Search Results (173)

Extracellular vesicles (EVs), particularly exosomes, are key mediators of intercellular communication, transporting biomolecules such as nucleic acids, lipids, and proteins that influence immune and metabolic pathways. In adipose tissue (AT), adipocyte-derived EVs (AdEVs) play a crucial role in maintaining metabolic homeostasis and have been implicated in obesity-related dysfunction. Among their bioactive cargo, microRNAs regulate post-transcriptional gene expression and participate in immunometabolic regulation. This study aimed to determine whether miR-34a expression in serum and circulating EVs varies according to body fat percentage, to explore its potential utility as a non-invasive biomarker of AT dysfunction. A total of 142 adults (mean age 36 ± 11 years) were classified by body fat percentage (≥25% in men, ≥35% in women). Exosomes were isolated (Invitrogen^®) and characterized by cryo-TEM, and miR-34a expression was quantified by qRT-PCR. miR-34a expression correlated negatively with Total Cholesterol, Triglycerides, LDLc/HDLc, TG/HDLc, BMI, C3, CRP, fasting insulin, HOMA-IR, HOMA-B, Body adiposity, Chemerin, CCL2, AdipoQT, and AdipoQ-H, but positively with HDLc and QUICKI. Notably, LDLc, sdLDLc, sdLDLc/LDLc, TC/HDLc, and fasting glucose showed opposite correlation patterns between serum and exosomes. Overall, serum miR-34a levels were higher than in exosomes, suggesting its potential as a biomarker of metabolic dysfunction and insulin resistance. Full article

Infertility is a widespread global problem, with a male factor contributing to approximately 40–50% of cases. Several studies have investigated the involvement of adipokines in reproductive functions, but only a few have investigated their role in the male reproductive component. Collectively, adipokines are present in human sperm and most of them are expressed in the male genital tract. Some authors report that adiponectin, in contrast with other adipokines such as resistin or chemerin, has a positive effect on spermatogenesis. Although the pathophysiological role of adipokines in sperm is not yet fully understood, they could influence sperm functionality and could be potential biomarkers of male fertility. High levels of sperm DNA fragmentation have been associated with several adverse reproductive outcomes, although studies have shown conflicting results. Another critical factor in male infertility is oxidative stress, which negatively affects sperm function and viability, also because it triggers DNA alterations, lipid peroxidation and alterations in protein expression, compromising fertilization potential. To better understand the correlation between sperm DNA fragmentation, adiponectin and oxidative stress and their role in clinical practice, we evaluated these parameters in the seminal plasma of males who presented to the infertility study center of Careggi University Hospital of Florence. By accurately evaluating these parameters and their possible correlation, it will be possible to personalize treatment for individual patients. Full article

Depression and obesity are amongst the most serious global health challenges. Each of them is associated with high morbidity, chronicity, and socioeconomic burden. Increasing evidence suggests that these conditions are not merely comorbid but share convergent biological pathways (e.g., hypothalamic–pituitary–adrenal axis dysregulation, chronic inflammation, gut dysbiosis, and mitochondrial dysfunction). All these components contribute together to the development and persistence of depressive symptoms as well as to an increase in adiposity. Within this framework, adipose tissue has emerged as an essential endocrine organ that has a deep impact on neuroimmune signalling and mood regulation through its secreted molecules, such as leptin, adiponectin, resistin, omentin, apelin, chemerin, and visfatin. The current management of depression involves a comprehensive, multidisciplinary approach that includes pharmacological treatment and psychotherapeutic support, alongside lifestyle changes. Here we highlight the molecular crosstalk between adipose tissue and the brain, summarising the evidence of adipokines’ dysregulation role in connecting metabolic dysfunction to depressive neurobiology. By integrating metabolic, immunological, and neuroendocrine perspectives, this narrative review underscores the need to reconceptualise depression as an immunometabolic disorder. Understanding adipokine-mediated pathways may reveal new biomarkers and therapeutic targets, fostering interdisciplinary approaches. This would allow for the development of new treatment strategies, which include recombinant adipokines, anti-inflammatory agents, and microbial modulation. These new strategies might provide a significant benefit in selected patients, in addition to conventional antidepressants. Full article

Background and Objectives: Multiple myeloma (MM) remains an incurable plasma cell malignancy with heterogeneous clinical outcomes. Although current prognostic systems integrate biochemical and cytogenetic parameters, they do not fully capture disease complexity. Adipocytes within the bone marrow microenvironment secrete adipokines that regulate inflammation, metabolism, and immune interactions and may influence disease progression. This study aimed to assess circulating adipokines and related microenvironmental mediators as potential biomarkers of disease activity and treatment response in MM. Materials and Methods: In this case–control, cross-sectional study, the serum levels of eight adipokine-related molecules—adiponectin, leptin, resistin, chemerin, adipsin, thrombospondin-1 (TSP-1), paraoxonase-1 (PON-1), and myeloperoxidase (MPO)—were measured in 40 MM patients and 38 age- and sex-matched healthy controls. Enzyme-linked immunosorbent assays (ELISA) and bead-based multiplex immunoassays were used. Associations with prognostic markers (serum β₂-microglobulin (sB2M), LDH, albumin, hemoglobin, renal function) and treatment response were analyzed using correlation and non-parametric statistical methods. Results: Compared to the controls, MM patients exhibited significantly higher circulating levels of adiponectin, resistin, chemerin, adipsin, TSP-1, and MPO, while leptin was decreased. Among clinical correlations, chemerin and PON-1 correlated positively with sB2M, TSP-1 correlated with LDH, and MPO correlated with M-protein and albumin. Resistin was lower in patients with renal impairment and an advanced disease stage. Adiponectin and TSP-1 were significantly lower in progressive disease compared to complete remission, suggesting their potential association with treatment response. Conclusions: This study demonstrates that multiple adipokines are dysregulated in MM and exhibit distinct associations with disease burden, renal function, and therapeutic response. Novel associations identified for TSP-1, PON-1, and adipsin highlight previously unrecognized microenvironmental pathways in MM biology. Adipokine profiling may complement established prognostic markers and provide new insights into the tumour microenvironment in MM. Full article

Background/Objectives: The global prevalence of obesity and type 2 diabetes mellitus (T2DM) has been steadily increasing, and these interrelated disorders share common pathophysiological mechanisms, including altered levels of adipokines secreted from adipose tissue. Among these, chemerin and visfatin have been suggested as potential biomarkers for obesity-related metabolic dysfunction. This study aimed to evaluate the relationship between serum chemerin and visfatin levels and obesity in patients with T2DM. Methods: The study included 74 obese T2DM patients, 60 non-obese T2DM patients, and 36 healthy controls. Serum chemerin and visfatin levels were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical parameters including HbA1c, fasting plasma glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were assessed. Between-group comparisons were performed using appropriate parametric or non-parametric tests with Bonferroni correction for multiple comparisons. ROC curve analysis was applied to evaluate the diagnostic performance of visfatin. Results: Serum visfatin levels were significantly higher in the T2DM (33.00 ± 20.61) groups compared to controls (30.25 ± 26.40; p = 0.01), while chemerin levels showed no significant difference. HbA1c and glucose levels were elevated in both diabetic groups, whereas insulin and HOMA-IR were significantly higher only in the obese T2DM group. Receiver operating characteristic (ROC) analysis revealed limited diagnostic accuracy of visfatin (AUC < 0.70). Conclusions: Visfatin levels were modestly higher in obese T2DM patients, while chemerin did not differ significantly among groups. However, the diagnostic performance of visfatin was limited (AUC < 0.70), and these findings should be regarded as exploratory. Larger, well-controlled studies are required to clarify whether visfatin or chemerin could have any clinical utility as part of multi-marker approaches. Full article

Chemerin, encoded by the RARRES2 gene, is an adipokine with potent immunometabolic functions mediated through CMKLR1, GPR1, and CCRL2. Its regulation is tissue- and context-dependent, conferring dual protective and pathogenic roles. In the upper GI tract, chemerin facilitates immune tolerance in Barrett’s adenocarcinoma and promotes invasion in esophageal and gastric cancers. In pancreatic disease, it acts as a biomarker of acute and chronic injury, while modulating β-cell function and carcinogenesis. In the liver, chemerin contributes to NAFLD/NASH pathogenesis with both anti-inflammatory and pro-steatotic actions, predicts prognosis in cirrhosis, and demonstrates tumor-suppressive potential in hepatocellular carcinoma. In IBD, chemerin exacerbates colitis via impaired macrophage polarization, yet protects epithelial antimicrobial defense, underscoring its context-specific biology. Collectively, these findings position chemerin as a versatile regulator bridging metabolic dysfunction, inflammation, and gastrointestinal malignancy, and as a potential candidate for biomarker development and therapeutic intervention. Full article

Pulmonary fibrosis is a progressive interstitial lung disease that involves stimulated growth of fibroblasts, over-deposition of extracellular matrix (ECM), and permanent damage of the lung structure. Among its various forms, idiopathic pulmonary fibrosis (IPF) is the most common and life-threatening type with few treatment options and a poor prognosis. Such obstacles highlight the urgency to find new molecular targets by better understanding the cellular and signaling processes that contribute to the pathogenesis of the disease. Chemerin is an adipokine and chemoattractant protein that has recently come into the limelight as a major controller of immune cell trafficking, inflammation, and tissue remodeling. Its biological activity is mainly mediated by binding to its receptors Chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C chemokine receptor-like 2 (CCRL2), and has been linked to numerous pathological conditions, such as metabolic diseases, cancer, and inflammatory diseases. Emerging data now indicate that chemerin can also be a key factor in the initiation and progression of pulmonary fibrosis. The aim of the review is to overview the existing evidence regarding regulatory processes of chemerin expression, signaling pathways, and effects of this protein in cells in the fibrotic lung microenvironment. Moreover, we will comment on the findings of in vitro and in vivo experiments supporting the possibility of chemerin as a promising molecular target in basic research on pulmonary fibrosis. Full article

Obesity is a multifactorial disease with endocrine, metabolic, and inflammatory underpinnings, leading to numerous comorbidities and increased mortality. This has driven research into adipose tissue’s role as an endocrine organ that secretes adipokines. This review critically analyzes three of these adipokines: chemerin, omentin-1, and visfatin. Chemerin and omentin-1 have well-defined roles as pro- and anti-inflammatory mediators, respectively. However, the function of visfatin remains controversial, with conflicting data regarding its role in glucose metabolism and inflammation. This conflicting evidence highlights an urgent need for standardized assays and population-specific studies to clarify its true function. We conclude that while chemerin and omentin-1 represent promising targets, the ambiguity surrounding visfatin limits its current clinical utility, and resolving these knowledge gaps is essential for developing effective biomarkers and therapies for obesity and its comorbidities. Full article

Background/Objectives: The remodeling of adipose tissue occurring in obesity is associated with dysregulated production of various adipokines with vasoactive properties. Among the local mediators physiologically involved in vascular homeostasis, the endothelin (ET-1) system is upregulated in obesity, leading to vasoconstriction and vascular damage. We hypothesized that in human obesity, a link might exist between changed circulating levels of vasoactive adipokines and ET-1-dependent vasoconstriction; Methods: We compared plasma concentrations of selected adipokines (Luminex assay) and the vasoactive response to blockade of endothelin type A receptors (ET_A) by BQ-123 (strain-gauge plethysmography) in lean and obese individuals; Results: Plasma levels of adipokines with deleterious vascular actions, such as chemerin, visfatin, adipsin, and leptin, were higher in obese than in lean subjects (all p < 0.05). In contrast, circulating adiponectin, an adipokine with vasoprotective properties, showed no difference between groups (p > 0.05). The blood flow response to BQ-123 was greater in obese subjects than in lean subjects (p < 0.001), indicating an obesity-associated enhancement in ET-1-mediated vasoconstriction. In the entire population, circulating chemerin showed a direct correlation with the vasodilator response to BQ-123 (r = 0.30; p = 0.01). In contrast, no significant correlation was observed between concentrations of other adipokines and the response to BQ-123 (all p > 0.05). Conclusions: In human obesity, a direct link exists between increased circulating chemerin and augmented ET-1-mediated vasoconstriction. This observation contributes to explaining the detrimental vascular actions of chemerin and supports the view that targeting this adipokine might help prevent obesity-related vasculopathy. Full article

Oral cancer (OC) constitutes a significant health problem globally. There is an urgent need to develop novel biomarkers for OC diagnosis. This meta-analysis aimed to analyze the potential of salivary lactate dehydrogenase (LDH), matrix metalloproteinase-9 (MMP-9), and chemerin as OC biomarkers. The meta-analysis was conducted according to the PRISMA statement guidelines and registered in PROSPERO (CRD420251045968). PubMed, Embase, Scopus, and Web of Science databases were thoroughly searched up to 18 April 2025. After screening, thirty-three articles were included in the meta-analysis based on the random-effects model. The meta-analysis revealed a significantly elevated LDH level in OC patients compared with controls (SMD = 4.592, 95% CI: 3.580–5.605, p < 0.001) and with oral potentially malignant disorders (OPMD) (SMD = 2.416, 95% CI: 1.474–3.358, p < 0.001). For poorly versus well-differentiated OC, significantly higher LDH levels were observed in poorly differentiated tumors (SMD = 6.158, 95% CI: 0.739–11.576, p = 0.027). For MMP-9, there was a significant increase in OC compared with controls and a borderline-significant difference compared with OPMD (SMD = 1.507, 95% CI: 0.644–2.369, p = 0.001; SMD = 1.626, 95% CI: −0.097–3.350, p = 0.064, respectively). In comparing poorly versus well-differentiated OC, MMP-9 levels were significantly increased in poorly differentiated tumors (SMD = 1.790, 95% CI: 0.643–2.937, p = 0.003). Chemerin levels were significantly elevated in OC versus controls (SMD = 3.905, 95% CI: 3.210–4.600, p < 0.001) and OPMD (SMD = 1.605, 95% CI: 1.139–2.071, p < 0.001). In conclusion, these findings support the potential use of LDH, MMP-9, and chemerin as adjunctive biomarkers in diagnosing and stratifying OC. Full article

Colorectal cancer (CRC) stands as one of the most prevalent and lethal forms of cancer worldwide with early detection playing a crucial role in improving the survival rate. Salivary biomarkers have emerged as a promising non-invasive alternative for CRC early detection. A comprehensive search of the Web of Science, Scopus, and PubMed databases was performed to identify relevant studies published between 2018 and April 2025. Inclusion criteria focused on studies analyzing salivary biomarkers in adult CRC patients, while pediatric studies, non-diagnostic applications, and studies with insufficient statistical power were excluded. A total of 12 studies were included in this review, identifying various salivary biomarkers associated with CRC. Salivary microbiota, including Fusobacterium nucleatum and other bacterial species, demonstrated potential as diagnostic markers. Metabolomic profiling revealed elevated levels of lactate and pyruvate, reflecting metabolic alterations in CRC. Several microRNAs, such as miR-92a and miR-29a, exhibited high sensitivity and specificity for CRC detection. Additionally, protein-based biomarkers, including chemerin and sHLA-G, were found to be significantly elevated in CRC patients. Salivary biomarkers show great promise as a non-invasive, cost-effective approach for CRC detection and prognosis. Their ability to reflect systemic disease processes makes them a valuable complement to existing screening methods. Full article

C-C motif chemokine receptor-like 2 (CCRL2) is an atypical chemokine receptor (ACKR) that binds chemerin with high affinity but lacks classical G protein-coupled signaling. Instead, it functions as a non-signaling presenter of chemerin to CMKLR1-expressing cells, modulating antitumor immunity. CCRL2 is highly expressed in the tumor microenvironment and various human cancers, and its expression has been linked to delayed tumor growth in mouse models, primarily through the chemerin/CMKLR1 axis. While CCRL2’s role in immune surveillance is well established, its tumor cell-intrinsic functions remain less clear. Here, we investigated the impact of CCRL2 overexpression and knockout on tumor cell behavior in vitro. Although CCRL2 did not affect proliferation, migration, or clonogenicity in B16F0 melanoma and LLC cells, it significantly influenced spheroid morphology in B16F0 cells. Transcriptomic analysis revealed that CCRL2 modulates innate immune signaling pathways, including TLR4 and IFN-γ/STAT1, with context-dependent downstream effects. These findings suggest that CCRL2 shapes tumor architecture by rewiring inflammatory signaling networks in a cell-intrinsic manner. Further studies in other cancer types and cell models are needed to determine whether CCRL2’s regulatory role is broadly conserved and to explore its potential as a therapeutic target in solid tumors. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article

Chemerin is an adipokine that is associated with insulin resistance, a feature well marked in gestational diabetes mellitus (GDM). Recent publications and meta-analyses investigating chemerin levels in GDM remain inconclusive. This updated systematic review and meta-analysis aims to update the current evidence of an association between chemerin and GDM. The databases PubMed, ScienceDirect, and Google Scholar were searched for eligible articles from their inception up to 1 April 2025. Pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) of the chemerin levels between GDM cases and normoglycemic controls were calculated using the “meta” package in “R” software. Twenty-two studies were included in this meta-analysis, comprising a total of 1735 GDM cases and 1701 normoglycemic pregnant controls. Due to significant heterogeneity, a random effects model was applied, and the chemerin levels were found to be significantly higher in cases compared to normoglycemic controls [SMD = 0.97, 95% CI (0.16; 1.78) ng/mL; p = 0.020]. Subgroup analysis showed that studies conducted in Asia, studies utilizing a case–control design, patients younger than 30 years, and patients with a BMI less than 28 showed significantly higher chemerin levels in cases compared to controls. Meta-regression analysis indicated that only patients over 30 years old showed a negative association with chemerin levels. No evidence of publication bias was observed. This updated meta-analysis confirmed that chemerin levels are elevated in cases of GDM, which may indicate its involvement in the pathogenesis of GDM. Further longitudinal studies are needed to consolidate this finding. Full article

Psoriasis is a chronic, immune-mediated inflammatory skin disease with complex genetic, environmental, and immunological determinants. Beyond the skin, it affects multiple systems, including the joints and cardiovascular system. A hallmark of psoriasis is an overactivation of the innate and adaptive immune responses, leading to dysregulated cytokine signaling, altered keratinocyte function, and aberrant expression of structural and regulatory proteins. In recent years, growing attention has been given to the skin as a neuro–immuno–endocrine organ, with evidence showing the role of stress-related neuropeptides, UVB-induced immune modulation, and vitamin D signaling in the disease pathogenesis. This review highlights emerging evidence on key multifunctional proteins—elafin, chemerin, and NAMPT (visfatin)—that exert both pro- and anti-inflammatory actions. Although still underexplored, these molecules appear to contribute significantly to the psoriatic microenvironment by modulating inflammation, immunity, and skin barrier function. Their dual roles suggest complex interactions within the cutaneous immune–neuroendocrine network, positioning them as potential biomarkers or therapeutic targets in psoriasis. By integrating insights into classical and emerging mediators, this review aims to provide a comprehensive perspective on the evolving landscape of psoriasis pathophysiology. Full article