Upper tract urothelial carcinoma (UTUC) presents aggressive features and a tumor microenvironment with T cell depletion. However, the role of tumor-associated neutrophils in UTUC remains unclear. This study aimed to investigate how UTUC tumor-derived factors modulate neutrophils and their impact on T cell immune responses. Our findings demonstrate that UTUC secreted tumor-derived factors, with apolipoprotein A1 (Apo-A1) being the predominant factor, which upregulated arginase-1 expression in neutrophils. STAT3 activation was responsible for the upregulation of arginase-1 in neutrophils. Blocking the interactions between Apo-A1 and its receptors reduced arginase-1 expression in neutrophils treated with tumor tissue culture supernatant (TTCS). Moreover, both CD4+ T and CD8+ T cell proliferation were inhibited by neutrophils treated with Apo-A1 or TTCS. Importantly, blocking Apo-A1 signaling in neutrophils reversed the inhibitory effects on T cells. In UTUC patients, the neutrophil-to-lymphocyte ratio was higher than that in healthy subjects. The expression of arginase-1 in neutrophils and the level of Apo-A1 within UTUC tumors were negatively correlated with tumor-infiltrating CD4+ T cells. Additionally, neutrophils from UTUC patients showed increased expression of arginase-1 and exhibited inhibitory effects of T cell functions. These findings suggest that UTUC orchestrates an immune-suppressive microenvironment through Apo-A1-mediated upregulation of arginase-1 in neutrophils, ultimately leading to the inhibition of T cell proliferation.

Adipose tissue is an immunologically active organ that controls host physiology, partly through the release of mediators termed adipokines. In obesity, adipocytes and infiltrating leukocytes produce adipokines, which include the hormones adiponectin and leptin and cytokines such as tumour necrosis factor and IL-1β. These adipokines orchestrate immune responses that are collectively referred to as metabolic inflammation. Consequently, metabolic inflammation characterizes metabolic disorders and promotes distinct disease aspects, such as insulin resistance, metabolic dysfunction-associated liver disease and cardiovascular complications. In this unifying concept, adipokines participate in the immunological cross-talk that occurs between metabolically active organs in metabolic diseases, highlighting the fundamental role of adipokines in obesity and their potential for therapeutic intervention. Here, we summarize how adipokines shape metabolic inflammation in mice and humans, focusing on their contribution to metabolic disorders in the setting of obesity and discussing their value as therapeutic targets.

Obesity is a worldwide health problem with a rapidly rising incidence. In organ transplantation, increasing numbers of patients with obesity accumulate on waiting lists and undergo surgery. Obesity is in general conceptualized as a chronic inflammatory disease, potentially impacting alloimmune response and graft function. Here, we summarize our current understanding of cellular and molecular mechanisms that control obesity-associated adipose tissue inflammation and provide insights into mechanisms affecting transplant outcomes, emphasizing on the beneficial effects of weight loss on alloimmune responses.

Multiple myeloma (MM) is a complex hematological malignancy characterized by the clonal expansion of plasma cells in the bone marrow. Emerging studies have emphasized the importance of lipid metabolism, which is closely associated with the survival, proliferation, and drug resistance of tumor cells. The hypoxic environment in the bone marrow (BM) contributes to metabolic reprogramming in MM cells, including alterations in metabolite levels, changes in metabolic enzyme activity, and metabolic shifts. Cancer cells possess the ability to adapt their metabolism in order to fulfill their continuously increasing energy demands. In this review, we will discuss the alterations in lipid metabolism during the development of MM, and their reciprocal interactions with the tumor microenvironment.

Many scoring systems are used to evaluate malnutrition, but there is no consensus on which scoring system would be more appropriate. We aimed to investigate the effect of malnutrition in patients with non-valvular atrial fibrillation (NVAF) and to compare three scoring systems.

A total of 2592 patients with non-valvular AF from 35 different centers in Turkey were included in this prospective study. All participants were divided into two groups: 761 patients who died and 1831 patients who were alive. The malnutrition status of all participants was evaluated with three scoring systems. The primary outcome was all-cause mortality. The mean age of the population was 68.7 ± 11.1 years, and 55.5 % were female. According to Cox regression analysis, the geriatric nutritional risk index (GNRI) (HR = 0.989, 95 % CI: 0.982-0.997, p = 0.007), controlling nutritional status (CONUT) score (HR = 1.121, 95 % CI: 1.060-1.185, p < 0.001), and prognostic nutritional index (PNI) (HR = 0.980, 95 % CI: 0.962-0.999, p = 0.036) were found to be significant mortality predictors. ROC curve analysis indicated GNRI (AUC = 0.568), CONUT (AUC = 0.572), and PNI (AUC = 0.547) had moderate predictive values. Kaplan-Meier analysis showed that increasing the risk class based on GNRI (p < 0.001) and CONUT (p < 0.001) was associated with decreased survival, while PNI staging had no statistically significant effect (p = 0.266).

Malnutrition, determined by three scoring systems, was found to be an independent predictor of all-cause mortality in NVAF patients. Nutritional examination may provide useful information for prognosis and risk stratification in patients with NVAF.

Obesity can adversely impact respiratory function and limit physical activity (PA). Sleeve gastrectomy (SG) is an essential and uptrend treatment option for weight loss. However, the effect of SG on pulmonary function and PA in patients with obesity is still debated.

This is an observational study of 32 cases with obesity (BMI 43.86 ± 4.39) who underwent SG in a single center. Spirometry was performed before and 12 months after SG to investigate the pulmonary function of individuals. The main variables were forced expiratory volume (1s) (FEV1), Forced vital capacity (FVC), FEV1/FVC ratio, and maximum inspiratory pressure (MIP). The correlation of weight loss variables with findings was evaluated.

One year after surgery, patients lost an average of 23.42 kg (P <.001). The FEV1 and FVC were increased by 0.22 ml and 0.38 ml, respectively (p <.001). The absolute changes in FEV1 and FVS were significantly correlated with Total weight loss percentage (TWL). The 6-minute walking test (6MWT) results were significantly increased after surgery by 53.71 m (p <.001), and changes were correlated with TWL.

More than significant weight loss, the SG can also significantly improve the respiratory function and PA of individuals with obesity 12 months after surgery. Additionally, there was a positive correlation between weight loss and modification in lung function tests. The findings required studies with larger sample sizes and longer follow-up times to confirm and clarify.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disorder that primarily affects body folds and the genital area, with a higher prevalence in women across Europe. The pathogenesis of HS involves a complex interplay of intrinsic and extrinsic factors, including genetics, immunity, hormones, and environmental influences. HS is frequently associated with a variety of comorbidities, such as metabolic, endocrine, and gastrointestinal conditions, as well as mental health disorders. Although the symptoms of HS are generally similar in both men and women, female patients may experience exacerbations of HS due to hormonal fluctuations during menstruation, pregnancy, breastfeeding, and menopause. These hormonal changes require special consideration by clinicians when managing HS in women. Due to its chronic nature and frequent flare-ups, HS significantly impacts patients' quality of life, affecting social interactions, emotional well-being, and psychological health. Women with HS may also experience sexual dysfunction, which is further exacerbated by emotional burdens such as shame, loss of femininity, and diminished intimacy. This review highlights key aspects of HS, extending beyond its skin manifestations to address endocrine, psychological, and nutritional aspects in the female population. It also underscores the importance of multidisciplinary collaboration in providing comprehensive care for women with this debilitating condition. Given the limited and largely off-label treatment options, a holistic approach is essential to ensure an appropriate management.

Uveitis refers to a diverse group of inflammatory diseases that affecting the uveal tract, comprising the iris, ciliary body, and choroid, with potential repercussions ranging from visual impairment to blindness. The role of autoimmunity in uveitis etiology is complex and still under investigation. CD4+ T cells intricately regulate immune responses in uveitis through their diverse subtypes: Th1, Th2, Th17, Treg (T regulatory), and Tfh (follicular T helper) cells. Each T cell subtype secretes specific cytokines with either pathogenic or protective implications in uveitis. Th1 cells, characterized by IFN-γ secretion and T-bet expression, drive type 1 immune responses against intracellular pathogens. Conversely, Th2 cells, which produce interleukin (IL)-4, IL-5, and IL-13 and express the transcription factor GATA3, mediate type 2 immune responses to larger extracellular threats like helminths. Th17 cells, generating IL-17 and IL-22 and controlled by RORγt, engage in type 3 immune responses against select pathogens. Tfh cells, releasing IL-21 and governed by Bcl6, aid B cell antibody production. Conversely, Tregs, identified by Foxp3, exert regulatory functions in immune homeostasis. This review delves into the roles of CD4+ T cell-derived cytokines in uveitis, emphasizing their intricate involvement in disease progression and resolution. Insight into these mechanisms might guide therapeutic approaches targeting CD4+ T cell responses in uveitis management.

Recent data showed an association between malnutrition and increased all-cause mortality and thromboembolic risk in patients with atrial fibrillation (AF). However, the impact of malnutrition on the clinical outcomes for patients undergoing catheter ablation for AF is still debated. Our study aimed to examine this relationship using all existing available data.

We conducted a systematic review of MEDLINE and EMBASE databases from inception to April 2024, analyzing the association between malnutrition, assessed by the Geriatric Nutritional Risk Index (GNRI), and the risk of AF recurrence in patients who underwent catheter ablation for AF, compared to those without malnutrition. Relative Risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method.

We included 3 cohort studies with 1697 participants undergoing AF ablation (10.9%) who had malnutrition indicated by GNRI score below 98. Patients with malnutrition had a higher risk of AF recurrence following catheter ablation for AF compared to those without malnutrition (Pooled RR = 2.74, 95% CI 1.36-5.51, I 2 = 67%, p = .005).

Our pooled analysis indicates that malnourished patients undergoing catheter ablation for AF have an increased risk of AF recurrence compared to non-malnourished patients.

Adiponectin is a potent uterine tocolytic that decreases with gestational age, suggesting it could be a maternal metabolic quiescence factor. Maternal stress can influence preterm birth risk, and adiponectin levels may be stress responsive.

We characterized associations between adiponectin and glucocorticoids with preterm birth and modeled their predictive utility. We hypothesized maternal plasma adiponectin and cortisol are inversely related and lower adiponectin and higher cortisol associate with preterm birth.

We performed a nested case-control study using biobanked fasting maternal plasma. We included low-risk singleton pregnancies, and matched 1:3 (16 preterm, 46 term). We quantified high molecular weight (HMW), low molecular weight (LMW), and total adiponectin using an enzyme-linked immunosorbent assay. We validated a high-performance liquid chromatography-tandem mass spectrometry serum assay for use in plasma, to simultaneously measure cortisol, cortisone, and 5 related steroid hormones. We used linear/logistic regression to compare group means and machine learning for predictive modeling.

The preterm group had lower mean LMW adiponectin (3.07 μg/mL vs 3.81 μg/mL at 15 weeks (w) 0 days (d), P = .045) and higher mean cortisone (34.4 ng/mL vs 29.0 ng/mL at 15w0d, P = .031). The preterm group had lower cortisol to cortisone and lower LMW adiponectin to cortisol ratios. We found HMW adiponectin, cortisol to cortisone ratio, cortisone, maternal height, age, and prepregnancy body mass index most strongly predicted preterm birth (area under the receiver operator curve = 0.8167). In secondary analyses, we assessed biomarker associations with maternal self-reported psychosocial stress. Lower perceived stress was associated with a steeper change in cortisone in the term group.

Overall, metabolic and stress biomarkers are associated with preterm birth in this healthy cohort. We identify a possible mechanistic link between maternal stress and metabolism for pregnancy maintenance.

Periodontitis is a frequent local inflammatory disease. The microbiota and repeated exposure to bacterial endotoxins triggers excessive inflammation through oral mucosal immunity and sometimes leads to a destructive effect on the supportive mucosal tissues around the teeth. Elimination of the pathogens and increasing the tolerance of the cellular immune response is crucial in addition to standard dental therapies like mechanical debridement. Based on our experience with immune-mediated diseases, especially primary immunodeficiency diseases, we wrote this review to discuss the treatment alternatives for severe periodontal disease. Risk factors are malnutrition, vitamin deficiencies, smoking, systemic inherited and acquired immune-mediated diseases, infections, endocrinological diseases, and pharmacological agents that may accompany periodontitis. The diagnosis and treatment of dietary deficiencies, as well as the addition of nutritional supplements, may aid in epithelial regeneration and immune system function. Recently, modifications to the therapeutic option for severe periodontitis have been made depending on the fact that the immune response against bacteria may modify the severity of periodontal inflammation. The anti-inflammatory therapies support or inhibit the host's immune response. The clinical approach to severe periodontitis should extend beyond classical therapies. There is a need for a diverse therapeutic strategy that supports the epithelial barrier, which is the crucial component of innate immunity against microbiota. Leukocytes are the main cellular component in periodontal inflammation. Anti-inflammatory therapeutic options directed at leukocytes, such as IL-17 and IL-23-targeted therapies, could be the candidates for the treatment of severe periodontitis. Therapy against other inflammatory cytokines, IL-1, IL-6, IL-12, IL-23, TNF-alpha, PGE2, and cytokine receptors, could also be used in periodontal inflammation control.

In addition to conventional treatments, there is growing interest in preventive and complementary therapies. Proper nutrition can prevent the manifestation of several chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer, and can attenuate the severity of these diseases. Edible mushrooms have been used as nutrition and medicine for thousands of years. The spectrum and quantity of their medicinal compounds made them a widely investigated target both in basic research and clinical trials. The most abundant and medically important components are polysaccharides, terpenoids, phenols, and heterocyclic amines, but bioactive proteins, vitamins, including vitamin D, polyunsaturated fatty acids, and essential minerals are also important ingredients with noteworthy health benefits. Mushroom extracts have anti-diabetic, anti-hyperlipidemic, anti-inflammatory, antioxidant, cardioprotective, anti-osteoporotic, and anti-tumor effects and are well tolerated, even by cancer patients. In our previous review we detailed the molecular aspects of the development of type 2 diabetes, discussing the role of physical activity and diet, but we did not detail the role of medicinal mushrooms as part of nutrition. In this review, we aimed to summarize the most important medical mushrooms, along with their natural habitats, growing conditions, and components, that are presumably sufficient for the prevention and treatment of insulin resistance.

Obesity, the fifth leading cause of death globally and linked to chronic low-grade inflammation and development of numerous severe pathologies, is a major public health problem. Fermented foods, probiotics, and postbiotics emerge as promising avenues for combating obesity and inflammation. The aim of our study was to develop and characterize phyto-postbiotics corresponding to prebiotic compounds fermented by gut bacteria, which could act on obesity and related-inflammation. Chicory extract fermented by Akkermansia muciniphila (C-Akm) was selected as the most antioxidant of 20 fermented extracts. The identification of metabolites derived from C-Akm extract has enabled us to detect mostly amino acids, acids, and some polyphenols (daidzein and genistein). The anti-inflammatory and anti-obesity activities of C-Akm extract were studied by testing the extract (50 μg/mL) on the polarization of THP-1 into macrophages, the secretion of pro-inflammatory cytokines in LPS-stimulated PBMCs, and the secretion of leptin and adiponectin in adipospheroids derived from human adipose stem cells. Finally, the extract was examined in 3D co-culture model mimicking inflamed obese adipose tissue. We found that C-Akm extract decreased ROS generation, TNF-α and Il-6 gene expression in polarized macrophages, INFγ and IL-17A secretion in LPS-stimulated PBMCs stimulated with LPS. It also decreased leptin expression while increasing adiponectin and HSL expression levels in both adipocytes and co-cultures. In addition, C-Akm extract stimulated adiponectin secretion in the co-culture model. Finally, our in vitro investigations demonstrated the potential benefits of C-Akm extract in the prevention and treatment of obesity-related inflammation.

Cardiovascular diseases (CVDs), including heart failure, pose a significant economic and health burden worldwide. Current treatment strategies for heart failure are greatly limited, in that they mainly mitigate symptoms or delay further progression. In contrast, therapies aimed at proactively preventing the onset of heart failure could greatly improve outcomes. Adiponectin is an adipocyte-derived hormone that confers an array of cardioprotective effects. It exerts anti-inflammatory effects, improves metabolic function, mitigates endothelial cell dysfunction, and reduce cardiomyocyte cell death. Furthermore, it has gained increasing attention for its ability to activate autophagy, a conserved cellular pathway that facilitates the degradation and recycling of cell components. The disruption of autophagy has been linked to CVDs including heart failure. Additionally, growing evidence also points to specific forms of autophagy, namely mitophagy and lipophagy, as crucial adaptive responses in protection against CVDs. The protective effects of adiponectin, autophagy, mitophagy, and lipophagy against CVDs along with potential therapeutic implications will be discussed.

Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.

Hepatic fibrosis, a degenerative liver lesion, significantly contributes to the deterioration and mortality among patients with chronic liver diseases. The condition arises from various factors including toxins, such as alcohol, infections like different types of viral hepatitis, and metabolic diseases. Currently, there are no effective treatments available for liver fibrosis. Recent research has shown that adiponectin (ADPN) exhibits inhibitory effects on hepatic fibrosis. ADPN, an adipocytokine secreted by mature adipocytes, features receptors that are widely distributed across multiple tissues, especially the liver. In the liver, direct effects of ADPN on liver fibrosis include reducing inflammation and regulating hepatic stellate cell proliferation and migration. And its indirect effects include alleviating hepatic endoplasmic reticulum stress and reducing inflammation in hepatic lobules, thereby mitigating hepatic fibrosis. This review aims to elucidate the regulatory role of ADPN in liver fibrosis, explore how ADPN and its receptors alleviate endoplasmic reticulum stress, summarize ADPN detection methods, and discuss its potential as a novel marker and therapeutic agent in combating hepatic fibrosis.

Rationale Obesity is an independent risk factor for the occurrence and development of tumors. Obesity is influenced by signaling of adipokines, which are secreted factors from adipocytes and resident immune cells within adipose tissues that mediate lipid metabolism. More recently, adipokines have been implicated in chronic inflammation as well as in tumor formation and growth. Among them, resistin has received increasing attention in research related to the growth and expansion of solid tumors and hematological cancers through various signaling pathways. Objective and findings We reviewed the physiological, biochemical, and immune functions of adipose tissue, with a focus on the structure and expression of resistin and adipokines within multiple adipose cell types, their signaling pathways and putative effects on tumor cells, as well as their in vivo regulation. Current evidence indicates that adipokines such as resistin act as pro-inflammatory factors to stimulate immune cells which, in turn, promotes tumor angiogenesis, connective tissue proliferation, and matrix fibrosis. Concurrently, in states of metabolic dysfunction and lipotoxicity in obese individuals, the numbers and functions of immune cells are compromised, leading to an immunosuppressive environment that fosters tumor cell survival and weak cancer immune monitoring. Conclusion Adipokines such as resistin are important to the development of obesity-related tumors. Clarifying the roles for obesity-related factors in immune regulation and tumor progression may lead to the discovery of novel anti-tumor strategies for targeting obesity factors such as resistin to limit tumor growth and manage obesity, or both.

Menopause represents a pivotal physiological transition characterized by hormonal fluctuations and an augmented susceptibility to chronic diseases. The relationship between menopause and heightened disease risk may be attributed in part to alterations in low-grade chronic inflammation and adiposity.

Three databases were searched for studies assessing differences in inflammation and body adiposity between pre- and postmenopausal women. Meta-analysis examined the association between menopausal status and key inflammatory biomarkers, including leptin, adiponectin, interleukin-6, tumour necrosis factor-α and c-reactive protein, and indices of body adiposity (fat mass, waist circumference, waist-to-hip-ratio and body mass index). The National Institute of Health Quality Assessment Tool for Observational and Cross-sectional studies was used to evaluate quality of studies, and GRADE-assessed evidence certainty.

Levels of adiponectin and leptin were higher in postmenopausal women than in premenopausal women [(1.30 μg/ml, 95 % CI; 0.56 to 2.03 μg/ml, p = 0.001), (0.88 ng/ml; 95 % CI: 0.22 to 1.52; p = 0.008)]. A trend towards significance was observed for tumour necrosis factor-α (0.59 pg/ml, 95 % CI; -0.07 to 1.26 pg/ml, p = 0.080), with no significant differences in interleukin-6 and c-reactive protein [(0.83 pg/ml, 95 % CI; -0.24 to 1.91 pg/ml, p = 0.128), (0.06 mg/ml, 95 % CI; -0.17 to 0.29, p = 0.606)]. Postmenopausal women had greater waist circumference, waist-to-hip-ratio and body mass index than premenopausal women [(0.74 cm; 95 % CI: 1.02 to 0.47; p ≤0.001), (0.78; 95 % CI: 1.47 to -0.09; p = 0.027), (0.31 kg/m2; 95 % CI: 0.50 to 0.12; p = 0.001)].

Postmenopausal women had higher adipokine levels and greater adiposity. However, given the low certainty of the available evidence, future prospective cohort studies assessing inflammatory changes over the menopausal transition are warranted to inform future clinical decisions. Protocol registered on the Open Science Framework (OSF-ID: 10.17605/OSF.IO/DY8T6).

Adipose tissue engraftment has become a promising strategy in the field of regenerative surgery; however, there are notable challenges associated with it, such as resorption of 50‑90% of the transplanted fat or cyst formation due to fat necrosis after fat transplantation. Therefore, identifying novel materials or methods to improve the engraftment efficiency is crucial. The present study investigated the effects of nervonic acid (NA), a monounsaturated very long‑chain fatty acid, on adipogenesis and fat transplantation, as well as its underlying mechanisms. To assess this, NA was used to treat cells during adipogenesis in vitro, and the expression levels of markers, including PPARγ and CEBPα, and signaling molecules were detected through reverse transcription‑quantitative PCR and western blotting. In addition, NA was mixed with fat grafts in in vivo fat transplantation, followed by analysis through Oil Red O staining, hematoxylin & eosin staining and immunohistochemistry. It was demonstrated that NA treatment accelerated adipogenesis through activation of the Akt/mTOR pathway and inhibition of Wnt signaling. NA treatment enriched the expression of Akt/mTOR signaling‑related genes, and increased the expression of genes involved in angiogenesis and fat differentiation in human mesenchymal stem cells (MSCs). Additionally, NA effectively improved the outcome of adipose tissue engraftment in mice. Treatment of grafts with NA at transplantation reduced the resorption of transplanted fat and increased the proportion of perilipin‑1+ adipocytes with a lower portion of vacuoles in mice. Moreover, the NA‑treated group exhibited a reduced pro‑inflammatory response and had more CD31+ vessel structures, which were relatively evenly distributed among viable adipocytes, facilitating successful engraftment. In conclusion, the present study demonstrated that NA may not only stimulate adipogenesis by regulating signaling pathways in human MSCs, but could improve the outcome of fat transplantation by reducing inflammation and stimulating angiogenesis. It was thus hypothesized that NA could serve as an adjuvant strategy to enhance fat engraftment in regenerative surgery.

Obesity is a prevalent metabolic disease that reduces bacterial diversity, colonizes the epidermis with lipophilic bacteria, and increases intestinal pro-inflammatory species, all of which lead to impaired epithelial barriers. Adipose tissue secretes immunomodulatory molecules, such as adipokines, leptin, and adiponectin, which alters the morphology of adipocytes and macrophages as well as modulates T cell differentiation and peripheral Th2-dominated immune responses. Atopic dermatitis (AD) and obesity have similar pathological manifestations, including inflammation as well as insulin and leptin resistance. This review examines the major mechanisms between obesity and AD, which focus on the effect on skin and gut microbiota, immune responses mediated by the toll like receptor (TLR) signaling pathway, and changes in cytokine levels (TNF-a, IL-6, IL-4, and IL13). Moreover, we describe the potential effects of adipokines on AD and finally mechanisms by which PPAR-γ suppresses and regulates type 2 immunity.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 μM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

Adipokines play essential roles in regulating a range of biological processes, but growing evidence indicates that they are also fundamental in immunological mechanisms and, primarily, inflammatory responses. Adipokines mediate their actions through specific receptors. However, although adipokine receptors are widely distributed in many cell and tissue types, limited data are available on their expression in mast cells (MCs) and, consequently, adipokine's significance in the modulation of MC activity within the tissues. In this study, we demonstrate that rat peritoneal MCs constitutively express the leptin receptor (i.e. LEPR), adiponectin receptors (i.e. ADIPOR1 and ADIPOR2) and the chemerin receptor (i.e. CMKLR1). We also found that LEPR, ADIPOR1, ADIPOR2 and CMKLR1 expression in MCs changes in response to stimulation by their specific ligands and some cytokines with potent proinflammatory properties. Furthermore, the involvement of intracellular signaling molecules in leptin-, adiponectin- and chemerin-induced MC response was analyzed. Overall, our findings suggest that adipokines leptin, adiponectin and chemerin can significantly affect the activity of MCs in various processes, especially during inflammation. These observations may contribute significantly to understanding the relationship between adipokines, immune mechanisms and diseases or conditions with an inflammatory component.

Identifying anti-inflammatory peptides (AIPs) and antimicrobial peptides (AMPs) is crucial for the discovery of innovative and effective peptide-based therapies targeting inflammation and microbial infections. However, accurate identification of AIPs and AMPs remains a computational challenge mainly due to limited utilization of peptide sequence information. Here, we propose PepNet, an interpretable neural network for predicting both AIPs and AMPs by applying a pre-trained protein language model to fully utilize the peptide sequence information. It first captures the information of residue arrangements and physicochemical properties using a residual dilated convolution block, and then seizes the function-related diverse information by introducing a residual Transformer block to characterize the residue representations generated by a pre-trained protein language model. After training and testing, PepNet demonstrates great superiority over other leading AIP and AMP predictors and shows strong interpretability of its learned peptide representations. A user-friendly web server for PepNet is freely available at http://liulab.top/PepNet/server .

Ischemia/reperfusion injury (IRI) is a key determining agent in the pathophysiology of clinical organ dysfunction. It is characterized by an aseptic local inflammatory reaction due to a decrease in blood supply, hence deprivation of dependent oxygen and nutrients. In instances of liver transplantation, this injury may have irreversible implications, resulting in eventual organ rejection. The deterioration associated with IRI is affected by the hepatic health status and various factors such as alterations in metabolism, oxidative stress, and pro-inflammatory cytokines. The primary cause of inflammation is the initial immune response of pro-inflammatory cytokines, while Kupffer cells (KFCs) and neutrophil-produced chemokines also play a significant role. Upon reperfusion, the activation of inflammatory responses can elicit further cellular damage and organ dysfunction. This review discusses the interplay between chemokines, pro-inflammatory cytokines, and other inflammatory mediators that contribute to the damage to hepatocytes and liver failure in rats following IR. Furthermore, it delves into the impact of anti-inflammatory therapies in safeguarding against liver failure and hepatocellular damage in rats following IR. This review investigates the correlation between cytokine factors and liver dysfunction via examining databases, such as PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate.

Cellulitis is a bacterial skin infection that tends to recur. Previous studies have identified several risk factors that may contribute to its pathogenesis. Obesity is an increasingly prevalent worldwide disease that has been associated with skin and soft tissue infections.

The aim of our systematic review and meta-analysis was to investigate the association of cellulitis with obesity.

The Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for the relevant studies from the inception of each respective database to March 13, 2021. Case-control, cross-sectional, or cohort studies that examined the odds or risk of increased BMI in patients with cellulitis were included. This study was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Newcastle-Ottawa scale (NOS) was used to evaluate the risk of bias in included studies.

In total, 9 case-control studies were included in our quantitative meta-analysis with a total of 68,148 study participants. A significant association was found between cellulitis and obesity (pooled odds ratio [OR] 2.67, 95% CI 1.91-3.71). No significant association was observed between cellulitis and being overweight (pooled OR 1.69, 95% CI 0.99-2.88). Patients with cellulitis were also found to have 1.63-fold increased odds of being male (pooled OR 1.63, 95% CI 1.12-2.38).

Our findings suggest that cellulitis is significantly associated with obesity. Maintaining a healthy BMI may be indicated for patients presenting with cellulitis.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms and to determine if current data supports their future progression to clinical trials.

The incidence of obesity and asthma continues to enhance, significantly impacting global public health. Adipose tissue is an organ that secretes hormones and cytokines, causes meta-inflammation, and contributes to the intensification of bronchial hyperreactivity, oxidative stress, and consequently affects the different phenotypes of asthma in obese people. As body weight increases, the risk of severe asthma increases, as well as more frequent exacerbations requiring the use of glucocorticoids and hospitalization, which consequently leads to a deterioration of the quality of life. This review discusses the relationship between obesity and severe asthma, the underlying molecular mechanisms, changes in respiratory function tests in obese people, its impact on the occurrence of comorbidities, and consequently, a different response to conventional asthma treatment. The article also reviews research on possible future therapies for severe asthma. The manuscript is a narrative review of clinical trials in severe asthma and comorbid obesity. The articles were found in the PubMed database using the keywords asthma and obesity. Studies on severe asthma were then selected for inclusion in the article. The sections: 'The classification connected with asthma and obesity', 'Obesity-related changes in pulmonary functional tests', and 'Obesity and inflammation', include studies on subjects without asthma or non-severe asthma, which, according to the authors, familiarize the reader with the pathophysiology of obesity-related asthma.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses. More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD. The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications.

Adiponectin is one of the most important adipokines in human beings. Obesity and sarcopenia are associated with a low-level chronic inflammatory status, and adiponectin plays an anti-inflammatory role.

The objective of the current work was to study the association between muscle mass, determined via bioelectrical impedance (BIA), and circulating adiponectin levels among obese patients with metabolic syndrome who are older than 60 years of age.

We performed a cross-sectional study incorporating 651 patients with obesity and metabolic syndrome. Anthropometric data, BIA data (total fat mass (FM), fat-free mass (FFM), fat-free mass index (FFMi), skeletal muscle mass (SMM) and skeletal muscle mass index (SMMi)), arterial pressure, HOMA-IR (homeostasis model assessment of insulin resistance), and biochemical parameters were recorded.

The patients were separated into two groups based on their median SMMi (skeletal muscle mass index) levels. The low-SMMi group presented adiponectin levels that were higher than those in the high-SMMi group (delta value: 4.8 + 0.7 ng/dl: p = 0.02). Serum adiponectin values were negatively correlated with fat mass (FM), fat-free mass (FFM), fat-free mass index (FFMi), SMM, and SMMi. Adiponectin presented a negative correlation with HOMA-IR and a positive correlation with HDL-cholesterol. In the final multivariate model using SMMi as a dependent variable, adiponectin levels explained 18 % of the variability (Beta -0.49, CI95% -0.89 to -0.16) after adjusting for age and gender.

Serum adiponectin levels are negatively associated with low skeletal muscle mass among obese subjects with metabolic syndrome who are older than 60 years of age.

White adipose tissue secretes a number of peptide hormones. The aim of this paper was to determine the role of leptin, adiponectin and interleukin-10 and interleukin-6 on the development of graft rejection in protocol biopsy after kidney transplantation.

In a prospective analysis (n = 104), we monitored the values of leptin, adiponectin, IL-6, and IL-10 prior to the transplantation and in the 3rd month after the transplantation. The protocol biopsy of the graft was performed in the 3rd month after the transplantation. The group was divided into the following according to the biopsy result: negative result, IFTA 1, borderline, and DSA positive.

After adjusting for the differences in the baseline recipient and donor characteristics, we identified the hyperleptinaemia baseline (HR = 2.0444, P = 0.0341) and month 3 (HR = 49.8043, P < 0.0001) as independent risk factors for borderline changes in the protocol biopsy. The hyperleptinaemia baseline (HR = 7.4979, P = 0.0071) and month 3 (HR = 9.7432, P = 0.0057) are independent risk factors for de novo DSA positivity. A low value of IL-10 month 3 is a risk factor for de novo DSA positivity (HR = 3.0746, P = 0.0388).

Higher leptin levels and low values of IL-10 might play a role in rejection and de novo DSA production.

The co-occurrence of asthma and obesity is becoming an increasingly common health problem. It became clear that both diseases are closely related, since overweight/obesity are associated with an increased risk of asthma development, and more than half of the subjects with severe or difficult-to-treat asthma are obese. Currently, there are no specific guidelines for the treatment of this group of patients. The mechanisms involved in the asthma-obesity phenotype include low-grade chronic inflammation and changes in pulmonary physiology. However, genetic predispositions, gender differences, comorbid conditions, and gut microbiota also seem to be important. Regulatory peptides affect many processes related to the functioning of the respiratory tract and adipose tissue. Adipokines such as leptin, adiponectin, resistin, and the less studied omentin, chemerin, and visfatin, as well as the gastrointestinal hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and neuropeptides, including substance P or neuropeptide Y, can play a significant role in asthma with obesity. The aim of this article is to provide a concise review of the contribution of particular peptides in inflammatory reactions, obesity, asthma, and a combination of both diseases, as well as emphasize their potential role in the effective treatment of the asthma-obesity phenotype in the future.

Periodontitis is a chronic inflammatory disease caused by plaque biofilm which shares risk factors with systemic chronic diseases such as diabetes, cardiovascular disease, and osteoporosis. Many studies have found increased prevalence and rate of progression of periodontal disease in children with common metabolic disorders. Although the causal relationship and specific mechanism between them has not been determined yet. The aim of this paper is to progress on the impact of metabolic disorders on periodontal health in children and the underlying mechanisms, which provides new evidences for the prevention and intervention of metabolic disorders and periodontitis in children.

Tuberculosis patients with diabetes, have higher sputum bacillary load, delayed sputum conversion, higher rates of drug resistance, higher lung cavitary involvement and extra-pulmonary TB infection, which is called as "Diabetes-Tuberculosis Nexus". However, recently we have shown a reciprocal relationship between latent tuberculosis infection and insulin resistance, which has not been reported before. In this review, we would first discuss about the immune-endocrine network, which operates during pre-diabetes and incipient diabetes and how it confers protection against LTBI. The ability of IR to augment anti-TB immunity and the immunomodulatory effect of LTBI to quench IR were discussed, under IR-LTB antagonism. The ability of diabetes to impair anti-TB immunity and ability of active TB to worsen glycemic control, were discussed under "Diabetes-Tuberculosis Synergy". The concept of "Fighter Genes" and how they confer protection against TB but susceptibility to IR was elaborated. Finally, we conclude with an evolutionary perspective about how IR and LTBI co-evolved in endemic zones, and have explained the molecular basis of "IR-LTB" Antagonism" and "DM-TB Synergy", from an evolutionary perspective.

Severe acute pancreatitis (SAP) is a dangerous condition with a high mortality rate. Many studies have found an association between adipokines and the development of SAP, but the results are controversial. Therefore, we performed a meta-analysis of the association of inflammatory adipokines with SAP.

We screened PubMed, EMBASE, Web of Science and Cochrane Library for articles on adipokines and SAP published before July 20, 2023. The quality of the literature was assessed using QUADAS criteria. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to assess the combined effect. Subgroup analysis, sensitivity analysis and publication bias tests were also performed on the information obtained.

Fifteen eligible studies included 1332 patients with acute pancreatitis (AP). Pooled analysis showed that patients with SAP had significantly higher serum levels of resistin (SMD = 0.78, 95% CI:0.37 to 1.19, z = 3.75, P = 0.000). The difference in leptin and adiponectin levels between SAP and mild acute pancreatitis (MAP) patients were not significant (SMD = 0.30, 95% CI: -0.08 to 0.68, z = 1.53, P = 0.127 and SMD = 0.11, 95% CI: -0.17 to 0.40, z = 0.80, P = 0.425, respectively). In patients with SAP, visfatin levels were not significantly different from that in patients with MAP (SMD = 1.20, 95% CI: -0.48 to 2.88, z = 1.40, P = 0.162).

Elevated levels of resistin are associated with the development of SAP. Resistin may serve as biomarker for SAP and has promise as therapeutic target.

This review provides an overview of the key role played by perivascular adipose tissue (PVAT) in the protection of cardiovascular health. PVAT is a specific type of adipose tissue that wraps around blood vessels and has recently emerged as a critical factor for maintenance of vascular health. Through a profound exploration of existing research, this review sheds light on the intricate structural composition and cellular origins of PVAT, with a particular emphasis on combining its regulatory functions for vascular tone, inflammation, oxidative stress, and endothelial function. The review then delves into the intricate mechanisms by which PVAT exerts its protective effects, including the secretion of diverse adipokines and manipulation of the renin-angiotensin complex. The review further examines the alterations in PVAT function and phenotype observed in several cardiovascular diseases, including atherosclerosis, hypertension, and heart failure. Recognizing the complex interactions of PVAT with the cardiovascular system is critical for pursuing breakthrough therapeutic strategies that can target cardiovascular disease. Therefore, this review aims to augment present understanding of the protective role of PVAT in cardiovascular health, with a special emphasis on elucidating potential mechanisms and paving the way for future research directions in this evolving field.

We aimed to evaluate the association between the adipokines: Leptin, Adiponectin, Resistin, and high sensitive-C-reactive protein (hs-CRP) with clinical, radiographical and magnetic resonance imaging (MRI) assessment of knee osteoarthritis (OA) severity.

We performed a cross-sectional study in participants with earlier knee OA. Demographics, clinical (WOMAC), radiographical and MRI (BLOKS scoring) severity of knee OA were assessed. Serum leptin, adiponectin, resistin and hs-CRP were measured. Association of adipokines and hs-CRP with clinical, radiographic and MRI severity outcomes were evaluated using regression models with adjustment with age, sex, and body mass index (BMI).

137 participants with earlier knee OA (82% women, mean ​± ​SD age: 55.5 ​± ​7.8 years) were included. Participants had moderate knee OA symptoms, mean WOMAC pain and function were 30.6 ​± ​18.0, and 31.7 ​± ​19.8 respectively. Mean BMI was 27.0 ​± ​5.9 ​kg/m2. After adjustment with age, sex and BMI, serum leptin was positively associated with osteophyte size, cartilage integrity, infrapatellar synovitis and effusion. While hs-CRP was associated with meniscus extrusion and adiponectin was associated with WOMAC pain and function.

Serum adipokines, particularly leptin was associated with severity of various structural defects of the knee joint on MRI beyond age, sex and BMI in earlier knee OA.

Obesity, a complex and multifactorial disease influenced by genetic, environmental, and psychological factors, has reached epidemic proportions globally, posing a significant health challenge. In addition to its established association with cardiovascular disease and type II diabetes, obesity has been implicated as a risk factor for various cancers. However, the precise biological mechanisms linking obesity and cancer remain largely understood. Adipose tissue, an active endocrine organ, produces numerous hormones and bioactive molecules known as adipokines, which play a crucial role in metabolism, immune responses, and systemic inflammation. Notably, adiponectin (APN), the principal adipocyte secretory protein, exhibits reduced expression levels in obesity. In this scoping review, we explore and discuss the role of APN in influencing cancer in common malignancies, including lung, breast, colorectal, prostate, gastric, and endometrial cancers. Our review aims to emphasize the critical significance of investigating this field, as it holds great potential for the development of innovative treatment strategies that specifically target obesity-related malignancies. Furthermore, the implementation of more rigorous and comprehensive prevention and treatment policies for obesity is imperative in order to effectively mitigate the risk of associated diseases, such as cancer.

The World Health Organization (WHO) reported that the prevalence of obesity in the Kingdom of Saudi Arabia (KSA) is 33.7% (women 39.5% and men 29.5%), respectively. The effects of obesity on airway inflammation and respiratory mechanics as well as the function of adipose tissue has a key role in the development of various lung diseases. Therefore, this study aimed to compare the level of cytokines between obese (BMI ≥ 30) and non-obese participants and to assess their association with BMI, airways inflammation and pulmonary function.

One-hundred and seven non-smoking students (18-25 years of age) were recruited using convenience sampling technique for comparative cross-sectional study. Of them, 80 students were eligible and included in the analysis; 54 were non-obese (BMI<30) and 26 were obese (BMI ≥ 30). All the participants underwent anthropometric measurements, fractional exhaled nitric oxide (FeNO) measurement, spirometry and cytokines measurement (IL-6, IL-1β, GM-CSF, IL-7, IL-8 and IL-10). Measurements were compared between obese and non-obese groups. Then a correlation test was made between pro- and anti-inflammatory cytokines with BMI, pulmonary function test finding and FeNO.

The prevalence of obesity was 32.5% in the study population. Levels of pro-inflammatory cytokine IL-6 levels was significantly higher in obese than non-obese participants (p = 0.044). The level of FeNO log was significantly higher in obese participants than non-obese (p = 0.002). The pro-inflammatory cytokine IL-6 showed positive correlation with BMI while GMCSF showed negative correlation with FVC (p<0.05).

The levels of pro-inflammatory cytokine IL-6 was found to be significantly higher in obese participants than non-obese participants. Furthermore, it showed positive correlation with BMI whereas pro-inflammatory cytokine GMCSF showed negative correlation with FVC.

While immune checkpoint inhibitors show success in treating a subset of patients with certain late-stage cancers, these treatments fail in many other patients as a result of mechanisms that have yet to be fully characterized. The process of CD8 T cell exhaustion, by which T cells become dysfunctional in response to prolonged antigen exposure, has been implicated in immunotherapy resistance. Single-cell RNA sequencing (scRNA-seq) produces an abundance of data to analyze this process; however, due to the complexity of the process, contributions of other cell types to a process within a single cell type cannot be simply inferred. We constructed an analysis framework to first rank human skin tumor samples by degree of exhaustion in tumor-infiltrating CD8 T cells and then identify immune cell type-specific gene-regulatory network patterns significantly associated with T cell exhaustion. Using this framework, we further analyzed scRNA-seq data from human tumor and chronic viral infection samples to compare the T cell exhaustion process between these two contexts. In doing so, we identified transcription factor activity in the macrophages of both tissue types associated with this process. Our framework can be applied beyond the tumor immune microenvironment to any system involving cell-cell communication, facilitating insights into key biological processes that underpin the effective treatment of cancer and other complicated diseases.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Here, we fabricated a hybrid nanoparticle composed of polydopamine nanoparticles (pNPs), alendronate (Al) and genipin (GP) for cranial bone defect repair. Al was crosslinked into pNPs via GP (Al@pNPs), after which hybrid nanoparticles were obtained. By embedding these Al@pNPs into the fibrin hydrogels, a multifunctional bone repair scaffold was fabricated (Al@pNPs/Fg). The Al@pNPs/Fg exhibited three synergistic effects on the bone microenvironment: i) enhanced ectomesenchymal stem cell (EMSC) osteogenic differentiation by activating the piezo 1 channel; ii) inhibited the formation and function of osteoclasts related to the NF-κB signaling pathways; and iii) promoted M2 polarization and anti-inflammatory factor expression under normal and simulated inflammatory conditions. Al@pNPs/Fg ultimately promoted cranial bone defect regeneration in an SD rat model. This simple and low-cost technology provides a new approach to constructing an efficient delivery system and has desirable biological properties, providing a tissue-committed niche for the repair of bone defects.