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Background/Objectives: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association between serum chemerin levels and COVID-19 disease severity and outcomes has not been definitively established. Methods: In this study, serum chemerin levels were analyzed in 64 patients with moderate COVID-19 and 60 patients with severe disease. Results: The results showed that serum chemerin levels were comparable between these two groups and slightly higher than in healthy controls. Notably, COVID-19 patients with hypertension exhibited elevated serum chemerin levels, while those with liver cirrhosis had lower levels. When patients with these comorbidities were excluded from the analyses, serum chemerin levels in COVID-19 patients were similar to those in healthy controls. Positive correlations were observed between serum chemerin levels and markers such as alkaline phosphatase, C-reactive protein, eosinophils, and lymphocytes in the entire cohort, as well as in the subgroup excluding patients with hypertension and cirrhosis. Additionally, urinary chemerin levels were comparable between COVID-19 patients and controls, and neither hypertension nor dialysis significantly affected urinary chemerin levels. Both survivors and non-survivors had similar serum and urinary chemerin levels. Conclusions: In conclusion, this study suggests that comorbidities such as arterial hypertension and liver cirrhosis do have a more significant impact on serum chemerin levels than SARS-CoV-2 infection itself. [ABSTRACT FROM AUTHOR]

Chemerin, an adipokine known for its role in adipogenesis and inflammation, has emerged as a significant biomarker in cardiovascular diseases, including acute myocardial infarction (AMI). Recent studies have highlighted chemerin's involvement in the pathophysiological processes of coronary artery disease (CAD), where it modulates inflammatory responses, endothelial function, and vascular remodelling. Elevated levels of chemerin have been associated with adverse cardiovascular outcomes, including increased myocardial injury, left ventricular dysfunction, and heightened inflammatory states post-AMI. This manuscript aims to provide a comprehensive review of the current understanding of chemerin's role in AMI, detailing its molecular mechanisms, clinical implications, and potential as a biomarker for diagnosis and prognosis. Additionally, we explore the therapeutic prospects of targeting chemerin pathways to mitigate myocardial damage and improve clinical outcomes in AMI patients. By synthesizing the latest research findings, this review seeks to elucidate the multifaceted role of chemerin in AMI and its promise as a target for innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is characterized by elevated low‐density lipoprotein (LDL)‐cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol‐lowering with statins or proprotein convertase subtilisin‐kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL‐cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high‐density lipoprotein (HDL)‐cholesterol. Yet, only statins additionally reduced chemerin and high‐sensitivity C‐reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL2/HDL3 fractions, while >75% was free. Statins lowered both HDL‐bound and free chemerin. Pull‐down assays revealed that chemerin binds to the HDL‐component Apolipoprotein A‐I (ApoA‐I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL‐mediated cholesterol efflux via its chemerin chemokine‐like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA‐I and inhibits HDL‐mediated cholesterol efflux. Statins prevent this by lowering HDL‐bound chemerin. Combined with their anti‐inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i. [ABSTRACT FROM AUTHOR]

The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7- CD45RO+ effector memory, and CCR7- CD45RO- effector memory RA phenotypes, express the chemerin receptor CMKLR1 and bind chemerin via the receptor. CMKLR1-expressing human CD8 effector memory T cells present gene, protein, and cytotoxic features of NK cells. Active chemerin promotes chemotaxis of CMKLR1-expressing CD8 effector memory cells and triggers activation of the α4β1 integrin. In an experimental prostate tumor mouse model, chemerin expression is downregulated in the tumor microenvironment, which is associated with few tumor-infiltrating CD8+ T cells, while forced overexpression of chemerin by mouse prostate cancer cells leads to an accumulation of intra-tumor CD8+ T cells. Furthermore, α4 integrin blockade abrogated the chemerin-dependent recruitment of CD8+ T effector memory cells into implanted prostate tumors in vivo. The results identify a role for chemerin:CMKLR1 in defining a specialized NK-like CD8 T cell, and suggest the use of chemerin-dependent modalities to target effector CMKLR1-expressing T cells to the tumor microenvironment for immunotherapeutic purposes.

Background: Diabetes mellitus (DM) is a major public health concern worldwide. Although there are many possible causes of diabetes, the three most prevalent ones are insulin resistance, pancreatic cell damage, and insulin insufficiency. Visfatin, an adipocytokine with insulin-mimicking characteristics, and chemerin, an adipokine responsible for maintaining normal cholesterol and glucose levels, are linked to inflammation and immunological dysfunction in metabolic illnesses. Hence, in this study, we aimed to evaluate the possible association between type 2 diabetes mellitus (T2DM) and the adipokines visfatin and chemerin. Methods and Results: This study was conducted at the Al-Salam Teaching Hospital in Mosul from December 1, 2022, to the end of June 2023. The study included 65 patients of both sexes with T2DM aged between 35 and 80. Twenty-five healthy individuals of both sexes were chosen for a control group. Visfatin and chemerin levels in the serum were measured using an ELISA kit (Koma biotech, ELISA, USA) per the manufacturer's instructions. The levels of visfatin and chemerin in T2DM patients were significantly higher than in controls (1.478±0.631ng/ml and 158.768±36.941pg/ml vs. 0.538±0.151ng/ml and 71.272±12.994pg/ml, respectively, P=0.000 in both cases). The study showed no significant difference in the levels of chemerin and visfatin between females and males in T2DM patients. Among men, the visfatin levels were significantly higher in T2DM patients with diabetic retinopathy than in T2DM patients with such complications as cardiovascular disease and diabetic nephropathy. These features also occurred among women. Men and women with T2DM did not differ in the chemerin levels, depending on the nature of the diabetes complication. Conclusion: T2DM patients are characterized by significantly higher visfatin and chemerin levels than healthy controls. No differences in the levels of these adipokines that depend on the gender of diabetic patients have been found.

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood. [ABSTRACT FROM AUTHOR]

The adipokine chemerin contributes to exercise-induced improvements in glucose and lipid metabolism; however, the underlying mechanism remains unclear. We aimed to confirm the impact of reduced chemerin expression on exercise-induced improvement in glycolipid metabolism in male diabetic (DM) mice through exogenous chemerin administration. Furthermore, the underlying mechanism of chemerin involved in changes in muscle mitochondria function mediated by androgen/androgen receptor (AR) was explored by generating adipose-specific and global chemerin knockout (adipo-chemerin−/− and chemerin−/−) mice. DM mice were categorized into the DM, exercised DM (EDM), and EDM + chemerin supplementation groups. Adipo-chemerin−/− and chemerin−/− mice were classified in the sedentary or exercised groups and fed either a normal or high-fat diet. Exercise mice underwent a 6-wk aerobic exercise regimen. The serum testosterone and chemerin levels, glycolipid metabolism indices, mitochondrial function, and protein levels involved in mitochondrial biogenesis and dynamics were measured. Notably, exogenous chemerin reversed exercise-induced improvements in glycolipid metabolism, AR protein levels, mitochondrial biogenesis, and mitochondrial fusion in DM mice. Moreover, adipose-specific chemerin knockout improved glycolipid metabolism, enhanced exercise-induced increases in testosterone and AR levels in exercised mice, and alleviated the detrimental effects of a high-fat diet on mitochondrial morphology, biogenesis, and dynamics. Finally, similar improvements in glucose metabolism (but not lipid metabolism), mitochondrial function, and mitochondrial dynamics were observed in chemerin−/− mice. In conclusion, decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, likely through changes in androgen/AR signaling. NEW & NOTEWORTHY: Decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, which is likely mediated by androgen/androgen receptor expression. This study is the first to report the regulatory mechanism of chemerin in muscle mitochondria. [ABSTRACT FROM AUTHOR]

Abstract Hypercholesterolemia is characterized by elevated low‐density lipoprotein (LDL)‐cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol‐lowering with statins or proprotein convertase subtilisin‐kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL‐cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high‐density lipoprotein (HDL)‐cholesterol. Yet, only statins additionally reduced chemerin and high‐sensitivity C‐reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL2/HDL3 fractions, while >75% was free. Statins lowered both HDL‐bound and free chemerin. Pull‐down assays revealed that chemerin binds to the HDL‐component Apolipoprotein A‐I (ApoA‐I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL‐mediated cholesterol efflux via its chemerin chemokine‐like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA‐I and inhibits HDL‐mediated cholesterol efflux. Statins prevent this by lowering HDL‐bound chemerin. Combined with their anti‐inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i.

ABSTRACT: Embryonic mortality is a significant problem in the commercial duck industry worldwide. Therefore, identification of new biomarkers for duck embryo development is necessary. In the chicken (order Galliformes), we previously showed that chemerin is a hormone locally produced by the reproductive tract in hens, particularly in the magnum area, leading to its accumulation in the egg white and within the embryo annexes during embryonic development. We therefore hypothesized that the chemerin concentration in egg white could be a biomarker of egg performance and reproductive parameters in Pekin ducks (order Anseriformes). Thus, we collected eggs from Pekin ducks over a 5-d period at three stages of the laying period (before the laying peak, after the laying peak, and at the end of the laying period) to measure the chemerin concentrations in egg white by enzyme-linked immunosorbent assay. The chemerin concentration in egg white decreased during the laying period and was not associated with reproductive parameters. We found negative correlations between the chemerin level in egg white and the albumen weight. Reverse-transcriptase quantitative polymerase chain reaction showed that chemerin and its three receptors CMKLR1, GPR1, and CCRL2 were expressed in the reproductive tract and within allantoic and amniotic annexes during embryo development. Chemerin concentrations strongly increased in amniotic fluid on embryonic day 16 (ED16) when the egg white was transferred into the amniotic sac. Finally, chemerin inhibition in egg white by in ovo injections of anti-chemerin antibodies (0.01, 0.1, and 1 µg) increased the embryo mortality rate. These data demonstrate the important role of the chemerin system during egg formation and embryo development in Pekin ducks, suggesting their potential use as biomarkers for determining the quality of poultry eggs and embryo development.

Chemerin is a newly described adipokine with significant effects on obesity, metabolic disorders, and immune trafficking. Recently, chemerin has gained prominence for its potential roles in cancer and tumorigenesis with pro‐ or antitumor effects. To date, most referenced multifunctions of chemerin are attributed to the chemokine‐like receptor 1 (CMKLR1), distributing broadly in many tissues. This study investigates the in vitro roles of chemerin treatment on migration and invasion of ovarian carcinoma cells (OVCAR‐3 and SK‐OV‐3) and potential underlying mechanisms. Herein, exogenous chemerin treatment promotes growth and invasion of SK‐OV‐3 cells but has no significant effects on OVCAR‐3 cells. SK‐OV‐3 cells undergo morphological elongation characterized by epithelial‐to‐mesenchymal transition (EMT) and Ras homologous genome members A (RhoA)/Rho protein‐related curl spiral kinase‐1 (ROCK1) activation. Furthermore, chemerin‐enhanced invasion and EMT of SK‐OV‐3 cells are effectively blocked by C3 transferase (C3T) and Y27632 and RhoA and ROCK1 inhibitor, respectively. More importantly, RhoA/ROCK1‐EMT‐mediated SK‐OV‐3 cell invasion is orchestrated by CMKLR1 upregulation after chemerin treatment (50 ng/mL). The silencing of CMKLR1 significantly (P < 0.0001) reverses the chemerin‐enhanced invasion, EMT, and RhoA/ROCK1 activation of SK‐OV‐3 cells. Our study indicates that chemerin promotes invasion of OC cells via CMKLR1‐RhoA/ROCK1‐mediated EMT, offering a novel potential target for metastasis of OC. [ABSTRACT FROM AUTHOR]

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague–Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine‐like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin‐9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α‐NETA, superoxide scavenger tempol or N‐acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin‐9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin‐9 was inhibited by α‐NETA. The effects of cNTS microinjection of chemerin‐9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK‐801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin‐9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1‐mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin‐9‐induced responses. [ABSTRACT FROM AUTHOR]

Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92–199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing. [ABSTRACT FROM AUTHOR]

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity. β3-adrenoceptor (β3-AR), a type of G protein-coupled receptor (GPCR), is believed to mediate the thermogenesis of brown fat in mice. However, β3-AR has low expression in human adipose tissue, precluding its activation as a standalone clinical modality. This study aimed at identifying a potential GPCR target to induce beige fat. We found that chemerin chemokine-like receptor 1 (CMKLR1), one of the novel GPCRs, mediated the development of beige fat via its two ligands, chemerin and resolvin E1 (RvE1). The RvE1 levels were decreased in the obese mice, and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers. Inversely, despite sharing the same receptor as RvE1, the chemerin levels were increased in obesogenic conditions, and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers. Moreover, RvE1 and chemerin induced or restrained the development of beige fat, respectively, via the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1. In conclusion, our study showed that RvE1 and chemerin affected metabolic homeostasis differentially, suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

Adipokine chemerin plays important roles in disorders of glucose and lipid metabolism of obesity and obesity-related diseases, and exercise-induced improvement of glucose and lipid metabolism is closely related to the decrease of chemerin, but the mechanisms by which chemerin regulates glucose and lipid metabolism remain unclarified. Hypotestosterone induces male obesity and disorders of glucose and lipid metabolism through androgen receptor (AR) and its target genes: glucose and lipid metabolism-related molecules (including FOXO1, PEPCK, PGC-1α, and SCD1). Recently, the link between them has been reported that chemerin modulated the secretion of androgen. In this study, global chemerin knockout (chemerin (−/−)) mice were established to demonstrate the roles of chemerin in regulating blood glucose and blood lipid of mice under diet (high-fat (HFD) and normal diet) and exercise interventions and then to explore its mechanisms (AR – glucose and lipid metabolism enzymes). We found that the blood lipid and adipocyte size were low accompanied by the improvements in the levels of serum testosterone, gastrocnemius AR, and gastrocnemius FOXO1, SCD1, and PGC-1α in HFD chemerin (−/−) mice, but exercise-induced improvements of these indicators in HFD WT mice were attenuated or abolished in HFD chemerin (−/−) mice. In conclusion, the decrease of chemerin improved the blood lipid profile of HFD male mice at sedentary and exercise states, mediated partly by the increases of testosterone and AR to regulate glucose and lipid metabolism enzymes. To our knowledge, it is the first report that chemerin’s regulation of glucose and lipid metabolism might be mediated by testosterone and AR in vivo.

Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity. [ABSTRACT FROM AUTHOR]

Objective To study the role of perivascular adipose tissue (PVAT) in the reactivity of rat and human vessels.Methods Iliac and mesenteric arteries were obtained from normotensive Sprague-Dawley rats, hypertensive transgenic (mRen2)27 rats overexpressing mouse renin, and (mRen2)27 rats made diabetic with streptozotocin. Human coronary arteries were obtained from donors. Concentration-response curves were constructed to endothelin-1 and acetylcholine with and without PVAT. The contribution of NO and endothelium-dependent hyperpolarization (EDH) were determined making use of the NO synthase inhibitor L-NAME and the EDH inhibitors apamin + TRAM-34. The endothelin type A and type B (ETA, ETB) receptor blockers BQ123 and BQ788, the chemerin inhibitors α-NETA and pravastatin, and the angiotensin receptor blocker losartan were also used.Results In rat iliac arteries, PVAT diminished endothelin-induced constriction, while the opposite was true in human coronaries. Coronary effects were unaltered by α-NETA, pravastatin, or losartan. ETB receptor-mediated relaxation in iliac arteries occurred only with PVAT, and BQ123 blocked endothelin-1-induced constriction. Diabetes upregulated the anticontractile effects of PVAT. In rat mesenteric arteries, acetylcholine-induced relaxation with PVAT relied on NO, and on NO + EDH without PVAT. Diabetes upregulated the EDH component exclusively with PVAT.Conclusion PVAT modulates ET-1-induced constriction in a vessel type-dependent manner. Its enhancing effects in coronaries involved neither chemerin nor angiotensin II. Its anticontractile effects in rat iliac arteries involved ETB receptor-mediated relaxation. Diabetes upregulated PVAT’s anticontractile effects. In mesenteric arteries, PVAT counterbalanced the EDH component of the relaxant effect of acetylcholine. Diabetes reversed this effect by upregulating the EDH component.

Endovascular stenting is a safer alternative to open surgery for use in treating cerebral arterial stenosis and significantly reduces the recurrence of ischemic stroke, but the widely used bare-metal stents (BMSs) often result in in-stent restenosis (ISR). Although evidence suggests that drug-eluting stents are superior to BMSs in the short term, their long-term performances remain unknown. Herein, we propose a potential vascular stent modified by immobilizing clickable chemerin 15 (C15) peptides on the stent surface to suppress coagulation and restenosis. Various characterization techniques and an animal model were used to evaluate the surface properties of the modified stents and their effects on endothelial injury, platelet adhesion, and inflammation. The C15-immobilized stent could prevent restenosis by minimizing endothelial injury, promoting physiological healing, restraining the platelet-leukocyte-related inflammatory response, and inhibiting vascular smooth muscle cell proliferation and migration. Furthermore, in vivo studies demonstrated that the C15-immobilized stent mitigated inflammation, suppressed neointimal hyperplasia, and accelerated endothelial restoration. The use of surface-modified, anti-inflammatory, endothelium-friendly stents may be of benefit to patients with arterial stenosis. Endovascular stenting is increasingly used for cerebral arterial stenosis treatment, aiming to prevent and treat ischemic stroke. But an important accompanying complication is in-stent restenosis (ISR). Persistent inflammation has been established as a hallmark of ISR and anti-inflammation strategies in stent modification proved effective. Chemerin 15, an inflammatory resolution mediator with 15-aa peptide, was active at picomolar through cell surface receptor, no need to permeate cell membrane and involved in resolution of inflammation by inhibiting inflammatory cells adhesion, modulating macrophage polarization into protective phenotype, and reducing inflammatory factors release. The implications of this study are that C15 immobilized stent favors inflammation resolution and rapid re-endothelialization, and exhibits an inhibitory role of restenosis. As such, it helps the decreased incidence of ISR. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods: 120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils’ chemokines in OSCC using a real-time PCR, western blotting. Results: Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P

Chemerin is an atypical chemokine first described as a chemoattractant agent for monocytes, natural killer cells, plasmacytoid and myeloid dendritic cells, through interaction with its main receptor, the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been studied in various lung disease models, showing both pro- and anti-inflammatory properties. Given the incidence and burden of inflammatory lung diseases from diverse origins (infectious, autoimmune, age-related, etc.), chemerin has emerged as an interesting therapeutical target due to its immunomodulatory role. However, as highlighted by this review, further research efforts to elucidate the mechanisms governing chemerin's dual pro- and anti-inflammatory characteristics are urgently needed. Moreover, although a growing body of evidence suggests chemerin as a potential biomarker for the diagnosis and/or prognosis of inflammatory lung diseases, this review underscores the necessity for standardizing both sampling types and measurement techniques before drawing definitive conclusions. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is an inflammatory disease of paranasal sinuses. This study is formulated to explore the roles of pro‐inflammatory factors Chemerin and interleukin‐17 (IL‐17) in CRS. Patients suffering from CRS without/with nasal polyps (CRSsNP/CRSwNP), along with volunteers, were recruited. CRS rabbit models were constructed by Staphylococcus aureus infection and rabbits were injected with lentiviral vectors of short hairpin RNA‐targeting Chemerin (shChemerin), followed by micro‐computed tomography (CT) scan. Levels of Chemerin and IL‐17 were determined, and histopathological lesions were observed in subjects and CRS rabbits. Correlations between Chemerin/IL‐17 level and Lund‐Mackay/Lund‐Kennedy scores of subjects and the predictive value of Chemerin or IL‐17 for CRS were analyzed. In CRS patients and rabbits, inflammatory degrees and the level of Chemerin/IL‐17 were increased in pathological tissues or plasma, while Chemerin silencing alleviated CRS symptoms of CRS rabbits. Chemerin and IL‐17 were mainly located in the immune cells of pathological tissues and presented the positive correlation with Lund‐Mackay/Lund‐Kennedy score of CRS patients. Also, they showed high predictive value for CRS. Micro‐CT scan uncovered that CRS rabbits had increased bone remodeling, which was alleviated by Chemerin silencing. Collectively, Chemerin and IL‐17 are potential predictors and Chemerin silencing alleviates inflammatory response and bone remodeling in chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Diseases of the heart and blood vessels (CVD) are the leading cause of death worldwide, remaining an important concern for researchers, doctors, and patients alike. CVD encompasses a wide range of diseases that affect the heart, blood vessels, and blood. The study collected 80 blood serum samples, including 55 samples from patients with coronary artery disease and 25 healthy samples serving as a control group, collected from outpatient clinics in Samarra city from april 2023 to November 2023, with ages ranging from 25 to 55 years. The purpose was to evaluate the levels of chemerin, Superoxide Dismutase (SOD), Total Cholesterol (TC), Low-density lipoprotein (LDL-c), High-density lipoprotein (HDL-c), and Triglycerides (TG) in the coronary artery disease group and the control group. The results showed a significant increase (P ≤0.05) in chemerin, TC, LDL-c, and TG levels in the patient group compared to the control group, as well as a significant decrease (P ≤0.05) in SOD and (HDL-c) levels in the patient group compared to the control group. The area under the curve for chemerin and other measurements showed excellent accuracy in diagnosing the disease, in addition to high sensitivity and specificity, indicating the precision of the measurements as a diagnostic marker for the disease. [ABSTRACT FROM AUTHOR]

Recruitment and accumulation of reactive astrocytes around senile plaques are common pathological features of Alzheimer's disease (AD), with unclear mechanisms. Chemerin, an adipokine implicated in neuroinflammation, acts through its receptor, chemokine-like receptor 1 (CMKLR1), which also functions as a receptor for amyloid β (Aβ). The impact of the chemerin/CMKLR1 axis on astrocyte migration towards Aβ plaques is unknown. Here we investigated the effect of CMKLR1 on astrocyte migration around Aβ deposition in APP/PS1 mice with Cmklr1 knockout (APP/PS1-Cmklr1−/−). CMKLR1-expressed astrocytes were upregulated in the cortices and hippocampi of 9-month-old APP/PS1 mice. Chemerin mainly co-localized with neurons, and its expression was reduced in the brains of APP/PS1 mice, compared to WT mice. CMKLR1 deficiency decreased astrocyte colocalization with Aβ plaques in APP/PS1-Cmklr1−/− mice, compared to APP/PS1 mice. Activation of the chemerin/CMKLR1 axis promoted the migration of primary cultured astrocytes and U251 cells, and reduced astrocyte clustering induced by Aβ42. Mechanistic studies revealed that chemerin/CMKLR1 activation induced STING phosphorylation. Deletion of STING attenuated the promotion of the chemerin/CMKLR1 axis relative to astrocyte migration and abolished the inhibitory effect of chemerin on Aβ42-induced astrocyte clustering. These findings suggest the involvement of the chemerin/CMKLR1/STING pathway in the regulation of astrocyte migration and recruitment to Aβ plaques/Aβ42. [ABSTRACT FROM AUTHOR]

Context A subset of polycystic ovary syndrome (PCOS) individuals also have type 2 diabetes (T2D); an unmet need to identify this subgroup exists. Objective We looked at the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS. Methods A total of 93 PCOS and 33 healthy controls were classified, based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A1c (HbA1c) (%) into normoglycemic (n = 34), dysglycemic (n = 33), and T2D (n = 26). Serum chemerin were measured by enzyme-linked immunosorbent assay. Homeostatic model 2 assessment of insulin resistance (HOMA-2IR) and homeostatic model 2 assessment of β-cell function (HOMA-2β) were computed using serum C-peptide. Results Metabolic syndrome was present in 9.7% (National Cholesterol Education Program) of PCOS. Waist circumference, body fat (%), 2hPGPG, and HbA1c levels were significantly higher in T2D group. Serum triglycerides/high-density lipoprotein cholesterol (TGs/HDL-c) ratio was increased in PCOS individuals with T2D; no significant changes in total cholesterol and LDL-c levels were seen. Serum chemerin levels were significantly higher (P <.001) in the PCOS group. Total body fat (%), 2hPGPG, HbA1c, and TG/HDL-c ratio correlated positively with chemerin levels. Serum chemerin levels correlated positively with HOMA2IR and negatively with HOMA-2β. On receiver operating characteristic curve analysis, a serum chemerin cutoff level of greater than 309.3 ng/mL differentiated PCOS individuals with dysglycemia from those without (sensitivity 85.71%, specificity 89.47%). The Cohen kappa test revealed a substantial agreement (P <.001) between chemerin cutoff and 2hPGPG levels greater than 200 mg/dL. The present study is arguably the first ever to define a serum chemerin cutoff to distinguish PCOS individuals with T2D from those without. Conclusion Elevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Further, longitudinal studies with larger samples are required to confirm this association. [ABSTRACT FROM AUTHOR]

Abstract Oxidative stress has a significant impact on the etiology of type 1 diabetes mellitus (T1DM). However, associations of adipokines with oxidative stress biomarkers have yet to be investigated. Therefore, the present study aimed to investigate the estimation of serum apelin, chemerin, and omentin levels in induced TIDM and their correlations with oxidative stress markers. The study included sixty male albino rats divided into two groups. The first group (n = 30) was diabetic (TIDM induced with an intraperitoneal injection of 40mg/kg STZ). The non-diabetic control group was the second (n: 30). The enzyme-linked immunosorbent (ELISA) test was used to quantify the serum levels of apelin, chemerin, omentin and asymmetric dimethylarginine (ADMA). Furthermore, blood glucose, lipid profile triglyceride (TG), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), liver enzymes (alanine aminotransferase (ALT) and aspartate transaminase (AST)), malondialdehyde (MDA) and nitric oxide (NO) parameters were evaluated. Rats with induced TIDM had significantly higher serum levels of apelin, chemerin, omentin, malondialdehyde MDA, ADMA, and NO compared to non-diabetics. According to the coefficient of correlation analysis, the results revealed a positive association between apelin and LDL, ALT, and MDA and a negative correlation between apelin and AST: ALT. In addition, no correlation was found between apelin and serum levels of glucose, cholesterol, HDL, LDL: HDL TG, TG: HDL, VLDL, AST, creatinine, uric acid, albumin, NO, and ADMA. LDL, ALT, and MDA. Serum chemerin level correlated positively with LD: HDL and ADMA. Also, the plasma level of omentin showed a significant and positive correlation with both TG: HDL and MDA values. In conclusion, the results of this study introduced apelin and chemerin as potential biomarkers for the early detection of diabetes. Elevated serum apelin levels in induced T1DM could provide compensatory action for low insulin levels. While, apelin, chemerin and omentin’s positive correlations with MDA level suggest the potential roles of these adipokines in diabetes-induced complications caused by oxidative stress.

Abstract Neutrophil reverse migration (rM) is a recently identified phenomenon in which neutrophils migrate away from the inflammatory site back into the vasculature following initial infiltration, which involved in the resolution of loci inflammatory response or dissemination of inflammation. Present study was aimed to explore the mechanisms in neutrophil rM. By scRNA-seq on the white blood cells in acute lung injury model, we found rM-ed neutrophils exhibited increased gene expression of C–C motif chemokine receptor-like 2 (Ccrl2), an atypical chemokine receptor. Furthermore, an air pouch model was established to directly track rM-ed neutrophils in vivo. Air pouches were generated by 3 ml filtered sterile air injected subcutaneously for 3 days, and then LPS (2 mg/kg) was injected into the pouches to mimic the inflammatory state. For the rM-ed neutrophil tracking system, cell tracker CMFDA were injected into the air pouch to stain the inflammatory loci cells, and after 6 h, stained cells in blood were regarded as the rM-ed neutrophil. Based on this tracking system, we confirmed that rM-ed neutrophils showed increased CCRL2. We also found that the concentrations of the CCRL2 ligand chemerin in plasma was increased in the late stage. Neutralizing chemerin decreased the rM-ed neutrophil ratio in the blood. These results suggest that circulating chemerin attracts neutrophils to leave inflammatory sites by interacting with CCRL2, which might involve in the dissemination of inflammation.

Abstract Background Preeclampsia (PE) is a new-onset pregnancy-specific disorder with a high prevalence that leads to over 70 000 maternal and 500 000 foetal fatalities worldwide each year. The level of chemerin, a newly identified adipokine, is increased in diabetic and obese patients. Currently, there are several studies describing the relationship between maternal circulating chemerin levels and PE. Therefore, this study aimed to assess their association in pooled samples. Methods Four databases were systematically searched to identify potential studies that reported circulating chemerin levels in PE and normal pregnancy groups. Standardized mean differences (SMDs), 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated using a random-effects meta-analysis. The probability of heterogeneity was also investigated by sensitivity analysis, subgroup analysis, and meta-regression. Results Thirteen studies in 11 articles with a total of 860 PE patients and 1309 women with normal pregnancies met the inclusion criteria. The results of the meta-analysis revealed that circulating chemerin, which levels in PE patients were considerably higher than those in controls (SMD = 1.39, 95% CI: 1.02, 1.77, 95% PI: -0.07, 2.86). Moreover, sensitivity analysis determined that the outcomes of the overall pooled results were not affected after the elimination of any study. Notably, subgroup analysis demonstrated a similar expression pattern irrespective of geographic location, severity, timing of sampling, and sample size. Last, there were no factors that significantly impacted the overall estimate, according to meta-regression. Conclusions This meta-analysis is the first to assess circulating chemerin levels in PE patients. The findings indicate that circulating chemerin levels may be a potential marker to diagnose PE.

Abstract We executed this study to determine if chemerin‐like receptor 1 (CMKLR1), a Gi/o protein‐coupled receptor expressed by leukocytes and non‐leukocytes, contributes to the development of phenotypic features of non‐atopic asthma, including airway hyperresponsiveness (AHR) to acetyl‐β‐methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non‐atopic asthma in wild‐type mice and mice incapable of expressing CMKLR1 (CMKLR1‐deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O3), a criteria pollutant and non‐atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi‐functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1‐deficient as compared to wild‐type mice. Regardless of genotype, exposure to O3 caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype‐related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype‐related differences following O3 exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O3.

ABSTRACT: Intensive genetic selection of broiler breeders and layer hens resulted in differences in the mechanisms of growth and also in cell metabolism during embryogenesis. Previous research has shown that an adipokine named chemerin and one of these receptors, CMKLR1 were potentially involved in broiler embryo development. Here, our objectives were 1) to compare the expression of chemerin and its receptors CMKLR1, GPR1, and CCRL2 and chemerin concentration in extra-embryonic annexes (allantoic and amniotic membranes and fluids and plasma) in broiler and layer fertile eggs during the development (embryonic day (ED) 7, 14, and 18) by RT-qPCR and specific chicken ELISA and 2) to investigate the role of chemerin and one of its receptors GPR1 in embryo development after in ovo injections of neutralizing antibodies against chicken chemerin and GPR1. We found that chemerin expression in amniotic membranes was higher in layer than broiler eggs at ED7 and ED14 whereas the expression of the 3 receptors was higher in layer than broiler in the allantoic membranes at ED14 and ED18. Chemerin concentration was more important in layer than broiler at ED14 and ED18 in amniotic liquid and at all the studied stages in blood plasma. We also showed positive correlation between amniotic chemerin concentration and chemerin amniotic membrane expression, chemerin plasma concentration and embryo body weight in both breeds. Finally, in ovo injection of chicken chemerin and GPR1 neutralizing antibodies increased embryo mortality in both layer and broiler eggs. Taken together, even if chemerin concentration and chemerin system expression in embryonic membranes are mainly higher expressed in layer than in broiler, chemerin potentially through GPR1 could promote embryo development in both breeds.

The pleiotropic chemokine chemerin is involved in multiple processes in metabolism and inflammation. The present study aimed to elucidate its regulation in morbid obesity and during therapy-induced rapid weight loss. A total of 128 severely obese patients were enrolled, and their basal anthropometric and clinical parameters were assessed. In total, 64 individuals attended a conservative 12-month weight loss program that included a low calorie-formula diet (LCD), and 64 patients underwent bariatric surgery (Roux-en-Y gastric bypass, RYGB). Blood serum was obtained at study baseline and at follow-up visits after 3, 6, and 12 months. Systemic chemerin concentrations, as well as metabolic and immunological parameters, were quantified. During the 12-month period studied, serum chemerin levels decreased significantly with weight loss after bariatric surgery, as well as with conservative low calorie therapy; however, the effects of RYGB were generally stronger. No substantial associations of systemic chemerin concentrations with therapy-induced improvement of type 2 diabetes and with indicators of liver function and fibrosis were observed. We conclude that systemic chemerin levels decrease in obese individuals during weight loss, regardless of the therapeutic strategy. A potential involvement in weight loss-associated improvement of metabolic disorders and liver fibrosis remains to be further investigated. [ABSTRACT FROM AUTHOR]