Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are in vitro experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.

While occupational exposure as a firefighter is considered a dangerous occupation, research on the underlying mechanisms remains limited, particularly in wildland firefighters. Inflammation, a key effect of wildfire exposure, plays a significant role in the development of various diseases. The current study aims to investigate the impact of wildland firefighting exposure on the levels of pro-inflammatory systemic biomarkers. A pre-post study design investigated 59 wildland firefighters comparing data collected after participation in a wildfire event (Phase II) with data obtained before wildfire season (Phase I). Data on demographics, lifestyle, health and occupational-related factors were assessed. Exposure factors, such as fire combat (e.g., exposure duration), were also registered. Inflammatory biomarkers (i.e. interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor α [TNF-α] and high-sensitivity C-reactive protein [hs-CRP]) and hydroxylated polycyclic aromatic hydrocarbons metabolites (1-OHNaph+1-OHAce, 2-OHFlu, 1-OHPhen, 1-OHPyr) were analysed in blood and urine samples, respectively. Serum IL-8 and IL-6 levels were significantly increased after wildland fire combat. IL-8 levels were 2.62 times higher (95 % CI: 1.96-3.50; p < 0.01), whereas IL-6 levels were 1.25 times higher (95 % CI: 1.00-1.57; p = 0.04). Furthermore, IL-8 levels were significantly correlated with urinary 2-hydroxyfluorene levels and fire combat duration (>12 h). In addition, the mean hs-CRP level, in both phases, was above 3.0 mg/L, indicating a potential risk for cardiovascular events. Given the long-term health implications of firefighting occupational exposure, biomonitoring and early detection of occupational risks are essential for protecting firefighters' health. Protective measures must be urgently implemented to enhance occupational health and strengthen preventive strategies in this sector.

The global obesity epidemic highlights the need to understand the molecular mechanisms that regulate energy metabolism. Among emerging research areas, fat browning-the transformation of white adipose tissue into beige fat-has gained significant attention. This review explores the molecular pathways involved in fat browning triggered by fasting, physical exercise, and cold exposure, emphasizing both shared and distinct regulatory mechanisms. These stimuli consistently induce physiological responses such as lipolysis, mitochondrial biogenesis, and improved insulin sensitivity. Notably, PGC-1α and SIRT3 are upregulated across all three conditions, underscoring their central roles in mitochondrial function and energy metabolism and identifying them as promising therapeutic targets. In contrast, UCP1 and PRDM16 exhibit condition-specific regulation, suggesting they may not be universally essential for fat browning. In addition, the review discusses species-specific differences in brown adipose tissue (BAT) activation, particularly between rodents and humans, highlighting the challenges of translating animal model findings to human therapies. Future research should aim to develop selective pharmacological activators of PGC-1α and SIRT3 to enhance therapeutic outcomes while minimizing adverse effects. This review also proposes that integrating fasting, exercise, and cold exposure could provide innovative strategies to promote metabolic health.

Individuals with low sexual frequency often experience comorbidities that exacerbate mortality. This article evaluates the predictive value of five body fat anthropometric indicators for all-cause mortality and explores the interaction between obesity and depression in mortality among young and middle-aged individuals with sexual frequency <12 times per year.

This study included participants with a sexual frequency of <12 times per year from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). We assessed the impact of anthropometric indicators and depression on mortality, as well as their synergistic interactions, and further developed an accessible predictive survival model.

A total of 4978 participants aged 20-59 were included, with 215 deaths (4.3 %) over 15 years of follow-up. A Body Shape Index (ABSI) showed the strongest association with all-cause mortality, with an AUC of 0.67. Participants with ABSI ≥0.082 had a significantly higher risk of death (HR: 1.87, 95%CI: 1.31-2.68), as did those with depression (HR: 1.86, 95%CI: 1.19-2.92). Interaction analysis revealed a synergistic effect between depression and ABSI, increasing death risk by 293 % when both were present. Significant survival differences were observed between men and women with these risk factors, with median survival rates of 76.3 % and 90.8 %, respectively. The model based on ABSI and depression provided valuable mortality predictions, with AUC of 0.78, 0.77, and 0.77 for 3-year, 5-year, and 10-year survival.

ABSI and depression are associated with all-cause mortality in individuals with low sexual frequency, potentially creating a synergistic effect on mortality risk.

Epithelial V-like antigen 1 (Eva1) is a highly specific marker for brown adipose tissue (BAT) in both mice and humans, but its metabolic function remains unclear. We investigated the impact of Eva1 deletion on the development of obesity.

To assess the metabolic role of Eva1, we generated whole-body and adipocyte-specific Eva1knockout (KO) mice, which were subjected to a high-fat diet (HFD) for 12 weeks and characterized metabolic phenotypes. To further elucidate the depot-dependent impact of Eva1 deficiency, we performed histological analysis and 3' mRNA-seq of BAT and epididymal visceral white adipose tissue (eWAT). To investigate the role of macrophage-derived Eva1 in obesity development, we transplanted wild-type (WT) or Eva1KO macrophages into Eva1KO mice fed an HFD.

We found that whole-body Eva1KO mice are resistant to HFD-induced obesity, insulin resistance and visceral adipose inflammation. However, Eva1 deletion in adipocytes, both brown and white, did not phenocopy these protective effects. Notably, whole-body Eva1 deficiency triggers functional changes in eWAT, but not in BAT. These results led us to investigate a possible involvement of macrophages in Eva1-mediated obesity regulation. We found that Eva1 is expressed in macrophages and plays a role in lipopolysaccharide (LPS)-induced inflammatory responses, possibly through the direct interaction with toll-like receptor 4 (TLR4). Moreover, Eva1KO mice exhibited improved survival rates in the face of severe sepsis induced by LPS. Importantly, transplantation of WT macrophages to Eva1KO mice abolished the beneficial effects of whole-body Eva1 deletion against obesity and visceral adipose inflammation.

Our findings highlight macrophage-derived Eva1 as an important mediator in obesity-induced eWAT remodeling, suggesting that targeting Eva1 could offer a novel therapeutic strategy for obesity-related metabolic disorders.

This study endeavors to unveil the association between the Metabolic Score for Insulin Resistance (METS-IR) and stroke among adults utilizing data of the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS), and whether oxidative stress (OS) mediates their association.

Our study cohort comprised 101,316 individuals from NHANES and 17,708 individuals from CHARLS. The intricate relationships among the METS-IR, stroke, and OS biomarkers were evaluated via logistic regression, restricted cubic splines (RCS), as well as mediation analysis.

The final analysis included 22,542 American and 9521 Chinese participants, among whom 844 and 887 were diagnosed with stroke, respectively. Regression analysis indicated a positive association of METS-IR with stroke [NHANES: OR = 1.01, 95 % CI (1.01, 1.02), p < 0.001; CHARLS: OR = 1.02, 95 % CI (1.02, 1.03), p < 0.001], with higher METS-IR quartiles being associated with elevated stroke incidence [NHANES: OR = 1.39, 95 % CI (1.11, 1.73), p = 0.004; CHARLS: OR = 1.74, 95 % CI (1.39, 2.17), p < 0.001]. Participants with elevated METS-IR and serum uric acid (SUA) exhibited the greatest probability of stroke. Mediation analysis proved that OS partially mediated this association [Mediation effect: NHANES β = -8.45e-5, 95 % CI (-1.41e-4, -4.01e-5), p < 0.001; CHARLS β = -4.02e-5, 95 % CI (-8.14e-5, -7.76e-6), p = 0.012].

The METS-IR was positively associated with stroke in NHANES and CHARLS cohorts, and OS partially mediated this association.

Two common non-communicable diseases, obesity and periodontitis, are responsible for and affected by systemic inflammation, sharing common risk factors and mechanistic pathways. Periodontitis is an irreversible immune-mediated inflammatory disease of hard and soft tissue supporting teeth. If left untreated, periodontitis can lead to tooth loss, affecting food choices and healthy eating, therefore affecting overall health. Obesity is an independent predictive factor for worsened periodontal inflammation, increased onset, progression, severity, and recurrence of infection, as well as delayed wound healing. Thus, managing obesity and associated metabolic dysfunctions may improve periodontal therapy outcomes. The chronic inflammatory state of obesity impairs immune regulation exacerbating the inflammatory gingival tissue destruction of periodontitis, which can also systemically contribute to inflammatory mediators. Furthermore, bariatric surgeons and dietitians should educate patients with obesity regarding the risk of elevated caries, xerostomia, and periodontitis risk from acid reflux and frequent food intake. Non-dental healthcare professionals should recognise periodontal disease signs to prompt dental referral when warranted. Asking patients about recent dental visits promotes patient involvement in cross-discipline dialogue to enhance patient care coordination between medicine and dentistry. This article discusses the association between these two diseases, the challenges of achieving optimal periodontal treatment outcomes, and the clinical strategies to enhance holistic care. It also explores oral health considerations in dietary and surgical interventions in the treatment of obesity.

Mitochondria, as central regulators of cellular processes such as energy production, apoptosis, and metabolic homeostasis, are essential to cellular function and health. The maintenance of mitochondrial integrity, especially through mitophagy-the selective removal of impaired mitochondria-is crucial for cellular homeostasis. Dysregulation of mitochondrial function, dynamics, and biogenesis is linked to neurodegenerative and metabolic diseases, notably Alzheimer's disease (AD), which is increasingly recognized as a metabolic disorder due to its shared pathophysiologic features: insulin resistance, oxidative stress, and chronic inflammation. In this review, we highlight recent advancements in pharmacological interventions, focusing on agents that modulate mitophagy, mitochondrial uncouplers that reduce oxidative phosphorylation, compounds that directly scavenge reactive oxygen species to alleviate oxidative stress, and molecules that ameliorate amyloid beta plaque accumulation and phosphorylated tau pathology. Additionally, we explore dietary and lifestyle interventions-MIND and ketogenic diets, caloric restriction, physical activity, hormone modulation, and stress management-that complement pharmacological approaches and support mitochondrial health. Our review underscores mitochondria's central role in the pathogenesis and potential treatment of neurodegenerative and metabolic diseases, particularly AD. By advocating for an integrated therapeutic model that combines pharmacological and lifestyle interventions, we propose a comprehensive approach aimed at mitigating mitochondrial dysfunction and improving clinical outcomes in these complex, interrelated diseases.

This review aims to provide a comprehensive overview to understand the role of pollution in the development of noncommunicable diseases (NCDs), with a focus on metabolic diseases.

In the context of NCDs, the incidence of metabolic diseases such as obesity and diabetes are increasing at an alarming rate. In addition to the well-known role of the so-called "obesogenic" environment, characterized by unhealthy diet and physical inactivity, great attention has been paid in recent years to the effects of pollution. Indeed, progressive urbanization has been associated with increased exposure to pollutants. The harmful effects of some pollutants on the endocrine system have been known for decades, but data on the metabolic impact of pollution are rather recent. Pollution in its various forms promotes a systemic inflammatory state, insulin resistance, and oxidative stress, which appear to be closely associated with increased risk of NCD, particularly obesity and diabetes.

In conclusion, urbanization has so far had a predominantly negative impact on collective health, but a better understanding of the mechanisms linking pollution to metabolic health is crucial to implement preventive strategies, including careful urban planning to improve community health, understood not only as the absence of disease but also as psychological and social well-being, overcoming the risks associated with urbanization.

MAFLD is highly prevalent among overweight and obese individuals. Recently, the American Heart Association proposed a new measure of cardiovascular health (Life's Essential 8). This study investigated the relationship between the Life's Essential 8 (LE8) and MAFLD, all-cause and cardiovascular mortality in these populations, exploring the mediating role of inflammation and insulin resistance. This retrospective study used data from the National Health and Nutrition Examination Survey (NHANES, 2007-2018), including 6,885 overweight and obese individuals. LE8 scores were categorized into low, medium, and high groups. Weighted logistic regression and Cox proportional hazards models assessed the relationships between LE8, MAFLD, and mortality. Mediation analyses explored the roles of inflammation and insulin resistance, and weighted restricted cubic spline (RCS) regression examined potential nonlinear associations. Kaplan-Meier survival analysis evaluated survival rates across LE8 groups, and subgroup analyses assessed interactions with demographic characteristics. Additionally, ROC curves were used to explore the predictive accuracy of various inflammation and insulin resistance biomarkers. In model 3, compared to the low LE8 group, the prevalence of MAFLD in the highest LE8 group was reduced by 89% (OR = 0.11; 95% CI: 0.06, 0.20). HOMA-IR mediated 72.26% of the mediation effect. Various inflammation markers, including CRP, hs-CRP, SII, and SIRI indices, mediated effects ranging from 3 to 12%. Compared to the low LE8 group, the highest LE8 group had a 58% reduction in all-cause mortality and a 90% reduction in cardiovascular mortality. Kaplan-Meier analysis showed that the higher LE8 groups had significantly higher survival rates than the low LE8 group. Inflammatory markers mediated 5-17% of the mediation effects. Restricted cubic spline (RCS) curves revealed a non-linear relationship between LE8 and MAFLD. Age interacted with LE8 in several subgroup analyses. ROC curves showed that HOMA-IR had strong predictive accuracy for MAFLD, while SIRI demonstrated potential advantages in predicting mortality risk. In overweight/obese populations, LE8 scores were negatively associated with the prevalence of MAFLD, and risk of mortality. These findings emphasize the importance of maintaining high levels of LE8 scores for primary prevention in overweight/obese populations.

Obesity is associated with an increased risk of cardiometabolic morbidity and mortality, which may be attributable to systemic low-grade inflammation. The impact of bariatric surgery-induced weight loss on low-grade inflammation has not yet thoroughly been described. We investigated the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the plasma levels of cytokines, chemokines, and cytokine receptors prior to surgery (baseline), and then three and 12 months after surgery.

We recruited 68 individuals (41 females, 27 males) with severe obesity (42.84 ± 6.28) who had been referred for bariatric surgery (RYGB: n = 29, SG: n = 39). Blood samples were collected after an overnight fast at baseline (immediately before surgery), 3 and 12 months after surgery. Eleven patients without obesity or cardiometabolic disease served as controls at baseline. Ninety-two plasma proteins were measured using an Olink Target 96 inflammation panel.

We used a linear mixed model to test differences in inflammatory markers at baseline, across time points and between groups. At baseline, 36 cytokines were found to be differentially expressed between the bariatric surgery patients and controls. Of these cytokines, 13 had significantly decreased three months after bariatric surgery and 27 had significantly decreased 12 months after surgery, compared with baseline. Two cytokines (CCL25 and CCL28) increased markedly after 12 months. Only one cytokine (CCL25) was significantly different between the procedures performed, where it increased in the RYGB group 12 months after surgery.

Individuals with severe obesity have increased expression of plasma inflammatory cytokines compared to controls, but low-grade inflammation improves following bariatric surgery, regardless of whether it is RYGB or SG.

Termitomyces mushrooms exhibit a wide range of beneficial properties, yet detailed structural characterization and exploration of their structure-activity relationships, particularly in the anti-obesity contexts, remain limited. A novel galactoglucomannan (TIP-1-1) was isolated from Termitomyces intermedius. Structural analysis showed TIP-1-1 is a 2.7kDa polysaccharide mainly composed of glucose, galactose and mannose (mass ratio: 75.7: 10.7: 13.6). The backbone contained linear 1,6-linked β-Glcp, 1,3-linked β-Glcp, 1,6-linked α-Galp, and 1,3,6-linked α-Manp contained a branched structure that substituted primarily with 1,3,6-linked α-Manp and 1,3-linked β-Glcp residues. Functionally, TIP-1-1 mitigated HFD-induced obesity in mice by reducing body weight, fat mass, and improving glucose homeostasis and lipid profiles, with effects comparable to GLP-1. It suppressed pro-inflammatory cytokines such as NO, TNF-α, IL-6, IL-1β, leptin and restored adiponectin and IL-10 levels both in vivo and in vitro, suggesting anti-inflammatory mechanisms underlying its anti-obesity effects. In lipid metabolism studies, TIP-1-1 inhibited adipocyte lipogenesis by activating AMPK, suppressing the expression of ACC and FASN, and reducing triglyceride accumulation. Mechanistically, AMPK siRNA knockdown abolished these effects, confirming its central role in TIP-1-1-mediated suppression of de novo fatty acid synthesis. These findings established TIP-1-1 as a dual-acting anti-obesity agent with therapeutic potential via anti-inflammatory and AMPK/ACC/FASN lipogenic inhibition.

Immune system plays a crucial role in the physiological and pathological regulation of the cardiovascular system. The exploration history and milestones of immune system in cardiovascular diseases (CVDs) have evolved from the initial discovery of chronic inflammation in atherosclerosis to large-scale clinical studies confirming the importance of anti-inflammatory therapy in treating CVDs. This progress has been facilitated by advancements in various technological approaches, including multi-omics analysis (single-cell sequencing, spatial transcriptome et al.) and significant improvements in immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate and adaptive immunity holds a pivotal role in CVDs, involving Toll-like receptor (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2) signaling pathway, inflammasome signaling pathway, RNA and DNA sensing signaling pathway, as well as antibody-mediated and complement-dependent systems. Meanwhile, immune responses are simultaneously regulated by multi-level regulations in CVDs, including epigenetics (DNA, RNA, protein) and other key signaling pathways in CVDs, interactions among immune cells, and interactions between immune and cardiac or vascular cells. Remarkably, based on the progress in basic research on immune responses in the cardiovascular system, significant advancements have also been made in pre-clinical and clinical studies of immunotherapy. This review provides an overview of the role of immune system in the cardiovascular system, providing in-depth insights into the physiological and pathological regulation of immune responses in various CVDs, highlighting the impact of multi-level regulation of immune responses in CVDs. Finally, we also discuss pre-clinical and clinical strategies targeting the immune system and translational implications in CVDs.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition closely associated with metabolic syndrome and linked to circadian disruptions. Circadian Syndrome (CircS), a constellation of metabolic and circadian dysregulations, has emerged as a risk factor for metabolic disorders. This study aims to examine the association between CircS and MASLD and to evaluate the potential relevance of CircS in identifying individuals at elevated MASLD risk.

Data from 2,288 participants in the 2017-2018 U.S. National Health and Nutrition Examination Survey (NHANES) cycle were analyzed. Weighted logistic regression models were used to assess the overall association between CircS and MASLD. Restricted cubic spline (RCS) analyses were applied to evaluate the dose-response relationship. Subgroup analyses were conducted to explore potential effect modifiers underlying the CircS-MASLD association.

A significant association between CircS and MASLD was observed. Application of weighted logistic regression revealed that individuals with CircS had increased odds of MASLD (adjusted OR = 4.123, 95% CI: 2.489-6.832, P = 0.001) after adjusting for demographic, lifestyle, and metabolic covariates. The association was consistent across demographic subgroups, with a linear trend showing higher CircS scores correlating with increased MASLD risk.

CircS is significantly associated with MASLD and may have potential implications for early risk identification and targeted intervention. However, its clinical utility requires further validation in prospective studies before integration into routine practice.

Obesity, a main driver of cardiovascular morbidity, contributes to endothelial dysfunction and inflammation in adipose tissues. Perivascular adipose tissue (PVAT) surrounds arteries and influences vascular function. In obesity, immune cells, including myeloperoxidase (MPO)-releasing myeloid cells, accumulate in PVAT. In this study, we show MPO levels to correlate with body weight and endothelial function in obese patients (n = 33) and mice. In addition, MPO deficiency reduces immune cell frequency, enhances PVAT beiging via soluble guanylyl cyclase β1 (sGC-β1), and increases oxygen consumption in vivo. Further, nitrotyrosine formation and inflammatory cytokine release are attenuated in obese Mpo-/- mice. Mechanistically, adiponectin (APN) secretion improves endothelial function and reduces arterial stiffness. In vitro, MPO-treated human white adipocytes show lower APN and brown adipocyte marker expression but increased inflammation. Thus, MPO impairs vascular function via PVAT inflammation and suppression of vasoprotective mediators, making it a potential therapeutic target in obesity-related cardiovascular disease.

To determine the associations of body mass index (BMI) and waist circumference (WC) with severe diabetic complications in patients with type 2 diabetes.

In total, 114 254 participants with type 2 diabetes (82% male; mean age, 52.52 ± 8.27 years; median follow-up, 4.64 years) were enrolled from a nationwide Japanese medical claims database. Cox proportional models with multivariate adjustment were used to assess the associations of BMI and WC with treatment-requiring diabetic eye disease (TRDED), initiation of dialysis, coronary artery disease (CAD), cerebrovascular disease (CVD), heart failure (HF) and amputation.

BMI was inversely associated with TRDED, especially in women. Men with WC ≥ 95 cm had a significantly lower risk of TRDED (hazard ratio [HR] = 0.79, 95% CI = 0.69-0.91). Dialysis initiation displayed L-shaped associations with BMI and WC. The risk of CAD was significantly reduced among men with BMI < 20.0 kg/m2 (HR = 0.68, 95% CI = 0.49-0.94). HF had U-shaped associations with BMI and WC. Abdominal obesity increased CVD risk (HR = 1.36, 95% CI = 1.08-1.70). BMI ≥ 25 kg/m2/WC ≥ 90 cm significantly reduced the risk of dialysis (HR = 0.42, 95% CI = 0.29-0.62) and increased the risk of HF (HR = 1.33, 95% CI = 1.03-1.72).

BMI/WC had both positive and negative associations with diabetic complications. Therefore, each patient's BMI/WC target should be carefully determined for each diabetic complication, considering the risk of developing other diseases.

The treatment landscape of non-small-cell lung cancer (NSCLC) is evolving rapidly, driven by advances in the development of targeted agents and immunotherapies. Despite this progress, some patients have suboptimal responses to treatment, highlighting the need for new therapeutic strategies. In the past decade, the important role of the tumour microenvironment (TME) in NSCLC progression, metastatic dissemination and response to treatment has become increasingly evident. Understanding the complexity of the TME and its interactions with NSCLC can propel efforts to improve current treatment modalities, overcome resistance and develop new treatments, which will ultimately improve the outcomes of patients. In this Review, we provide a comprehensive view of the NSCLC TME, examining its components and highlighting distinct archetypes characterized by spatial niches within and surrounding tumour nests, which form complex neighbourhoods. Next, we explore the interactions within these components, focusing on how inflammation and immunosuppression shape the dynamics of the NSCLC TME. We also address the emerging influences of patient-related factors, such as ageing, sex and health disparities, on the NSCLC-TME crosstalk. Finally, we discuss how various therapeutic strategies interact with and are influenced by the TME in NSCLC. Overall, we emphasize the interconnectedness of these elements and how they influence therapeutic outcomes and tumour progression.

Pancreatic cancer is characterized by late diagnosis, therapy resistance, and poor prognosis, necessitating the exploration of early carcinogenesis and prevention methods. Preclinical mouse models have evolved from cell line-based to human tumor tissue- or organoid-derived xenografts, now to humanized mouse models and genetically engineered mouse models (GEMMs). GEMMs, primarily driven by oncogenic Kras mutations and tumor suppressor gene alterations, offer a realistic platform for investigating pancreatic cancer initiation, progression, and metastasis. The incorporation of inducible somatic mutations and CRISPR-Cas9 screening methods has expanded their utility. To better recapitulate tumor initiation triggered by inflammatory cues, common pancreatic risk factors are being integrated into model designs. This approach aims to decipher the role of environmental factors as secondary or parallel triggers of tumor initiation alongside oncogenic burdens. Emerging models exploring pancreatitis, obesity, diabetes, and other risk factors offer significant translational potential. This review describes current mouse models for studying pancreatic carcinogenesis, their combination with inflammatory factors, and their utility in evaluating pathogenesis, providing guidance for selecting the most suitable models for pancreatic cancer research.

Background/Objectives: Endoplasmic reticulum stress (ERS) contributes to hepatocyte inflammation, triggered by prolonged exposure to lipotoxicity, and promotes non-alcoholic fatty liver disease (NAFLD) progression by recruiting and activating hepatic macrophages, which accelerate fibrosis and exacerbate disease progression. Here, we aimed to evaluate the therapeutic potential of ginsenoside Rh2 (Rh2) in a cell model of NAFLD induced by the ERS inducer thapsigargin (THA). Methods: HepG2 cells were treated with THA to induce ERS and mimic NAFLD conditions. The effects of Rh2 on ERS, lipid accumulation, and apoptosis were assessed in HepG2 cells. Additionally, THP-1 cells were used to investigate macrophage activation upon exposure to conditioned medium (CM) from THA- and Rh2-treated HepG2 cells. Gene and protein expression of inflammatory and lipid synthesis markers were analyzed, as well as M1/M2 macrophage polarization markers. Results: Rh2 inhibited THA-induced apoptosis, ERS, and lipid accumulation in HepG2 cells. It also reduced the expression of lipid synthesis genes (SREBF1, FAS) and inflammatory markers (IL-6, IL-1β, TNF-α, MCP-1). CM from Rh2-treated HepG2 cells suppressed macrophage activation in THP-1 cells, decreased M1 polarization markers (CD80, CD86), and increased M2 markers (CD163, Arg1, MRC-1). Conclusions: These results suggest that Rh2 effectively suppresses inflammation and lipid storage in ERS-induced HepG2 cells while modulating the crosstalk between hepatocytes and macrophages. These findings underscore the potential of Rh2 as a promising therapeutic agent for the prevention and early intervention of NAFLD progression.

Most forms of obesity are associated with chronic diseases that remain a global public health challenge.

Despite significant advancements in understanding its pathophysiology, effective management of obesity is hindered by the persistence of knowledge gaps in epidemiology, phenotypic heterogeneity and policy implementation.

This consensus statement by the European Society for Clinical Investigation identifies eight critical areas requiring urgent attention. Key gaps include insufficient long-term data on obesity trends, the inadequacy of body mass index (BMI) as a sole diagnostic measure, and insufficient recognition of phenotypic diversity in obesity-related cardiometabolic risks. Moreover, the socio-economic drivers of obesity and its transition across phenotypes remain poorly understood.

The syndemic nature of obesity, exacerbated by globalization and environmental changes, necessitates a holistic approach integrating global frameworks and community-level interventions. This statement advocates for leveraging emerging technologies, such as artificial intelligence, to refine predictive models and address phenotypic variability. It underscores the importance of collaborative efforts among scientists, policymakers, and stakeholders to create tailored interventions and enduring policies.

The consensus highlights the need for harmonizing anthropometric and biochemical markers, fostering inclusive public health narratives and combating stigma associated with obesity. By addressing these gaps, this initiative aims to advance research, improve prevention strategies and optimize care delivery for people living with obesity.

This collaborative effort marks a decisive step towards mitigating the obesity epidemic and its profound impact on global health systems. Ultimately, obesity should be considered as being largely the consequence of a socio-economic model not compatible with optimal human health.

Chronic inflammation is a hallmark for Metabolic Syndrome (MetS). It is also one of the most important risk factors for insulin resistance and metabolic disorders. Inflammasomes, which are intracellular multiprotein complexes within the innate immune system, regulate the production and maturation of pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18 upon sensing pathogens or danger signals in the cytosol. A growing body of evidence indicates that inflammasomes play a pivotal role in the pathophysiology and progression of metabolic diseases, as deficiency in the key component of inflammasomes protects mice from high fat diet induced obesity and insulin resistance. Thus, in this review, we will summarize the role of inflammasomes in MetS and how to treat MetS by targeting inflammasomes. This may provide novel insights and therapeutic targets for treating metabolic disorders.

Emerging studies suggest obesity may improve PD-1/PD-L1 inhibitor efficacy, correlating with prolonged survival, known as the 'obesity paradox'. However, the impact of this paradox and obesity-related chronic inflammation on immunotherapy for advanced gastric cancer (AGC) has not received sufficient research.

Between January 2018 and December 2021, patients receiving neoadjuvant therapy were categorized into two groups: combined immunotherapy (ICIs, n = 173) and neoadjuvant chemotherapy (NAC, n = 126). Visceral (VATI) and subcutaneous adipose tissue index (SATI) were obtained from pre-treatment CT images. The systemic immune-inflammation index (SII) was calculated as platelet count multiplied by the neutrophil-to-lymphocyte ratio.

The median age of patients was 64 years (IQR 56-69), with 219 (73.2%) males and 80 (26.8%) females. In the ICIs group, the VATI-High group showed significantly higher 3-year overall survival (OS) (p = 0.010) and disease-free survival (DFS) (p = 0.029). Similar results were observed in the SATI analysis (p < 0.05). Conversely, OS (p = 0.040) and DFS (p = 0.039) were significantly lower in the SII-High group. Both VATI and SATI were independent protective factors for OS and DFS, but the effect disappeared after adjustment for SII. SII was associated with poorer OS and DFS, even after adjustment for VATI and SATI. No significant differences were observed in the analysis of the NAC group.

Elevated adiposity indices (VATI/SATI) and low SII correlate with survival benefit in ICI-treated AGC patients, and importantly, this paradoxical survival benefit is dependent on SII status. In contrast, no such benefit is observed in chemotherapy-alone cohorts.

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with dyslipidemia, obesity, diabetes mellitus, and hypertension being major modifiable risk factors. Functional foods with antioxidant and anti-inflammatory properties have gained attention for their potential for reducing CVD risk. Edible bird's nest (EBN), a functional food rich in bioactive compounds such as sialic acid, lactoferrin, and glycoproteins, has been shown to exhibit antioxidant and anti-inflammatory effects. This review explores the potential of EBN in mitigating CVD risk factors, focusing on its role in improving lipid profiles, managing obesity, and enhancing glucose metabolism. EBN has been shown to improve the lipid profile by regulating the hepatic cholesterol metabolism and gut-liver axis interactions. Additionally, EBN reduces body weight gain and visceral fat accumulation, improves adipokine regulation, and enhances insulin sensitivity, which may collectively support cardiovascular health. Despite promising findings, clinical evidence remains limited. Future research should focus on clinical trials to validate its efficacy, determine optimal dosages, and assess its long-term safety. Additionally, further studies on EBN's effects on hypertension and its interaction with conventional therapies could enhance its potential role in CVD prevention and management.

We assessed the associations of visceral adiposity indexes such as Chinese Visceral Adiposity Index (CVAI), Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), waist circumference (WC), and waist-hip ratio (WHR) with overall and specific cancer incidence in a Chinese population.

332,297 individuals from the Taiwan MJ cohort (1996-2007) were included. We utilized multivariable Cox proportional hazards models to examine associations of baseline visceral adiposity indexes and cancer incidences. Sex-specific CVAI, VAI, and LAP were calculated, incorporating WC and triglycerides levels. CVAI and VAI also included body mass index and high-density lipoprotein, with CVAI further incorporating age.

Higher CVAI was consistently associated with higher overall cancer incidence, with HRs of 1.45 (95% CI: 1.2-1.76) and 2.03 (95% CI: 1.52-2.72) for males and females, respectively, comparing the fifth quintile to the first. The HRs for WC were 1.27 (95% CI: 1.08-1.49) and 1.19 (95% CI: 1.01-1.40) for males and females, WHR was significantly associated with cancer risk in males (HR:1.28; 95% CI: 1.13-1.45), and LAP was significantly associated with cancer risk in females (HR: 1.25; 95% CI: 1.04-1.5). VAI was not associated with overall cancer incidence.

CVAI is a superior clinical biomarker for predicting cancer incidence in the Chinese population compared to traditional visceral obesity indices.

Major depressive disorder (MDD) is a leading cause of disability, and chronic inflammation is a contributing factor to its onset and progression. This study examined the relationship between genetic predisposition to inflammation and MDD risk in a nationally representative sample of U.S. military veterans, as well as psychosocial moderators of this association.

A composite polygenic risk score (PRS) for inflammatory biomarkers was derived from the UK Biobank and examined in relation to a positive MDD screen in 1,660 European-American veterans. The analysis adjusted for known correlates of inflammation and MDD, including medical conditions and cumulative trauma burden.

Each standard deviation increase in the inflammatory PRS was associated with more than two-fold increased odds of screening positive for MDD (OR = 2.51, 95% CI = 1.39-4.54). Interaction analyses revealed that optimism moderated this association; among those in the highest PRS tertile, individuals with high optimism were more than 30 times less likely to screen positive for MDD compared to those with low optimism (0.7% vs. 22.6%). Pathway-based analyses identified enrichment of immune- and brain-related gene sets, highlighting potential biological mechanisms linking inflammation and MDD.

Findings suggest genetic risk for inflammation contributes to MDD vulnerability and that optimism may buffer this risk.

The visceral adiposity index (VAI) reliably measures body fat distribution and related dysfunctions. However, its association with sleep disorders among US adults remains unclear.

This study analyzed cross-sectional data from the 2005 to 2018 National Health and Nutrition Examination Survey (NHANES) for adults aged 18 and older. We used multivariable logistic regression to evaluate the association between VAI and sleep disorders and applied restricted cubic splines to assess potential non-linear relationships. Additionally, subgroup analyses by gender, age, and race were conducted to explore the VAI-sleep disorder association across different populations.

This study included 14,021 adults aged 18 +. In Model 1, adjusted for gender and age, each unit increase in VAI was associated with a 5% higher risk of sleep disorders (OR = 1.05; 95% CI = 1.02-1.07). In Model 2, which adjusted for all potential confounders, each unit increase in VAI was linked to a 3% higher risk (OR = 1.03; 95% CI = 1.00-1.05). When treating VAI as a categorical variable, those in the highest quartile (Q4) had a 21% higher risk of sleep disorders compared to those in the lowest quartile (Q1) (OR = 1.21; 95% CI 1.03-1.41). Restricted cubic spline analysis revealed a positive linear relationship between VAI and sleep disorder prevalence. Subgroup analysis found stronger associations in males and non-Hispanic white individuals.

While causality cannot be confirmed, this cross-sectional study shows a significant positive linear association between higher VAI and the risk of sleep disorders among U.S. adults.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening disease with high morbidity and mortality. The triglyceride-glucose (TyG) index, a marker of insulin resistance (IR), has been linked to adverse outcomes in cerebrovascular conditions; however, its influence on functional prognosis in aSAH remains unclear. This study aimed to elucidate the relationship between the TyG index and functional outcomes in aSAH patients.

A retrospective cohort study included consecutive aSAH patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and categorized as favorable (mRS 0-2) or unfavorable (mRS 3-6). Univariate and multivariate logistic regression analyzed the association between the TyG index and functional outcomes. Propensity score matching (PSM) was used to mitigate confounding. Non-linear relationships were explored with restricted cubic splines (RCS), and subgroup analyses were performed. A nomogram integrating the TyG index and traditional prognostic scales was developed, and model predictive performance was compared using the area under the curve (AUC) on a test set.

A total of 470 patients (61.7% female) were enrolled, with 154 experiencing unfavorable outcomes. Multivariate logistic regression showed a significant association between the TyG index and adverse outcomes (OR: 1.86, 95% CI 1.12-3.1, P = 0.017). An optimal TyG index cutoff of 8.83 was identified. Patients with TyG index ≥ 8.83 had a higher risk of poor outcomes (48.7% vs. 24.8%; P = 0.015). PSM confirmed these findings. RCS indicated a progressive association between elevated TyG index and increased risk of adverse functional outcome. Subgroup analyses showed consistent relationships. The enhanced model with the TyG index had a higher AUC (0.899) than the traditional model (0.889, DeLong test P = 0.048).

A high TyG index is significantly associated with an increased risk of unfavorable functional outcomes in patients with aSAH.

The gut microbiome influences physiological responses to exercise by modulating inflammatory markers and metabolite production. Athletes typically exhibit greater microbial diversity, which may be associated with improved performance, but the mechanisms linking different exercise modalities to the gut microbiome are not fully understood. In this study, blood and stool samples were collected from endurance athletes, strength athletes, and non-athletic controls performing two maximal exercise tests (the anaerobic Wingate test and the aerobic Bruce Treadmill Test) to integrate serum biomarker data with gut bacterial metagenomic profiles. While most biochemical markers showed similar post-exercise trends across groups, SPARC (secreted protein acidic and rich in cysteine) and adiponectin levels showed modality-specific responses. Strength-trained participants showed unique microbiome-biomarker associations after the Wingate test. In addition, baseline enrichment of certain bacterial taxa, including Clostridium phoceensis and Catenibacterium spp., correlated with reduced Bruce Treadmill test response in strength-trained individuals. These findings, while requiring further validation, indicate the complex interplay between exercise type, training background, and the gut microbiome, and suggest that specific microbial species may help shape recovery and adaptation.

Metabolic syndrome (MetS) is a disease with complex and diverse etiologies. Extrinsic factors such as diet and lifestyle can induce dysbiosis of gut microbes, compromising intestinal barrier integrity and leading to inflammation and insulin resistance, thereby advancing MetS. Probiotic interventions have shown potential in ameliorating gut microbiota dysbiosis and regulating host metabolism by assimilating lipids, metabolizing carbohydrates, and producing short-chain fatty acids (SCFA), indole compounds, secondary bile acids, conjugated linoleic acid (CLA), and other active ingredients. An increasing number of new strains are being isolated and validated for their effective roles intervening on MetS in animal and population studies. This review aims to provide updated insights into the pathogenic mechanisms of MetS, highlight the newly identified probiotic strains that have demonstrated improvements in MetS, and elucidate their mechanisms of action, with the aim of offering contemporary perspectives for the future use of probiotics in mitigating MetS.

Ischemic stroke(IS) is the second leading cause of mortality and disability worldwide and neuroimmunity plays an important role in its occurrence and development. The pathogenesis of IS is associated with various metabolic disorders. Yet reports on the amelioration of neuroinflammation by modulating metabolic disorders in clinical practice are scarce. By screening drugs targeting the inflammatory cytokine pro IL-1β in the metabolism-related compound library, we first found that clofibrate, an antihyperlipidemic drug, has an anti-neuroinflammatory effect. However, the role of clofibrate in exerting anti-inflammatory effects in IS and its underlying mechanisms remain unclear. To further investigate the role of clofibrate, we administered clofibrate in an LPS-stimulated microglial cell model and in mice with transient middle cerebral artery occlusion. Notably, clofibrate lowered IL-1β expression, both in vivo and in vitro. Simultaneously, clofibrate reduced infarct volume after ischemia and reperfusion. Moreover, clofibrate affected IS by regulating the expression of NF-κB p65 and NLRP3, thus suppressing the expression of inflammatory factors. These findings suggest that clofibrate could be a prospective medication to alleviate neuroinflammation in IS.

Obesity and insulin resistance are well-established risk factors for atherosclerosis and cardiovascular disease (CVD). Although some obesity- and insulin resistance-related indices (OIRIs) have been linked to CVD, their associations with subclinical carotid atherosclerosis (SCA) in individuals with type 1 diabetes (T1D) remain unclear. This study aims to systematically explore and compare the associations of various common OIRIs with SCA in T1D population.

A total of 418 adult inpatients with classic T1D admitted from October 2008 to June 2021 to the First Affiliated Hospital of Air Force Medical University in Xi'an, China were included in this study. Demographic, anthropometric, and laboratory data were collected. Studied OIRIs comprised body mass index, waist-to-height ratio, waist-to-hip ratio (WHR), a body shape index, abdominal volume index, body adiposity index, body roundness index, conicity index, triglyceride-glucose index, visceral adiposity index, Chinese visceral adiposity index (CVAI), lipid accumulation product, estimated glucose disposal rate (eGDR), triglyceride-to-HDL ratio, and cardiometabolic index. Binary logistic regression, restricted cubic spline (RCS), and receiver operating characteristic curves were used to examine the associations of these indices with SCA.

In multivariable logistic regression analyses, after adjusting for potential confounders, per 1.0-standard deviation (SD) increase in CVAI (OR, 95% CI: 1.68, 1.16-2.47), eGDRWHR (eGDR calculated with WHR; OR, 95% CI: 0.44, 0.22-0.82), and eGDRWC (eGDR calculated with waist circumference; OR, 95% CI: 0.49, 0.24-0.93) were significantly associated with SCA. CVAI exhibited the highest area under the curve (AUC) in diagnosing SCA, with a value of 0.73 (95% CI: 0.69-0.77). RCS analyses indicated a linear and positive association between CVAI and SCA in the overall population and the females. Subgroup analyses and sensitivity analyses further supported the association between CVAI and SCA. Additionally, adding CVAI to the Steno Type 1 Risk Engine (ST1RE) improved the reclassification, but did not enhance the overall discriminative ability of ST1RE to identify SCA.

Among various OIRIs, CVAI shows the strongest association with SCA in adults with T1D. These findings suggest that CVAI may merit further longitudinal investigation as a potential marker for SCA assessment in this population.

The increase in sugar consumption has been associated with current metabolic disease epidemics. This study aimed to investigate the pancreatic molecular mechanisms involved in cellular stress, inflammation, mitogenesis, and apoptosis in metabolic disease induced by high-fructose diet. Here, we used biochemical, histopathological, Western blot, and immunohistochemistry methods to determine the metabolic and pancreatic alterations in male Wistar rats fed 20% fructose in drinking water for 15 weeks. High-fructose consumption in rats increased the immunopositivity and protein expression of glucose transporter 2 (GLUT2) and insulin in the pancreatic tissue, in association with abdominal adiposity, hyperglycemia, and hypertriglyceridemia. The expressions of cellular stress markers, glucose-regulated protein-78 (GRP78) and PTEN-induced putative kinase 1 (PINK1), were increased in the pancreas. The levels of interleukin (IL)-6, nuclear factor kappa B (NFκB), tumor necrosis factor α (TNFα), and IL-1β and components of the Nod-like receptor protein 3 (NLRP3) inflammasome were elevated. Excess fructose intake stimulated the activation of mitogenic extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK)1 as well as the apoptotic p53 and Fas pathways in the pancreas of rats. There was also an increase in caspase-8 and caspase-3 cleavage. Our findings revealed that dietary high-fructose in the pancreas causes hyperinsulinemia due to the upregulation of GLUT2 together with cellular stress and inflammatory markers, thereby stimulates mitogenic mitogen-activated protein kinase (MAPK) and apoptosis pathways, resulting in a complex pathological situation.

Little is known about the effect of bronchoscopic lung volume reduction using endobronchial valves (BLVR-EBV) on extrapulmonary manifestations like body composition, muscle function or metabolism. Pulmonary rehabilitation (PR) clearly addresses extrapulmonary manifestations of COPD, including physical inactivity and low muscle mass. However, the added impact of BLVR-EBV+PR remains unknown. Therefore, this study aimed to assess the effect of BLVR-EBV on body composition, muscle function and metabolic markers and whether PR has an additional impact on these outcomes.

Subjects with severe COPD eligible for both PR and BLVR-EBV were randomized into three groups: PR+BLVR-EBV, BLVR-EBV+PR, or only BLVR-EBV (n=97). Assessments included Dual Energy X-ray Absorptiometry, thigh muscle Computed Tomography, muscle strength measurements, accelerometry, and plasma (leptin, adiponectin, insulin, and triglycerides) at baseline and six months after the last intervention.

A total of 74 participants completed the study. At follow-up, there were significant increases in the groups combined and both groups separated in total weight, lean mass, fat mass, muscle strength, daily physical activity, and triglyceride levels while leptin/fat mass ratio levels were significantly reduced. No differences were found between groups who underwent BLVR-EVR alone or BLVR-EBV with PR.

BLVR-EBV results in significant increases in body weight, lean and fat mass, muscle strength and daily physical activity level, and impacts on adipokine profile, irrespective of PR. This underscores the systemic benefits of addressing lung hyperinflation in patients with severe COPD.

Diabetes-associated cognitive impairment (DACI) is a common complication of Type 2 diabetes mellitus (T2DM), with its mechanisms and treatments for DACI remaining incompletely clarified. This study investigated the protective efficacy of the novel lipid S-enantiomer of 9-palmitic acid esters of hydroxy stearic acids (S-9-PAHSA, S9P) in a high-fat diet-induced DACI mouse model.

Mice were randomly assigned to three groups: normal diet (ND), high-fat diet (HFD), and HFD + 30 mg/kg/day S9P (HFD + S9P). Fasting blood glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were conducted to assess blood glucose homeostasis. Morris Water Maze and Y maze tests evaluated cognitive function, and neuronal status was examined through pathological analysis, Golgi staining, and transmission electron microscopy (TEM). Colonic barrier integrity was assessed using periodic acid-Schiff and Alcian blue staining (AB-PAS) and immunohistochemistry (IHC) staining. Intestinal microbiota composition was analyzed by 16S rDNA sequencing, and serum metabolic characteristics were determined by metabolomics sequencing.

S9P improved glucose homeostasis and alleviated cognitive decline in DACI mice. It also mitigated neuronal damage, dendritic degeneration, and synaptic damage, while restoring colonic barrier integrity and ameliorating gut microbiome imbalances, insulin resistance, and lipid imbalance. Additionally, S9P regulated metabolite profiles and the PI3K/AKT/mTOR signaling pathways, and reduced astrocyte activation and neuroinflammatory responses in the hippocampus of HFD-induced DACI mice.

S9P had a protective effect against HFD-induced diabetic cognitive impairment closely related to the modulation of the gut-brain axis, suggesting that S9P has the potential to become a new therapeutic approach for DACI.

The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved with gut microbiota, while the underlying mechanism is unclear. Here, we investigated the role of inulin, a gut microbiota regulator, in the alleviation of PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism in both PCOS cohort and mice. Consistent with the cohort, inulin increased the abundance of microbial co-abundance group (CAG) 12 in PCOS mice, including Bifidobacterium species and other short-chain fatty acids (SCFAs)-producers. We further verified the enhancement of SCFAs biosynthesis capacity and fecal SCFAs content by inulin. Moreover, inulin decreased lipopolysaccharide-binding protein (LBP) and ameliorated ovarian inflammation in PCOS mice, whereas intraperitoneal lipopolysaccharide (LPS) administration reversed the protective effects of inulin. Furthermore, fecal microbiota transplantation (FMT) from inulin-treated patients with PCOS enhanced insulin sensitivity, improved lipid accumulation and thermogenesis, reduced hyperandrogenism and ovarian inflammatory response in antibiotic-treated mice. Collectively, these findings revealed that gut microbiota mediates the beneficial effects of inulin on metabolic disorder and ovarian dysfunction in PCOS. Therefore, modulating gut microbiota represents a promising therapeutic strategy for PCOS.