Low-grade Inflammatory State Research Articles

Therapeutic Potential of Citrus Flavonoids in Metabolic Inflammation and Insulin Resistance

Metabolic inflammation, or meta-inflammation, is a low-grade chronic inflammatory state associated with metabolic disorders such as obesity, type 2 diabetes mellitus (T2DM), and insulin resistance (IR). Recent evidence highlights the role of bioactive compounds, particularly citrus flavonoids, in modulating metabolic pathways and inflammatory responses. Citrus flavonoids, such as hesperidin, naringenin, nobiletin, and tangeretin, exhibit diverse biological properties including antioxidant, anti-inflammatory, and insulin-sensitizing effects. This review consolidates current findings on the molecular mechanisms through which citrus flavonoids exert protective effects against metabolic inflammation and insulin resistance. These compounds target multiple signaling pathways including NF-κB, AMPK, PI3K/Akt, and PPARγ, thereby regulating cytokine expression, glucose uptake, lipid metabolism, and oxidative stress. Clinical and preclinical studies are also discussed, providing insight into the translational potential of citrus flavonoids as adjuncts in the management of metabolic diseases. Furthermore, challenges in bioavailability and future research directions aimed at enhancing the efficacy of these natural compounds are highlighted. Overall, citrus flavonoids represent a promising therapeutic avenue for alleviating metabolic inflammation and improving insulin sensitivity. Keywords: Citrus flavonoids, metabolic inflammation, insulin resistance, hesperidin, naringenin, NF-κB, AMPK, oxidative stress, type 2 diabetes mellitus

Pawsitive impact: How pet contact ameliorates adult inflammatory stress responses in individuals raised in an urban environment.

Pawsitive impact: How pet contact ameliorates adult inflammatory stress responses in individuals raised in an urban environment.

Identification of Immune Hub Genes in Obese Postmenopausal Women Using Microarray and Single-Cell RNA Seq Data

Background: Obesity is characterized by a chronic state of low-grade inflammation. Investigating immune-critical genes and their biological functions in the adipose tissue of postmenopausal obese women is crucial for elucidating the underlying mechanisms of immune dysregulation associated with obesity. Methods: In this study, microarray (GSE151839) and single-cell RNA-seq (GSE176171) datasets were obtained from the Gene Expression Omnibus (GEO). For microarray data analysis, weighted gene co-expression network analysis (WGCNA), protein–protein interaction network (PPI) analysis, and immune infiltration analysis (ssGSEA) were employed to identify obesity-related immune-critical genes. Subsequently, the candidate genes were validated using scRNA-seq data to explore their expression patterns at the single-cell level. Finally, the expression levels of these immune-critical genes were experimentally verified in adipose tissue from obese and control zebrafish models using RT-qPCR. Results: Analysis of microarray data through WGCNA, PPI and ssGSEA identified 16 obesity-related immune-critical genes, including IL7R, CD3E, CD2, CCR5, CD3D, MS4A1, TRAT1, SLAMF8, CCL3L1, SPP1, CCL5, IL2RG, CD3G, TLR8, ITK, and CCL3. Differential expression of SPP1, ITK and CCL5 was confirmed in scRNA-seq data, with ITK and CCL5 showing distinct expression patterns in natural killer (NK) cells. Furthermore, RT-qPCR analysis revealed upregulation of SPP1 and ITK in adipose tissue of obese zebrafish compared to lean controls. Conclusions: This study identifies SPP1, ITK and CCL5 as key immune hub genes in the adipose tissue of postmenopausal obese women, with NK cells playing a significant role in adipose tissue inflammation through the expression of these genes. These findings provide novel insights into potential therapeutic targets for the prevention and treatment of obesity in postmenopausal women.

1784-P: Anti-inflammatory Effects of Liraglutide in Obesity

Introduction and Objective: Obesity is not only a metabolic condition but also a state of chronic low-grade inflammation. While long-acting glucagon-like peptide-1 receptor agonists like liraglutide have demonstrated significant benefits in weight reduction, and glycemic control, their role in modulating inflammatory markers remains underexplored. This study aimed to evaluate the anti-inflammatory effects of a liraglutide in drug-naïve patients with obesity. Methods: In this prospective, single-center study, 23 adult patients with obesity underwent 3 mg liraglutide therapy for 12 weeks. Anthropometric measurements and blood samples were collected at baseline and post-treatment. Blood samples were analyzed for key inflammatory and metabolic markers, including resistin, adiponectin, cystatin C, PAI-1, leptin, ferritin, insulin, and a range of cytokines (IL-1A, IL-1B, IL-4, IL-6, IL-8, IL-10, TNFA, VEGF, MCP-1, and EGF). Statistical analyses, including paired t-tests and Wilcoxon signed-rank tests, were performed using IBM SPSS®. Results: Study participants lost > 5% of body weight. Liraglutide treatment significantly reduced pro-inflammatory markers such as IL-6 (p = 0.0342), PAI-1 (p = 0.003), resistin (p = 0.003), and leptin (p < 0.001), along with adiponectin (p = 0.047), cystatin C (p < 0.001), and EGF (p = 0.013). Interestingly, MCP-1 levels significantly increased (p = 0.012), suggesting a nuanced inflammatory response. Conclusion: Our study demonstrates that liraglutide exerts a significant anti-inflammatory effect in patients with obesity. The observed increase in MCP-1 may reflect a compensatory mechanism or a differential immune modulation that warrants further investigation. These findings suggest liraglutides’ dual role in addressing metabolic dysfunction and inflammation in obesity. Disclosure A.A. Alfadda: Consultant; Eli Lilly and Company. Other Relationship; Novo Nordisk. Consultant; Novo Nordisk. Research Support; Ministry of Education, Saudi Arabia, King Saud University, Saudi Arabia, King Abdulaziz City for Science and Technology, Saudi Arabia, Hevolution Foundation, Saudi Arabia, Dallah Hospital, Saudi Arabia. Other Relationship; Eli Lilly and Company, Novo Nordisk. N.A. Alfadda: None. K.A. Alfadda: None. H.S. Alrushud: None. M. Rafiullah: None. B. Alsuwayni: None. A.M. Alhossan: None. A. Masood: None. A. Fallata: None. T.P. George: None. S.S. Nawaz: None. Funding This research project was supported by the National Plan for Science, Technology, and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Saudi Arabia for Project No. 08-MED513-02 at Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Age-associated changes in the lymphoid tissues of Boa constrictor

Aging is a complex and multifaceted biological process that results in the gradual decline of physiological functions over time. It is associated with reduced performance across multiple systems, affecting metabolic, reproductive, musculoskeletal, and immune functions. While immune aging has been extensively studied in endothermic animals, and in particular mammals such as laboratory rodents, comparatively little is known about how aging manifests in ectothermic vertebrates like reptiles. This study explored the lymphoid tissue (spleen and thymus) of Boa constrictor, a boid snake indigenous to South and Central America and Mexico, but widely kept in captivity all over the world, for potential age-related changes. We observed a significant decrease in cellularity in the spleen, coupled with an increase in organ size correlated with age. In both spleen and thymus the connective tissue of capsule and trabeculae increased significantly with age, indicative of progressive fibrosis. In addition, several changes were observed with increasing frequency in older animals, epithelial hyperplasia in the thymic medulla as well stromal fibrosis and an increasing infiltration by so-called granular cells in both organs. Granular cells likely represent a leukocyte subtype; their presence indicates a progressive chronic low-grade inflammatory state in the lymphoid organs, a feature known as inflammaging in other animal classes. They may also play a role in the progressive fibrosis of the connective tissue. The results firstly describe morphological evidence of aging in B. constrictor and indicate similarities in the aging across animal classes.

An engineered adipose formulation decreases hepatic inflammation and fibrosis in a rodent model of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive stage metabolic dysfunction-associated steatohepatitis (MASH) represent a leading cause of liver-related morbidity and mortality in the U.S. and worldwide. Given the high prevalence and rapid growth of MASLD, the economic and health burden, and MASH-associated morbidity and mortality, there is an unmet medical need for therapies that can stop, slow, or reverse the progression of MASLD. Adipose tissue plays a key role in metabolic health and MASLD pathogenesis through its regulation of energy metabolism and endocrine function. Metabolic dysfunction is often associated with a chronic state of low-grade inflammation in the body including adipose tissue. In this study, we tested an engineered adipose formulation (AF) composed of a combination of culture-expanded adipose stromal vascular fraction (SVF) cells and adipose tissue particulates in the treatment of MASLD. Human, rat, and mouse AFs (hAF, rAF, and mAF) showed anti-inflammatory activity, which was mediated predominantly by soluble factors present in the adipose particulate. In vivo effects of AFs were evaluated in two rodent models of MASLD: i) obese Zucker rats fed a high-fat, high-cholesterol, and high-fructose diet that mainly manifest hepatic steatosis; and ii) liver-specific CGI-58 knockout mice (LivKO) on a Western diet that display MASH pathologies. Subcutaneous implantation of hAF and rAF in obese Zucker rats significantly reduced hepatic triglycerides. In LivKO mice, mAF reduced hepatic inflammation and fibrosis, though not steatosis, as evidenced by significant decreases in hepatic M1 macrophages and mRNAs for proinflammatory and fibrogenic genes. Immunogenicity testing demonstrated that allogeneic rAF did not induce an immune response, whereas, as anticipated, xenogeneic hAF in rats triggered anti-hAF antibody formation. Despite an immune response against xenogeneic hAF, treatment of rats with hAF ameliorated hepatic steatosis. AF has the potential to treat MASH. Future studies focused on the optimization of AF composition, optimal dose and treatment regimen are warranted.

Inflammation molecular network alterations in a depressive-like primate model.

Inflammation molecular network alterations in a depressive-like primate model.

Endotoxemia-induced inflammation in the absence of obesity decreases anxiety-like and impulsive behavior without affecting learning and memory

Obesity is associated with increased gut permeability, which contributes to a state of chronic low-grade inflammation. Obesity is also linked with altered neurocognitive functions, including impaired learning and memory. Whether these changes are secondary to neuroinflammation vs. other comorbidities associated with obesity is unknown. Here, we modeled the chronic low-grade inflammation that accompanies diet-induced obesity, but in the absence of obesity or consumption of an obesogenic diet. Male rats were implanted with intraperitoneal osmotic minipumps, continuously dispensing either saline (control) or lipopolysaccharide (LPS), an endotoxin produced in the gut that triggers inflammation when in circulation. Immunohistochemistry results revealed that LPS exposure led to neuroinflammation, with an increased number of Ionized Calcium-Binding Molecule 1 (Iba1+) cells in the amygdala and hippocampus in LPS rats vs. controls. Given that these brain regions are associated with impulse control, anxiety-like behavior, and learning and memory, we tested whether chronic LPS treatment impacted these behaviors. Interestingly, LPS exposure did not affect hippocampal-dependent memory in the Morris water maze, novel location recognition, or novel object in context memory tests, suggesting that neuroinflammation in the absence of obesity does not induce memory impairments. Further, chronic LPS significantly decreased anxiety-like behavior in the open field test and food impulsivity in an operant-based procedure. LPS animals also had significantly lower corticosterone and melatonin levels when compared to controls, which may contribute to these behavioral outcomes. These results suggest that the low-grade inflammation associated with obesity is not driving obesity-associated memory impairments but does reduce anxiety and food-motivated impulsive responses.

ОПЫТ ПРИМЕНЕНИЯ КОНЦЕНТРАТА ПОЛИФЕНОЛОВ ВИНОГРАДА У ПОЖИЛЫХ ПАЦИЕНТОВ С БРОНХИАЛЬНОЙ АСТМОЙ В ПОСТКОВИДНОМ ПЕРИОДЕ

Состояние лонг-ковида и постковидного синдрома ассоциировано с наличием у пациентов низкоинтенсивного воспаления (НИВ), связанного, в том числе, с нарушением проницаемости естественных барьеров для липополисахарида грамотрицательной флоры. Цель исследования — изучение влияния добавления полифенольного виноградного концентрата к курсу санаторно-курортного лечения у пожилых пациентов с бронхиальной астмой и постковидным синдромом на состояние НИВ, кишечной проницаемости и эндотоксинемии. В исследование были включены 70 пациентов с верифицированным диагнозом бронхиальной астмы, перенесших инфекцию, вызванную вирусом SARSCoV-2. Пациенты были разделены на две группы: 1-я — группа вмешательства (n=40), пациенты которой в дополнение к санаторно-курортному лечению получали концентрат полифенолов винограда; 2-я — контрольная (n=30). Был выполнен ИФА для определения уровня С-РБ, зонулина, липополисахарида, липополисахаридсвязывающего белка и бактерицидного белка, повышающего проницаемость бактерий (BPI). У пациентов 1-й группы выявлено статистически значимое снижение уровня С-РБ (p<0,039) и концентрации циркулирующего липополисахарида (p=0,008). В обеих группах зарегистрировано статистически значимое увеличение концентрации BPI и зонулина (p<0,05). Применение полифенольного концентрата винограда у пожилых пациентов в постковидном периоде снижает уровень С-РБ и циркулирующего эндотоксина крови, что в перспективе должно снизить вероятность отдаленных последствий, связанных с НИВ, в том числе кардиоваскулярных, у пациентов, перенесших новую коронавирусную инфекцию. The state of long-COVID and post-COVID syndrome is associated with the presence of lowgrade inflammation (LGI) in patients, associated, among other things, with impaired permeability of natural barriers for lipopolysaccharide (LPS) of gram-negative flora. Objective — to study the effect of adding polyphenolic grape concentrate to the course of spa treatment in patients with bronchial asthma and post-covid syndrome on the state of LGI, intestinal permeability and edotoxemia. The study included 70 patients with a verified diagnosis of Bronchial asthma who had suffered from infection caused by SARS-CoV-2. Patients were divided into two groups. The intervention group (n=40) received grape polyphenol concentrate in addition to standard spa treatment. Subsequent enzyme-linked immunosorbent assay (ELISA) performed for determination of the levels of C-RP, zonulin, LPS, lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing protein (BPI). In patients of the 1st group a reliable decrease in the level of C-RP (p<0,039) and the concentration of circulating LPS (p=0,008) was revealed. In both groups, a statistically significant increase in the concentration of BPI and zonulin was registered (p<0,05). The use of polyphenolic grape concentrate in elderly patients in the post-covid period reduces the level of C-RP and circulating blood endotoxin, which in the future should reduce the likelihood of long-term consequences associated with NCI, including cardiovascular, in patients who have undergone NCI.

Obesity and Autoimmunity Epidemic: The Role of Immunometabolism.

The relationship between obesity and autoimmune diseases has attracted significant attention in recent years, highlighting the multifaceted connection between metabolic dysregulation and loss of self-immune tolerance. Compelling epidemiological evidence has revealed an elevated prevalence of autoimmune diseases among overweight or obese individuals, suggesting a potential causal link. Mechanistically, adipose tissue is a key immunometabolic organ that secretes an array of adipocytokines that can facilitate proinflammatory immune responses against self-antigens. Indeed, adipose tissue dysfunction in obesity fosters a state of chronic low-grade inflammation, which may contribute to the so-called accelerator hypothesis, in which circulating self-autoreactive T cells can easily lose their regulatory mechanisms, resulting in self-tissue damage and autoinflammation. In this review, we elucidate the intricate immunometabolic pathomechanisms underlying the obesity and autoimmunity epidemic, and we explore innovative therapeutic avenues that could be pivotal for advancing public health initiatives in the context of this epidemic.

The Effect of High-Intensity Functional Training with Thylakoid Supplementation on Anti-Inflammatory Indicators in Obese Men

Background: Obesity is associated with a chronic low-grade inflammatory state related with vascular dysfunction, thrombotic disorders, multiple organ damages, and metabolic dysfunction. To date, no study has examined the effects of different exercise protocols on the profile of inflammatory factors in the body and the use of dietary supplements. The objective of this study was to investigate the effect of 12 weeks of high-intensity functional training (HIFT) with and without thylakoid supplementation on IL-10 and semaphorin-3E levels in obese people. Methods: 44 obese men were randomly assigned to one of four groups: control (C), thylakoid supplementation (T), high-intensity functional training (H), and a combination of supplementation and exercise (HT). The exercise program was performed according to the HIFT protocol for 12 weeks. The thylakoid supplement was extracted from spinach leaves and administered to individuals in the supplement groups. Body mass index (BMI) and biomarkers related to inflammation were measured in the participants' blood samples at the before and after the intervention. Results: In these three groups, H, T, and HT, the levels of the inflammatory factors IL-10, and Semaphorin-3E were compared. In all the three groups, the levels of the anti-inflammatory factor Semaphorin-3E and IL-10 changed significantly (P<0.001 vs. C). The level of Semaphorin-3E exhibited a statistically significant decline in the blood of the H and HT groups who underwent exercise in comparison to the C group (P<0.01) and a significant difference was observed between the exercise training groups, H and HT, and T group (P<0.001). Conclusion: The results of the present study demonstrated that HIFT exercise protocol and the use of thylakoid supplements can reduce systemic inflammatory indicators in obese men. This reduction was observed through a synergistic effect. Consequently, the combination of HIFT exercise and thylakoid supplements represents an effective approach to reducing inflammation in individuals with obesity.

Assessment of Adiposity in Patients with Psoriasis and its Correlation with Disease Severity: A Case-Control Study.

Psoriasis and obesity are known to share many mediators of inflammation with each other such as TNF-α and IL-6. Obesity, being a low-grade inflammatory state, is known to affect the disease course, severity, predisposition, and response to therapy in psoriatic patients. Whole-body dual-energy X-ray absorptiometry (DEXA) is a proven method to estimate total, abdominal, and extremity fat mass. The present study aimed to assess the correlation of the severity of psoriasis with adiposity using regional fat mass DEXA indices. This was a case-control study involving 153 cases followed through till the completion of the study. A total of 153 age and gender-matched controls were included in the study after ruling out confounding factors. DEXA scans were conducted on both cases and controls; the following indices, including total body fat percentage, android-gynoid ratio, and trunk/limb fat mass ratio, were analyzed. The total fat percentage, as assessed by DEXA scan, had a mean of 29.13 ± 9.66 (32.12 ± 9.51 for cases and 26.13 ± 8.87 for controls) with a significant P value of <0.001. The android/gynoid ratio had a mean of 1.01 ± 0.22 (1.09 ± 0.21 for cases and 0.93 ± 0.21 for controls). Percentage fat trunk/percentage fat limbs (central/peripheral fat) had a mean of 1.05 ± 0.16 (1.08 ± 0.15 for cases and 1.03 ± 0.16 for controls) with a significant P value of <0.001. The correlation of DEXA adiposity grading with the severity of psoriasis was found to be significant, with a P value of <0.001. The cross-sectional design restricts assessment to associations rather than causality. Although major confounding factors were ruled out during recruitment, variables such as lifestyle and dietary habits, physical activity levels, and treatment history were not the primary focus and hence not extensively analyzed. The sample size analyses, such as stratification by gender or treatment modalities, may benefit from larger cohorts in future research. DEXA is a useful indicator of adiposity, with greater total fat percentage, android/gynoid ratio, and trunk/limb fat mass ratio in cases compared to controls and it was positively correlated with the severity of psoriasis in our study.

Plasma cytokine levels and PCOS risk: Mendelian randomization analysis reveals IL6R as a preventive factor

BackgroundPolycystic ovary syndrome is a prevalent gynecological condition affecting primarily women of childbearing age. It is characterized by elevated androgen levels, ovulatory dysfunction, and morphological abnormalities. Despite extensive research from various perspectives, the etiology and pathogenesis of PCOS remain unclear. While controversial, many believe that individuals with PCOS exhibit a chronic low-grade inflammatory state. Cytokines play diverse roles in the initiation and progression of inflammation, contributing to this inflammatory milieu. Therefore, the aim of this study was to utilize publicly available genome-wide association study data to explore the potential causal relationship between cytokines and PCOS.MethodsTo accurately investigate the causal relationship between cytokines and PCOS, we initially defined cytokines using the GeneCrad and then identified cytokines in two independent large-scale plasma proteins. Subsequently, we employed a two-sample Mendelian randomization analysis framework. A series of quality control procedures were implemented to select eligible instrumental variables closely associated with the exposure. MR analysis was conducted using genome-wide association studies of PCOS in two independent European ancestry groups. Cochran, s Q test, MR-Egger and intercept test were employed to assess heterogeneity and pleiotropy in PCOS. Co-localization analysis, summary-data-based Mendelian randomization analysis, and HEIDI testing were utilized to further corroborate the relationship between positive findings and PCOS. Finally, systematical Mendelian randomization analysis between healthy lifestyle factors and PCOS-related proteins was conducted to identify which proteins could act as interventional targets by lifestyle changes.ResultsIn our investigation, we performed Mendelian randomization analysis on 33 cytokines in relation to PCOS using data from the deCODE and the Fenland. Our findings revealed that the plasma level of IL6R emerges as a notable protective factor against PCOS, exhibiting a substantial effect size. Moreover, we identified CCL22 as a significant risk factor for PCOS, a finding that was similarly validated and supported by independent cohorts.ConclusionOur Mendelian randomization analysis, leveraging genome-wide association study data from a sizable population cohort, unequivocally delineated a causal relationship between IL6R and PCOS. These results underscore the involvement of cytokines in the pathogenesis of PCOS and highlight their potential as promising therapeutic targets for addressing this intricate disease.

Clinical benefit of immune checkpoint inhibitors in elderly cancer patients: Current evidence from immunosenescence pathophysiology to clinical trial results.

The age-related decline in immunity appears to be associated not only with cancer development but also with differential responses to immune checkpoint inhibitors (ICIs). Despite their increasing utility across various malignancies and therapeutic settings, limited data -derived primarily from subgroup analyses of randomized controlled trials (RCTs), pooled meta-analyses, and retrospective studies- are available on the effects of aging on their efficacy and toxicity. Immunosenescence, characterized by the progressive decline of the function of the immune system, and inflammaging, a state of persistent low-grade sterile inflammation, may influence ICI outcomes. Additionally, the incidence, severity, and subtypes of immune-related adverse events (irAEs) may differ between older and younger individuals due to loss of immunotolerance. In the current review, starting from a a comprehensive discussion of the pathophysiology of immunosenescence, we proceed to critically review age-related retrospective and randomized evidence supporting FDA-approved ICIs. We highlight similarities or differences across age groups and the clinical benefit of ICIs in elderly versus younger cancer patients. The optimal integration of ICIs in geriatric oncology necessitates greater inclusion of this patient demographic in RCTs along with real-world data in order to acquire robust data which will guide evidence-based treatment decisions for this population.

Abstract Th0044: Neutrophils phenotyping and aggregation with platelets: genetic model for atherosclerosis

Neutrophils are major contributors to inflammatory reactions. Neutrophil-platelet interaction is crucial in the development of both cardiac and blood diseases. Neutrophils and platelets interact through adhesion molecules such as L-selectin (CD62L), contributing to thrombosis and inflammation. This interaction plays a key role in cardiovascular diseases like myocardial infarction and atherosclerosis, as well as thrombo-inflammatory diseases. Neutrophils can modulate the function of platelets through secretory molecules leading to a prolonged chronic state of low-grade inflammation. During the course of low-grade inflammation leukocytes infiltrate the vascular endothelium to migrate to the inflamed tissue, platelets can modulate the function of neutrophils by facilitating their migration through disrupted endothelial of blood vessels, this interaction involves the leukocyte adhesion cascade which is critical in the process of trans-endothelial migration, however, there is a gap in our knowledge on how neutrophiles work together with other cells during low-grade inflammation. The balance between the inflammatory response and resolution of neutrophils is crucial to achieve homeostasis in the blood vessels, we hypothesize that neutrophiles use PEX5 peroxisomal transport machinery as a regulatory mechanism to control the inflammatory response. In the present study we used PEX5 knock out mice to examine the response of different neutrophil subsets to LPS and 4-PBA in an in vitro culture model. Purified mouse neutrophils were cultured overnight then cells were harvested and followed by neutrophiles-platelets assay. Our Results showed that the genetic deletion of PEX5 caused neutrophil exhaustion which led to more activation of platelets. By comparing levels of CD11b and CD38 in Pex5+/+ neutrophils and Pex5-/- neutrophils, we found that their levels were higher in Pex5-/- neutrophils, also we found that the level of CD41 was subsequently increased in the Pex5-/- aggregated cells. Taken together, our data reveal that PEX5 may have a potential in the mechanism of regulating the interaction between neutrophiles and platelets in low grade inflammation driven cardiac disease including atherosclerosis.

Anthraquinones and Aloe Vera Extracts as Potential Modulators of Inflammaging Mechanisms: A Translational Approach from Autoimmune to Onco-Hematological Diseases.

Inflammaging is a chronic, low-grade inflammatory state that contributes to age-related diseases, including cardiovascular disorders, osteoporosis, neurodegeneration, and cancer. This process involves immunosenescence, oxidative stress, and immune aging, all of which contribute to the breakdown of immune tolerance and the onset of autoimmune disorders. Aloe vera (AV) has recently gained attention for its immunomodulatory, anti-inflammatory, and antioxidant properties. This review explores the effects of AV extracts and anthraquinones (e.g., aloe-emodin, emodin, aloin) on key inflammaging-driven mechanisms in autoimmunity. Our analysis highlights AV's ability to regulate hormone balance, autoantibody production, and cytokine/chemokine signaling (such as interleukin-1β, tumor necrosis factor-α, and interferon-γ). It modulates inflammatory pathways, including mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), thereby inhibiting nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activation. Additionally, AV enhances antioxidant defenses and restores immune balance by reducing Th1/Th17 subsets while promoting Th2-mediated regulation. Notably, AV also modulates inflammasome-mediated mechanisms and counteracts immunosenescence, which is driven by autophagy-related processes. These effects position AV as a potential integrative approach to mitigating inflammaging-driven autoimmunity. Furthermore, as inflammaging is increasingly recognized in onco-hematological diseases, AV-based strategies may offer novel therapeutic avenues. Future studies should focus on clinical validation, optimizing formulations, and expanding applications to broader age-related and immune-mediated disorders.

Atherosclerosis and Chronic Apical Periodontitis: Systematic Review and Meta-Analysis.

Background: Atherosclerosis is a chronic and progressive condition of the arteries, characterized by the thickening and hardening of their walls due to the formation of atherosclerotic plaques. Low-grade inflammation is implicated in the pathogeny of atherosclerosis. Chronic apical periodontitis (CAP), the chronic inflammation around the root apex of infected teeth, is associated with a low-grade inflammatory state, and thus a connection between atherosclerosis and CAP has been suggested. The aim of this study was to conduct a systematic review with meta-analysis to answer the following PICO question: In adult patients, does the presence or absence of atherosclerosis affect the prevalence of CAP? Methods: The PRISMA guidelines were followed to carry out this systematic review, which was registered in PROSPERO (651359). A bibliographic search was performed in PubMed-MEDLINE, Embase, and Scielo. The inclusion criteria selected studies presenting data on the prevalence of CAP in patients diagnosed with atherosclerosis and control patients. The statistical analysis was carried out using RevMan software v.5.4. The study characteristics and risk ratios with 95% confidence intervals (CIs) were extracted. Random-effects meta-analyses were performed. Risk of bias was assessed using the Newcastle-Ottawa scale, which was adapted for cross-sectional studies. To estimate variance and heterogeneity between trials, the Higgins I2 test was used. The quality of the evidence was evaluated using GRADE. Results: The search strategy recovered 102 articles, and only five met the inclusion criteria. Meta-analysis showed an overall OR = 2.94 (95% CI = 1.83-4.74; p < 0.01) for the prevalence of CAP among patients with atherosclerosis. The overall risk of bias was moderate. The quality of the evidence showed a low level of certainty. Conclusions: Patients with atherosclerosis are almost three times more likely to have CAP. This finding supports the hypothesis that chronic inflammatory processes in the oral cavity could significantly impact cardiovascular health, emphasizing the importance of an integrated approach to oral and systemic health care. This result should be translated to daily clinical practice, and the healthcare community should be aware of this association and suspect atherosclerotic pathology in patients who show a high prevalence of CAP. Likewise, patients with atherosclerosis should be monitored in the dental clinic for CAP.

Endocan Levels and Early Onset Childhood Obesity in Term Infants Born to Mothers with Obesity

Introduction: Maternal obesity induces a physiologic state of chronic low-grade inflammation with elevated levels of circulating inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α that has been linked to various negative long-term outcomes in offspring, such as cardiovascular disease, metabolic syndrome, and obesity. However, this epidemic also impacts pregnancy itself and significantly increases the risk of maternal morbidity and mortality. In the United States, obesity in pregnant women has risen dramatically, with prevalence ranging from 10 to 35%. The number of overweight adults worldwide has now surpassed one billion, and according to the World Health Organization (WHO), 160 million children and adolescents were obese in 2022, including 65 million females and 95 million males. Furthermore, several human and animal studies demonstrate that the intrauterine environment plays a critical role in programming future body composition. Endothelial dysfunction has been measured in infants born to mothers with obesity, specifically with Endocan, a proteoglycan expressed by vascular endothelial cells. This relatively new biomarker is associated with inflammation and dysfunction in the endothelium. Maternal obesity and a high-fat diet have been shown to have deleterious effects through fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Infant levels of Endocan at birth can be an important marker in predicting outcomes in affected infants. We have demonstrated that preterm infants (&lt;33 weeks gestation) with high levels of Endocan at birth are at a higher risk of early-onset childhood obesity (one to two years of age). This study aims to identify an association between cord blood Endocan levels and early onset childhood obesity in term infants. We hypothesize that elevated Endocan at birth is associated with a higher BMI in the early childhood period. Methods: Over an 18-month period, we prospectively enrolled 148 term infants, 92 of which have reached one year of age for this preliminary analysis. Endocan arterial cord blood was drawn at birth and processed without knowledge of maternal history. All births resulted from uncomplicated pregnancies, with all infants being admitted to the normal newborn nursery. Our investigation focused on the infant’s birth weight and BMI percentiles and their growth patterns at six-, nine-, and twelve-month well-child visits. We also analyzed the average grams gained per day from the six-month visit to the twelve-month visit. We used a BMI at 95th percentile as the cutoff for childhood obesity, and comparisons were established using the Mann Whitney U test. Results: Using umbilical cord arterial Endocan level as our biomarker in predicting early onset childhood obesity in term infants, we did not find statistically significant results for BMI percentiles at six-, nine-, and twelve-month well-child visits (p=0.758 at six months, p=0.239 at nine months, and p=0.651 at twelve months). Conclusion: Our results indicate that the vulnerable preterm infants in our previous study (&lt;33 weeks gestation) are perhaps more susceptible to fetal programming compared to term infants. Despite a significant correlation between Endocan and childhood obesity in a preterm cohort, the negative findings in this term cohort study will continue to be investigated. It is important to note that a significant number of study patients have not yet reached two years of age, which may be more optimal to determine trends in obesity. Data assessing childhood BMI at later stages of life could be associated with more significant findings and further support Endocan as a biomarker for early-onset childhood obesity. Our results have the potential to suggest that fetal programming of body composition might have a later onset i.e., two to three years of age in term infants.

Effect of caloric restriction with probiotic supplementation on body composition, quality of life, and psychobiological factors of obese men: A randomized, double-blinded placebo-controlled clinical trial.

Effect of caloric restriction with probiotic supplementation on body composition, quality of life, and psychobiological factors of obese men: A randomized, double-blinded placebo-controlled clinical trial.

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.