Gas6/TAM system as potential biomarker for multiple sclerosis prognosis.

Introduction: The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity. Methods: In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay. Results: At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS <3 at diagnosis (p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (p = 0.005; p = 0.002) and MSSS (r2 = 0.27, p = 0.03; r2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis. Conclusions: Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

High dose statin treatment reduces circulating Dickkopf-1 following acute myocardial infarction.

BACKGROUND: Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known. METHODS: We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; n = 25) and moderate dose (20 mg simvastatin, given the day after PCI; n = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed. RESULTS: (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of ß-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. (iii) DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC. CONCLUSIONS: Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients.

Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels are decreased in patients with Behçet's disease.

PURPOSE: Behçet's disease (BD) is an autoimmune chronic systemic inflammatory disease characterized by a versatile clinical spectrum. Growth arrest specific protein 6 (GAS6)/soluble AXL (sAXL) signaling pathway draws attention in the resolution of inflammation, and its deficiency is associated with chronic inflammatory, autoimmune diseases, as well as clearance of apoptotic cells by phagocytes - efferocytosis. In this study, it was aimed to investigate whether GAS6/sAXL, interleukin (IL)-10, nitric oxide (NO), and BCL-2 levels were associated with inflammation and efferocytosis contributes to the pathogenesis of BD. METHODS: A total of 37 Behçet patients with ocular involvement and 30 healthy control subjects were included in this study. GAS6, sAXL, IL-10, NO, and BCL-2 levels were quantified using enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels were significantly lower in patients with BD compared to the controls (P < 0.005, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). In correlation analysis, research parameters decreased in patients with BD was significantly correlated with each other: GAS6-IL-10 (r = 0.585, P < 0.001), GAS6-BCL-2 (r = 0.541, P < 0.001), sAXL-BCL-2 (r = 0.696, P < 0.001), IL-10-NO (r = 0.717, P < 0.001), IL-10-BCL-2 (r = 0.759, P < 0.001), and NO-BCL-2 (r = 0.541, P < 0.001). CONCLUSION: In conclusion, decreased serum BCL-2 level may be an indicator of increased apoptosis in these patients and decreased levels of GAS6/sAXL, IL-10, and NO may indicate insufficient clearance of apoptotic bodies released as a result of increased apoptosis in BD patients.

Evaluation of preadipocyte factor-1 (Pref-1) level in cord blood of newborns born by mothers with gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication, which leads to short and long-term consequences in both mother and fetus exposed to hyperglycemia. The aetiology of this condition is proposed to be based on the dysfunction of the adipose tissue, which is characterised by the aberrant generation of adipokines. One of them is preadipocyte factor-1 (Pref-1), which could mediate controlling the adaptation of the maternal metabolism to pregnancy. AIMS: The study aims to examine the level of Pref-1 in the cord blood of healthy pregnant women's neonates and fetuses born to mothers with GDM. MATERIALS AND METHODS: Cord blood samples were collected from 30 newborns of mothers with GDM and 40 newborns of healthy pregnant women. Pref-1 concentrations were measured with an ELISA kit. RESULTS: Fetal Pref-1 concentrations were significantly lower in newborns of mothers with GDM compared to the normal pregnancy group children (5.32 ± 0.29 vs. 7.38 ± 0.53; p < 0.001). Mothers with GDM had a significantly higher index of BMI before pregnancy, maternal gestational weight gain, and maternal fasting glucose. In-depth analysis through multiple variant linear regression revealed a significant association between fetal serum Pref-1 levels, exposure to GDM, and gestational age. CONCLUSION: These findings contribute valuable insights into maternal-fetal health and pave the way for more targeted and effective clinical interventions.

Blood Interleukin-18 (IL-18) and IL-18 Binding Protein (IL-18BP) Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

BACKGROUND/AIM: The acute phase immune response (APR) in midline laparotomy (MLa) patients following surgery has been rarely studied, with no studies assessing the association of blood IL-18 (interleukin-18) and IL-18BP (IL-18 binding protein) values with the numeric rating scale (NRS) pain score following MLa. PATIENTS AND METHODS: Blood levels of seven cytokines (CYT) (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1ß) and high-sensitivity C-reactive protein (hs-CRP) were measured at three time points; before operation (PRE), immediately after operation (POP1), and 24 h after operation (POP2) in 56 patients with MLa. The satisfaction of the patients at 24 h following MLa (SFS24; 0=fully unsatisfied; 10=fully satisfied) was recorded on a 11-point numeric rating scale. RESULTS: In all patients, the IL-18 and IL-18BP blood levels decreased at POP1 and the drop between the preoperative and POP1 levels in the IL-18 and IL-18BP was highly significant (p<0.001). However, the median IL-18 and IL-18BP blood levels increased significantly at POP2 (p<0.001) with the linear mixed-effect model (LME) showing a statistically significant time effect (p<0.001). The hs-CRP blood levels increased significantly at POP2 with the LME model showing a statistically significant time effect. The preoperative and POP2 IL-18 values were clearly higher in patients with cancer versus benign disease (177/182 vs. 135/126, p=0.039/p=0.013, respectively). Interestingly, in all patients of the study, the median IL-18 versus IL-18BP blood levels correlated at POP1 (r=0.315, p=0.036). CONCLUSION: A noteworthy discovery of this study is the correlation of IL-18BP with SFS24 (r=0.361, p=0.05), proposing that APR and quality of life are associated in MLa patients.

Predictive value of glycoprotein DKK3 for early neurological deterioration after ischemic stroke.

OBJECTIVE: To explore the value of serum Dickkopf-3 (sDKK3) in predicting Early Neurological Deterioration (END) and in-hospital adverse outcomes in acute ischemic stroke (AIS) patients. METHODS: AIS patients (n = 200) were included and assessed by the National Institutes of Health Stroke Rating Scale. Serum Dkk3 levels were assessed by ELISA. END was defined as an increase of ≥ 4 points in NIHSS score within 72h. The biological threshold of sDKK3 level and END occurrence were predicted based on X-tile software. Primary outcomes were END and all-cause death, and the secondary outcome was ICU admission during hospitalization. The logistic regression model and Cox risk regression model were applied to evaluate the relationship between DKK3 level and END incidence, all-cause in-hospital mortality, and in-hospital adverse outcomes (ICU admission). RESULTS: During hospitalization, the incidence of END in patients with AIS was 13.0 %, and the mortality rate within 7 days after END was 11.54 % (3/26). In patients below the serum DKK3 cutoff (93.0 pg/mL), the incidence of END was 43.5 % (20/48). Patients with lower sDKK3 levels were associated with a 1.188-fold increased risk of developing END (OR = 1.188, 95 % CI 1.055‒1.369, p < 0.0001). However, there was no significant association with admission to the ICU. sDKK3 below the threshold (93.0 pg/mL) was a risk factor for death. CONCLUSION: Predictive threshold levels of serum DKK3 based on X-tile software may be a potential predictive biomarker of in-hospital END in patients with AIS, and low levels of DKK3 are independently associated with increased in-hospital mortality.

Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison's disease.

PURPOSE: Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison's disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. METHODS: Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). RESULTS: Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient's age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. CONCLUSION: Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.

Elevated serum levels of leukocyte cell-derived chemotaxin 2 are associated with the prevalence of metabolic syndrome.

AIMS: Inflammation is central to the pathogenesis of metabolic syndrome (MetS). Leukocyte cell-derived chemotaxin 2 (LECT2) is constitutively secreted in response to inflammatory stimuli and oxidative stress contributing to tissue or systemic inflammation. We explored the relationship between LECT2 levels and MetS severity in humans and mice. METHODS: Serum LECT2 levels were measured in 210 participants with MetS and 114 without MetS (non-MetS). LECT2 expression in the liver and adipose tissue was also examined in mice fed a high-fat diet (HFD) and genetically obese (ob/ob) mice. RESULTS: Serum LECT2 levels were significantly higher in MetS participants than in non-MetS participants (7.47[3.36-17.14] vs. 3.74[2.61-5.82], P < 0.001). Particularly, serum LECT2 levels were significantly elevated in participants with hypertension, central obesity, diabetes mellitus (DM), hyperglycaemia, elevated triglyceride (TG) levels, and reduced high-density lipoprotein cholesterol (HDL-C) levels compared to those in participants without these conditions. Pearson's correlation analysis showed that serum LECT2 levels were positively associated with conventional risk factors in all patients. Moreover, LECT2 was positively associated with the number of MetS components (r = 0.355, P < 0.001), indicating that higher serum LECT2 levels reflected MetS severity. Multivariate regression analysis revealed that a one standard deviation increase in LECT2 was associated with an odds ratio of 1.52 (1.01-2.29, P = 0.044) for MetS prevalence after adjusting for age, sex, body mass index, waist circumference, smoking status, white blood cell count, fasting blood glucose, TG, total cholesterol, HDL-C, blood urea nitrogen, and alanine aminotransferase. Receiver operating characteristic curve analysis confirmed the strong predictive ability of serum LECT2 levels for MetS. The optimum serum LECT2 cut-off value was 9.05. The area under the curve was 0.73 (95% confidence interval 0.68-0.78, P < 0.001), with a sensitivity and specificity of 45.71% and 95.61%, respectively. Additionally, LECT2 expression levels were higher at baseline and dramatically enhanced in metabolic organs (e.g. the liver) and adipose tissue in HFD-induced obese mice and ob/ob mice. CONCLUSIONS: Increased LECT2 levels were significantly and independently associated with the presence and severity of MetS, indicating that LECT2 could be used as a novel biomarker and clinical predictor of MetS.

Evaluating STC2 gene RNA in peripheral blood serum of gastric cancer patients.

Cancer is one of the leading causes of death in the world. Invasive microscopic and endoscopic methods are not suitable for routine screening of gastric cancer. Therefore, the need for biomarkers that can detect quickly, efficiently, and with high sensitivity in the early stages of cancer is strongly felt. Stanniocalcin plays a role in regulating calcium and phosphorus in the body. In addition, it plays a role in neuron cell differentiation, angiogenesis, wound healing, fertility and embryo development, and cancer. This study investigated the level of expression of the Stanniocalcin 2 (STC2) gene in the serum of patients with gastric cancer. This case-control study was conducted on the samples of 60 patients with gastric cancer (cases) and 60 healthy individuals (controls). Peripheral blood samples from gastric cancer patients and volunteers as control groups were collected in tubes containing EDTA anticoagulant and were immediately subjected to serum separation. After centrifugation, serum RNA was extracted, and after cDNA synthesis, STC2 gene serum RNA level was measured by the Taq Man method and Real-time PCR using specific primers and probes. Then, the results of serum evaluations and clinicopathological information of patients and control group were collected along with the information obtained from reviewing patients' files and demographic findings, regulatory tables, and related charts. SPSS22 software was used to analyze descriptive data. According to the study results, the high expression of the STC2 gene was 31 cases in the case group and 13 cases in the control group. However, there was a significant relationship between the high expression of the STC2 gene and gastric cancer (p = 0.0001). However, there was no significant relationship between the gender of patients and high expression of the STC2 gene. However, the age of 35% of the patients was more than 65 years, and there was a significant relationship between the age of the patients and the high expression of the STC2 gene (P = 0.028). Although there was no significant relationship between the anatomical location of the cancer and the subtypes of the cancer and the high expression of the STC2 gene, there was a significant relationship between the degree of cancer differentiation and the high expression of STC2 gene (P<0.05). In general, STC2 can be used as a biomarker to determine the border and margins of the tumor. Analysis of STC2 gene expression during surgery can reduce surgical error in tumor removal and increase the success of surgery for tumor removal.

Serum DKK-1 level in ankylosing spondylitis: insights from meta-analysis and Mendelian randomization.

Objective: The purpose of this study was to precisely evaluate the serum Dickkopf-1 (DKK-1) level in patients with ankylosing spondylitis (AS) relative to that in normal controls and to test the causal relationship between DKK-1 and the risk of AS. Methods: Embase, PubMed, Web of Science, WANFANG DATA, VIP, and China National Knowledge Infrastructure (CNKI) were comprehensively searched until July 2022 for pertinent studies. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated by the fixed or random-effect model. In Mendelian randomization (MR) analysis on the causal relationship between serum DKK-1 level and AS risk, the inverse variance weighting method (IVW), MR-Egger regression, weighted median method, and weighted pattern method were applied. Sensitivity analyses, including the horizontal pleiotropy test, heterogeneity test, and leave-one-out test, were also performed. Results: The meta-analysis of 40 studies containing 2,371 AS patients and 1,633 healthy controls showed that there was no significant difference in DKK-1 serum level between AS patients and normal controls (pooled SMD=0.207, 95% CI =-0.418-0.832, P=0.516). The subgroup analysis of the CRP ≤ 10 mg/L group showed that AS patients had higher serum DKK-1 concentration than the healthy controls (SMD=2.267, 95% CI = 0.102-4.432, P=0.040). Similarly, MR analysis also demonstrated no significant association between DKK-1 serum level and AS (IVW OR=0.999, 95% CI = 0.989-1.008, P=0.800). All sensitivity analyses revealed consistent results. Conclusions: There was no significant change in serum DKK-1 concentration between AS patients and healthy controls. In addition, no causal relationship exists between serum DKK-1 levels and AS risk.

Serum Levels of Adropin Improve the Predictability of MELD and Child-Pugh Score in Cirrhosis: Results of Proof-of-Concept Clinical Trial.

Adropin is a peptide that was suggested to have a role in cirrhosis. The present study aimed to determine the ability to use serum adropin levels to improve their prediction accuracy as an adjunct to the current scores. In a single-center, proof-of-concept study, serum adropin levels were determined in thirty-three cirrhotic patients. The data were analyzed in correlation with Child-Pugh and MELD-Na scores, laboratory parameters, and mortality. Adropin levels were higher among cirrhotic patients that died within 180 days (1,325.7 ng/dL vs. 870.3 ng/dL, p = 0.024) and inversely correlated to the time until death (r 2 = 0.74). The correlation of adropin serum levels with mortality was better than MELD or Child-Pough scores (r 2 = 0.32 and 0.38, respectively). Higher adropin levels correlated with creatinine (r 2 = 0.79. p < 0.01). Patients with diabetes mellitus and cardiovascular diseases had elevated adropin levels. Integrating adropin levels with the Child-Pugh and MELD scores improved their correlation with the time of death (correlation coefficient: 0.91 vs. 0.38 and 0.67 vs. 0.32). The data of this feasibility study suggest that combining serum adropin with the Child-Pugh score and MELD-Na score improves the prediction of mortality in cirrhosis and can serve as a measure for assessing kidney dysfunction in these patients.

METFORMIN EFFECTS ON BLOOD LEVELS OF GREMLIN-1 IN POLYCYSTIC OVARIAN WOMEN.

Polycystic ovary syndrome (PCOS), a hormonal disorder affecting millions of women worldwide, characterized by symptoms such as irregular menstrual cycles, weight gain, acne, and excess hair growth. PCOS is linked to higher levels of gremlin-1, a protein involved in ovarian follicle development, which may cause insulin resistance and metabolic abnormalities. The objective is to evaluate the effects of metformin treatment on gremlin-1 levels in patients with PCOS. Sixty patients diagnosed with PCOs based on the Rotterdam criteria were selected as the PCOS group, while 30 healthy women matched for age were selected as the control group. The patients took metformin 850 mg twice daily and provided fasting blood samples before and after treatment. Data was collected through a questionnaire, direct interviewing, ultrasound examination, and laboratory examination, and analyzed using SPSS for Windows 7. The study found that PCOS patients had increased levels of gremlin compared to the control group. Additionally, PCOS patients had increased levels of blood glucose, insulin, and HOMA-IR. After taking metformin, patients showed a significant decrease in gremlin concentration. Treatment with metformin also resulted in a decrease in body mass index, blood glucose, insulin, and HOMA-IR. Metformin decrease gremlin and insulin resistance in patients with polycystic ovary syndrome.

Adropin as a potential protective factor of metabolic complications in obese pregnant women with hyperglycaemia diagnosed in early pregnancy.

Adropin is a hormone which increases insulin sensitivity. It enhances the oxygenation of glucose in the muscles. The 91 obese pregnant women (BMI >30 kg/m2) with gestational diabetes mellitus (GDM) diagnosed in the first half of pregnancy has been recruited to the study group. The control group consisted of 10 age matched and homogeneous pregnant women with BMI <25 kg/m2. Blood samples were collected on visit V1 - between the 28th and 32nd week and on visit V2 - between the 37th and 39th week of gestation. The ELISA test was used to measure the adropin level. The results in the study group and the control group were compared. Blood samples were collected at the same visits. The median concentration of adropin was 442.2 pg/ml on V1 and 453.1 pg/ml on V2. The increase was significant (p<0.05). Results were significantly lower in the control group's patients, i.e. 57.0 pg/ml (p<0.001) on V1 and 107.9 pg/ml on V2 (p<0.001). The higher adropin level on the V1 and V2 visits were related to patients' lower BMI and better metabolic control. The increase in the adropin level in the third trimester may have been involved in the weight gain reduction, whereas better dietary adherence might have had a compensatory effect on increasing insulin resistance. However, the small control group is a limitation of this study.

Circulating levels of adropin and diabetes: a systematic review and meta-analysis of observational studies.

OBJECTIVE: Adropin, a newly identified regulatory protein has garnered attention given its potential role in metabolism regulation, especially glucose metabolism and insulin resistance. However, studies on the association between adropin and type 2 diabetes mellitus (T2DM) are equivocal. The aim of this study is to assess the association between serum adropin levels and T2DM using a systematic review and meta-analysis of observational studies. METHODS: PubMed, Scopus, ISI Web of science, and Google Scholar were searched, up to August 2022, for studies that reported the association between serum levels of adropin in adults with T2DM compared to a control group without diabetes. A random-effect model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Meta-analysis of 15 studies (n = 2813 participants) revealed that the serum adropin concentrations were significantly lower in patients with T2DM compared with the control group (WMD= -0.60 ng/mL, 95% CI: -0.70 to -0.49; I2 = 99.5%). Subgroup analysis also found lower concentration of adropin in patients with T2DM who were otherwise healthy compared to a control group (n = 9; WMD=-0.04 ng/ml, 95% CI= -0.06 to -0.01, p = 0.002; I2 = 96.4). CONCLUSIONS: Our study showed adropin levels are lower in patients with diabetes compared to a control group without diabetes. However, the limitations of observational studies challenge the validity of the results, and further investigations are needed to confirm the veracity of these findings and additionally explore possible mechanisms.

The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease.

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1-KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD.

In Vitro Comparison of Lymphangiogenic Potential of Hypoxia Preconditioned Serum (HPS) and Platelet-Rich Plasma (PRP).

Strategies for therapeutic lymphangiogenesis are gradually directed toward the use of growth factor preparations. In particular, blood-derived growth factor products, including Hypoxia Preconditioned Serum (HPS) and Platelet-rich Plasma (PRP), are both clinically employed for accelerating tissue repair and have received considerable attention in the field of regenerative medicine research. In this study, a comparative analysis of HPS and PRP was conducted to explore their lymphangiogenic potential. We found higher pro-lymphangiogenic growth factor concentrations of VEGF-C, PDGF-BB, and bFGF in HPS in comparison to normal serum (NS) and PRP. The proliferation and migration of lymphatic endothelial cells (LECs) were promoted considerably with both HPS and PRP, but the strongest effect was achieved with HPS-40% dilution. Tube formation of LECs showed the highest number of tubes, branching points, greater tube length, and cell-covered area with HPS-10%. Finally, the effects were double-validated using an ex vivo lymphatic ring assay, in which the highest number of sprouts and the greatest sprout length were achieved with HPS-10%. Our findings demonstrate the superior lymphangiogenic potential of a new generation blood-derived secretome obtained by hypoxic preconditioning of peripheral blood cells-a method that offers a novel alternative to PRP.

Plasma GAS6 predicts mortality risk in acute heart failure patients: insights from the DRAGON-HF trial.

BACKGROUND: Growth arrest-specific 6 (GAS6) is a vitamin K-dependent protein related to inflammation, fibrosis, as well as platelet function. Genetic ablation of GAS6 in mice protects against cardiac hypertrophy and dysfunction. Nonetheless, the association between plasma GAS6 levels and acute heart failure (AHF) patients is still unknown. METHODS: We measured plasma GAS6 concentrations in 1039 patients with AHF who were enrolled in the DRAGON-HF trial (NCT03727828). Mean follow-up of the study was 889 days. The primary endpoint is all-cause death. RESULTS: In total, there were 195 primary endpoints of all-cause death and 135 secondary endpoints of cardiovascular death during the mean follow-up duration of 889 days. The higher levels of GAS6 were associated with higher rates of all-cause and cardiovascular death (P < 0.05). Baseline plasma GAS6 levels were still strongly correlated with clinical outcomes in different models after adjustment for clinical factors and N-terminal pro-brain natriuretic peptide (NT-proBNP, P < 0.05). GAS6 could further distinguish the risks of clinical outcomes based on NT-proBNP measurement. CONCLUSION: Elevated plasma GAS6 levels were associated with an increased risk of all-cause and cardiovascular death in patients with AHF. Trial registration NCT03727828 (DRAGON-HF trial) clinicaltrials.gov.

Apelin-13 and Asprosin in Adolescents with Anorexia Nervosa and Their Association with Psychometric and Metabolic Variables.

Anorexia nervosa (AN) is a widespread, metabo-psychiatric disorder with high relapse rates, comorbidity, and mortality. Many regulatory proteins and neurohormones studied to date play essential roles in the etiopathogenesis of eating disorders and the maintenance of psychopathological symptoms. Nevertheless, the regulatory and pathophysiological mechanisms of AN are still poorly understood. In the presented study, the plasma levels of apelin-13 (APE-13) and asprosin (ASP), as well as carbohydrate metabolism parameters and psychometric parameters, were evaluated in low-weight adolescent female patients with AN (AN1), after partial weight normalization (AN2) and in an age-matched healthy control group (CG) were evaluated. APE-13 levels were higher in the AN1 group than in the post-realimentation and the CG group. APE-13 levels were independent of insulin and glucose levels. Plasma ASP levels increased with increasing body weight in patients with AN, correlating with the severity of eating disorder symptoms in emaciation. The presented data suggest that APE-13 and ASP may be AN's biomarkers-regulation of eating behavior by APE-13 and ASP, the close relationship between them and emotional behavior, and changes in neurohormone levels in patients with eating and affective disorders seem to support these hypotheses. Moreover, their plasma levels seem to be related to the severity of psychopathological symptoms of eating disorders.

The effectiveness of serum S100B, TRAIL, and adropin levels in predicting clinical outcome, final infarct core, and stroke subtypes of acute ischemic stroke patients. / Eficacia de los niveles séricos de S100B, TRAIL y adropina para predecir el resultado clínico, el núcleo del infarto final y los subtipos de ataque cerebrovascular de los pacientes con accidente cerebrovascular isquémico agudo

INTRODUCTION: More than half of all worldwide deaths and disabilities were caused by stroke. Large artery atherosclerosis is identified as a high etiological risk factor because it accounts for 20% of ischemic stroke. OBJECTIVES: To identify the significance of TRAIL and adropin release and the relative changes related to S100B levels, as well as the relationship between these biomarkers and the final infarct core, the clinical outcome, and the presence of large artery atherosclerosis in acute stroke patients. MATERIALS AND METHODS: Over a one-year period, demographic, clinical, and neuroimaging findings of 90 consecutive patients with acute ischemic stroke were evaluated. RESULTS: The mean age of participants was 69.28 ± 10 and 39 patients were female. The increased level of S100B and the decreased levels of sTRAIL with adropin were significantly associated with moderate to severe neurologic presentation (p=0.0001, p=0.002, p=0.002, respectively). On the control CT, a large infarct core was significantly associated with decreased serum levels of sTRAIL and adropin (p=0.001 and p=0.000, respectively); however, the levels of S100B were not significantly associated with good ASPECTS score (p=0.684). Disability and an unfavorable outcome were significantly related to the decreased level of sTRAIL and adropin (p=0.001 and p=0.000 for THRIVE score>5, respectively). Decreased sTRAIL and adropin levels and an increased S100B level were correlated with the presence of large artery atherosclerotic etiologic factors (p=0.000, p=0.000, p=0.036, respectively). CONCLUSION: TRAIL and adropin serum levels were associated with poor clinical outcomes and greater infarcted area in acute ischemic stroke patients.

Introducción. Más de la mitad de todas las muertes y discapacidades en todo el mundo fueron causadas por accidentes cerebrovasculares. La aterosclerosis de las grandes arterias se identifica como un factor de alto riesgo etiológico debido a que representa el 20 % de los accidentes cerebrovasculares isquémicos. Objetivo. Determinar la importancia de la liberación de TRAIL y adropina y los cambios relativos relacionados con los niveles de S100B, así como la relación entre estos biomarcadores y el núcleo final del infarto, el resultado clínico y la presencia de aterosclerosis de arterias grandes en pacientes con accidente cerebrovascular agudo. Materiales y métodos. Durante un año, se evaluaron los hallazgos demográficos, clínicos y de neuroimágenes de 90 pacientes con accidente cerebrovascular isquémico agudo. Resultados. La edad media de los pacientes fue de 69,28 ± 10 y 39 eran mujeres. El aumento del nivel de S100B y la disminución de los niveles de sTRAIL y adropina se asociaron significativamente con una presentación neurológica moderada a grave en los pacientes (p=0,0001, p=0,002 y p=0,002, respectivamente). En la TC de control, un gran núcleo de infarto se asoció significativamente con una disminución del nivel sérico de sTRAIL y adropina (p=0,001 y p=0,000, respectivamente); sin embargo, los niveles de S100B no se asociaron significativamente con una buena puntuación en el ASPECT (p=0,684). La discapacidad y el resultado desfavorable se relacionaron significativamente con la disminución de los niveles de sTRAIL y adropina (p=0,001 y p=0,000 para una puntuación >5 en el THRIVE, respectivamente). La disminución de los niveles de sTRAIL y adropina y el aumento del nivel de S100B, se correlacionaron con la presencia de un factor etiológico aterosclerótico de arterias grandes entre la población de estudio (p=0,000, p=0,000 y p=0,036, respectivamente). Conclusiones. Los niveles séricos de TRAIL y adropina se asociaron con un resultado clínico deficiente y una mayor área infartada en pacientes con ataque cerebrovascular isquémico agudo.