.

Role of Follistatin-Like 1 in Development of Insulin Resistance in Overweight and Obese Children

Abstract The increasing prevalence of childhood obesity is considered a public health issue in both developed and developing countries. The state of chronic low-grade inflammation associated with obesity contributes to the development of insulin resistance. However, the molecular mechanisms that link obesity to inflammation are not fully understood. Follistatin-like 1 (FSTL1) is a proinflammatory cytokine that is expressed in adipose tissue and secreted by preadipocytes/adipocytes. The aim of this study is to evaluate serum level of FSTL1 in overweight/obese children as compared to normal healthy subjects, and correlate serum FSTL1 level with inflammation and insulin resistance. Our work showed that overweight and obese children had significantly higher levels of serum FSTL1, high sensitivity C-reactive protein (hs-CRP) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). In conclusion, serum FSTL1 can be a useful biomarker for obesity in children. Moreover, FSTL1, being a pro inflammatory cytokine, may provide a possible link between obesity, inflammation, and the development of insulin resistance in the overweight/obese children.

Leuko-glycemic index as a marker of inflammation and endothelial dysfunction in overweight and obesity

Overweight (OW) and obesity (OB) are major health problems both in Mexico and the world. Because of the chronic low-grade inflammatory state that characterizes OW and OB, they are considered as cardiovascular risk factors. The leuko-glycemic index (LGI) is a ratio used as a prognostic factor to predict complications in patients with vascular diseases. To assess the utility of LGI index as an inflammatory and endothelial dysfunction marker in patients with OW and OB. Comparative cross-sectional study in 124 patients of Family Medicine Unit 80 of Mexican Social Security Institute. Young adults aged between 18 - 50 years old, and BMI between 18.5 and 40 kg/m2, without diagnosis of chronic diseases, auto immunities or immunodeficiencies were included. Bioelectrical impedance (weight, height, BMI, % body fat, lean mass) and blood sample (blood count, glucose, lipid profile, inflammatory, endothelial dysfunction markers) were assessed. Patients were grouped according to their BMI: OB, OW and normal weight (NW). LGI was found to be significantly elevated in OB and OW patients vs. NW. LGI correlated positively with inflammation and DE markers: IL-6, TNF-α, vWF. A value ≥ 405 was estimated with ROC curves as cut-off point for LGI to predict the likelihood of inflammation and ED in OW and OB patients. ILG is relevant as a predictive marker of cardiovascular disease by reflecting inflammation and endothelial dysfunction in patients with OW and OB.

Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications.

Aging leads to physiological changes, including inflammaging-a chronic low-grade inflammatory state with significant implications for various physiological systems, particularly for cardiovascular health. Concurrently, immunosenescence-the age-related decline in immune function, exacerbates vulnerabilities to cardiovascular pathologies in older individuals. Examining the dynamic connections between immunosenescence, inflammation, and cardiovascular aging, this mini-review aims to disentangle some of these interactions for a better understanding of their complex interplay. In the context of cardiovascular aging, the chronic inflammatory state associated with inflammaging compromises vascular integrity and function, contributing to atherosclerosis, endothelial dysfunction, arterial stiffening, and hypertension. The aging immune system's decline amplifies oxidative stress, fostering an environment conducive to atherosclerotic plaque formation. Noteworthy inflammatory markers, such as the high-sensitivity C-reactive protein, interleukin-6, interleukin-1β, interleukin-18, and tumor necrosis factor-alpha emerge as key players in cardiovascular aging, triggering inflammatory signaling pathways and intensifying inflammaging and immunosenescence. In this review we aim to explore the molecular and cellular mechanisms underlying inflammaging and immunosenescence, shedding light on their nuanced contributions to cardiovascular diseases. Furthermore, we explore the reciprocal relationship between immunosenescence and inflammaging, revealing a self-reinforcing cycle that intensifies cardiovascular risks. This understanding opens avenues for potential therapeutic targets to break this cycle and mitigate cardiovascular dysfunction in aging individuals. Furthermore, we address the implications of Long COVID, introducing an additional layer of complexity to the relationship between aging, immunosenescence, inflammaging, and cardiovascular health. Our review aims to stimulate continued exploration and advance our understanding within the realm of aging and cardiovascular health.

Local Application of Tanshinone IIA protects mesenchymal stem cells from apoptosis and promotes fracture healing in ovariectomized mice

BackgroundElderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing.MethodsMSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel.ResultsTanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation.ConclusionsTaken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.

Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents.

Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

Equisetum arvense standardized dried extract hinders age-related osteosarcopenia

Age-associated osteosarcopenia is an unresolved syndrome characterized by the concomitant loss of bone (osteopenia) and skeletal muscle (sarcopenia) tissues increasing falls, immobility, morbidity, and mortality. Unbalanced resorption of bone in the remodeling process and excessive protein breakdown, especially fast type II myosin heavy chain (MyHC-II) isoform and myofiber metabolic shift, are the leading causes of bone and muscle deterioration in the elderly, respectively. Equisetum arvense (EQ) is a plant traditionally recommended for many pathological conditions due to its anti-inflammatory properties. Thus, considering that a chronic low-grade inflammatory state predisposes to both osteoporosis and sarcopenia, we tested a standardized hydroalcoholic extract of EQ in in vitro models of muscle atrophy [C2C12 myotubes treated with proinflammatory cytokines (TNFα/IFNγ), excess glucocorticoids (dexamethasone), or the osteokine, receptor activator of nuclear factor kappa-B ligand (RANKL)] and osteoclastogenesis (RAW 264.7 cells treated with RANKL). We found that EQ counteracted myotube atrophy, blunting the activity of several pathways depending on the applied stimulus, and reduced osteoclast formation and activity. By in silico target fishing, IKKB-dependent nuclear factor kappa-B (NF-κB) inhibition emerges as a potential common mechanism underlying EQ′s anti-atrophic effects. Consumption of EQ (500 mg/kg/day) by pre-geriatric C57BL/6 mice for 3 months translated into: i) maintenance of muscle mass and performance; ii) restrained myofiber oxidative shift; iii) slowed down age-related modifications in osteoporotic bone, significantly preserving trabecular connectivity density; iv) reduced muscle- and spleen-related inflammation. EQ can preserve muscle functionality and bone remodeling during aging, potentially valuable as a natural treatment for osteosarcopenia.

Intereleukine-6 and Interleukine-1β levels in post-traumatic stress disorder, depression and healthy controls: a preliminary report

IntroductionPatients with Post-traumatic stress disorder (PTSD) or mood disorders, as depression, often showed dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, resulting in increased levels of pro-inflammatory cytokines and heightened activity of the immune system that may cause alterations in the structure and function of brain regions through direct neurotoxic effects, oxidative stress, changes in levels of neurotransmitters and decreasing some neurotrophins. Among the most studied pro-inflammatory cytokines in this field there are Intereleukine-6 (IL-6) and Interleukine-1β (IL-1β); however, scant and conflicting data are currently available in the literature about their use as potential biomarkers, and even less on possible comparisons in PTSD and depression.Objectives The aim of the present study was to evaluate circulating levels of IL-6 and IL-1β in patients with PTSD and to compare them with those of subjects with depression and healthy controls.MethodsA sample of 45 subjects, including 15 subjects diagnosed with PTSD (PTSD group), 15 with depression (DEP group), and 15 healthy controls (HC group) were recruited at the Psychiatric Clinic of the Department of Clinical and Experimental Medicine, University of Pisa. HC group included subjects recruited on a voluntary basis. The psychiatric diagnosis was assessed by the Structured Clinical Interview for DSM-5-Clinician Version (SCID-5-CV), the Impact of Event Scale-Revised (IES-R) and the Trauma and Loss Spectrum-Self Report lifetime version (TALS-SR). A peripheral venous blood sample was collected to perform the biochemical assays. The analyses of IL-6 and IL-1β were performed with a dedicated enzyme-linked immunosorbent assay (ELISAs) achieved at the Laboratory of Biochemistry of the Department of Pharmacy, University of Pisa.ResultsNo statistically significant gender or age differences emerged in the three groups. There were no statistically significant differences in IL-1β levels among the three groups. Conversely, the PTSD group showed higher levels of IL-6 compared to the DEP and to the HC ones, with a statistically significant difference in the post-hoc analysis among the PTSD and DEP groups with respect to the HC one (p&lt;0.05).ConclusionsOur results suggest the key role of a chronic low-grade inflammatory state in PTSD and in depression, probably related to a dysregulation in HPA axis and cortisol release, with an increase in proinflammatory cytokines including IL-6 that seemed to be more pronounced in PTSD.Disclosure of InterestNone Declared

Beyond blood sugar: exploring the anti-inflammatory frontier of antidiabetic medications to alleviate diabetic complications

Background and objective. Inflammation is closely correlated with diabetes and diabetic complications. Research has shown that individuals with diabetes exhibit an upregulation of circulatory proinflammatory cytokines, resulting in a chronic state of low-grade inflammation. The participation of inflammation in the pathogenesis of diabetic complications, particularly cardiovascular and renal complications, is well-established. Targeting inflammation may produce prominent effects in improving the clinical condition of diabetic patients, reducing the progression of complications, and promoting glucose uptake by insulin-sensitive tissues. This review article aimed to explore the anti-inflammatory effect of antidiabetics beyond their hypoglycemic action and the potential effects of such antidiabetics in reducing diabetic complications. Materials and methods. Based on relevant online publications using the terms anti-diabetics, anti-inflammatory, diabetic complications, and inflammatory mediators up to February 2024 on PubMed and Google Scholar were utilized to construct this review. Results. The majority of antidiabetic drugs pose an indirect effect on inflammation through the hypogly­cemic effect. However, many antidiabetics have an additional anti-inflammatory mechanism independently of their hypoglycemic effects, which augments their anti-inflammatory effects. Conclusion. Suppression of the inflammatory response by anti-diabetics and achieving homeostatic control is an effective approach for preventing diabetic complications.

Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice.

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation, known as meta-inflammation. This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease. Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways. However, its role and molecular mechanism in obesity and associated complications are obscure. In this study, we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain, white adipose tissue inflammation, and metabolic dysregulation. To identify the target proteins of pyruvate, drug affinity responsive target stability was employed with proteomics, cellular thermal shift assay, and isothermal drug response to detect the interactions between pyruvate and its molecular targets. Consequently, we identified cytosolic phospholipase A2 (cPLA2) as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity, white adipose tissue inflammation, and hepatic steatosis in a cPLA2-dependent manner. Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated, confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity. Overall, our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action. Pyruvate's prior clinical use indicates that it can be considered a safe and viable alternative for obesity, whether consumed as a dietary supplement or as part of a regular diet.

Association Between Pro-inflammatory Cytokine Levels (IL-1β, IL-6, and TNF-α) in Human Colostrum and Maternal Body Composition Components.

Background: Obesity is characterized as a low-grade chronic inflammatory state, marked by elevated inflammatory biomarkers. Breast milk (BM) is rich in nutritional elements, vitamins, minerals, immunological factors, and bioactive components. These bioactive components, capable of influencing biological processes, may vary in concentration based on maternal body composition. Research Aim/Question(s): This study aimed to explore the association between pro-inflammatory cytokine levels (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) in human colostrum and maternal body composition, as analyzed through bioelectrical impedance vector analysis (BIVA). Method: In this cross-sectional study, 117 healthy postpartum participants were included, with each group (normal weight, overweight, and obese) comprising 39 individuals, as classified by BIVA. Colostrum samples were collected within the first 24 hours postpartum. Results: IL-1β levels did not significantly differ across the groups, with concentrations of 69.5 ± 103 pg/mL in normal-weight, 79.7 ± 97.9 pg/mL in overweight, and 68.7 ± 108 pg/mL in obese women. IL-6 levels were significantly higher in the overweight group (55 ± 72.4 pg/mL) than in the normal-weight (48.1 ± 74.1 pg/mL) and obese groups (28.9 ± 36.2 pg/mL) (p = 0.02). Similarly, TNF-α levels were higher in the overweight group, with concentrations of 58.7 ± 74.9 pg/mL, than in the normal-weight group, with concentrations of 38.6 ± 95.4 pg/mL, and 52.6 ± 115 pg/mL in obese women (p = 0.02). Conclusion: This study shows that IL-6 and TNF-α concentrations were statistically higher in the colostrum of overweight women, suggesting that maternal body composition may influence the inflammatory profile of BM.