Immunomodulatory Potential of Escitalopram on C-C Motif Chemokine Ligand 5 and Fibroblast Growth Factor 2 in Patients With Generalised Anxiety Disorder.

Multiple myeloma is the plasma cell malignancy in which bone involvement is common. The Fibroblast growth factor-23 (FGF-23)/Klotho pathway plays a major role in mineral metabolism that FGF-23 is mineralization inhibitory. Klotho also has anti-apoptotic and anti-tumor effects by acting as a tumor suppressor gene. There is a negative correlation between serum FGF-23 and serum soluble Klotho (sKL) levels. As such, there can be considerable interest in investigating sKL and FGF-23 as a biomarker in patients with MM. We used an enzyme-linked immunosorbent assay to measure serum FGF-23 and sKL levels in 55 newly diagnosed MM patients and 23 healthy controls. We determined significantly high serum FGF-23 and low serum sKL levels in MM patients when compared to healthy controls. Serum sKL levels correlated negatively with a p53 positive mutation status, with high ISS, elevated lactate dehydrogenase, C-reactive protein, Beta-2 microglobulin levels. Serum FGF-23 levels are associated negatively with serum phosphorus and positively only light chains and p53 mutation. Patients with high serum FGF-23 levels had significantly shorter median overall survival than those with low serum FGF-23 levels (p = 0.008). Additionally, low sKL levels were related to decreased overall survival, but they didn't reach statistically significant (p = 0.072). There is a significant correlation between low serum sKL, high FGF-23 levels, and known prognostic factors in MM patients. We conclude that low sKL and high FGF-23 levels are a probable prognostic biomarker for poor MM patient outcomes.

To explore the features of events-related potentials (ERP) component N400 in generalized anxiety disorder (GAD) versus obsessive compulsive disorder (OCD) patients and understand the cognitive pattern and processing characteristic for Chinese characters. ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP apparatus. And 41 GAD patients, 69 OCD patients and 58 normal controls (NC) were tested by the Chinese idioms ending with matching (congruent) or mismatching (incongruent) words. (1) Latencies: Significant differences were found of N400 latencies in ending words with the same pronunciation but different forms and meanings (NC: (377 ± 40) ms, OCD: (395 ± 43) ms, GAD: (396 ± 43) ms, congruent; NC: (415 ± 32) ms, OCD: (429 ± 35) ms, GAD: (430 ± 36) ms, incongruent), ending words with the same meaning but different pronunciations and forms (NC: (411 ± 32) ms, OCD: (424 ± 40) ms, GAD: (433 ± 39) ms, incongruent), ending words with different pronunciations, forms and meanings (NC: (399 ± 47) ms, OCD: (427 ± 53) ms, GAD: (434 ± 42) ms, congruent; NC: (442 ± 36) ms, OCD: (465 ± 35) ms, GAD: (474 ± 35) ms, incongruent) (P < 0.05 - 0.01). Compared with NC, the N400 latencies were prolonged in GAD and OCD patients. Compared with OCD patients, the GAD patients also showed prolonged N400 latencies in ending words with different pronunciations, forms and meanings (incongruent situation). (2) Significant differences were found of N400 amplitudes in ending words with the same pronunciation but different forms and meanings (NC: (9 ± 5) µV, OCD: (6 ± 5) µV, GAD: (6 ± 5) µV, congruent; NC: (11 ± 6) µV, OCD: (5 ± 4) µV, GAD: (6 ± 4) µV, incongruent), ending words with similar forms but different pronunciations and meanings (NC: (9 ± 5) µV, OCD: (5 ± 4) µV, GAD: (7 ± 5) µV, congruent; NC: (14 ± 6) µV, OCD: (6 ± 5) µV, GAD: (9 ± 7) µV, incongruent), ending words with different pronunciations, forms and meanings (NC: (9 ± 5) µV, OCD: (5 ± 4) µV, GAD: (5 ± 3) µV, congruent; NC: (14 ± 6) µV, OCD: (9 ± 7) µV, GAD: (9 ± 7) µV, incongruent) (P < 0.05 - 0.01). Compared with NC, N400 amplitudes decreased in GAD and OCD patients respectively. Compared with OCD patients, the GAD patients also showed elevated N400 amplitudes in ending words with similar forms but different pronunciations and meanings (congruent). The cognitive and emotional problems in GAD and OCD may be measured by N400 elicited by Chinese idioms. Notable N400 priming effects can be found in Chinese idioms.

There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2 concentrations were compared among SSc, disease control (systemic lupus erythematosus (SLE)), and healthy control groups. We also examined the association of serum levels of PTX3 and FGF2 with disease manifestations. Serum PTX3 levels were similarly distributed among SSc (n=93) and healthy groups (n=66) (p=1.00) while PTX3 levels were higher in SLE controls (n=86) compared to both SSc and healthy groups. PTX3 levels were higher in limited SSc cases compared to diffuse cases (p=0.016). Median PTX3 levels in SSc cases with lung involvement were lower compared to cases with no lung involvement (p=0.006). Patients with SSc had significantly lower serum levels of FGF2 compared to SLE and healthy groups. Serum FGF2 concentration was undetectable in 61.3% of cases with SSc while 30.2% of SLE and only 4.5% of healthy cases had undetectable FGF2 levels (p<0.01). Diffuse and limited SSc cases, as well as cases with and without lung involvement, had similar rates of undetectable serum FGF2 levels (p=0.15 and p=0.59, respectively). FGF2 levels were mostly undetectably low in patients with SSc, and serum PTX3 was lower in diffuse SSc and in cases with lung involvement compared to limited SSc and cases with no lung involvement, respectively, in our cohort.

Shared and distinctive changes of the white matter integrity in generalized anxiety disorder with or without depressive disorder.

Objectives:This study aims to compare patients with major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD), whom we have frequently seen in our hospital practice during the pandemic, with healthy controls (HC) in terms of coronavirus anxiety levels and coping strategies.Methods:In this study, the Sociodemographic Data Form, Coronavirus Anxiety Scale (CAS), Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Coping Orientation to Problems Experienced (COPE) scale were applied to the participants. 30 MDD patients, 32 GAD patients, 31 PD patients and 38 HCs, totaling 131 participants, constituted the sample of the study.Results:Evaluation of the CAS scores of the participants revealed that HC scored 3.306 (p=0.002) points lower than GAD patients and 3.014 (p=0.005) points lower than PD patients, while HC and major depression patients were not statistically different in terms of CAS scores (p=0.880). In the comparison of coping strategies, HC scored 3.151 (p<0.001) points higher than MDD patients and 2.059 (p=0.004) points higher than GAD patients in terms of “active coping.” In terms of “planning,” HC scored 2.726 (p<0.001) points higher than MDD patients, 2.589 (p=0.001) points higher than GAD patients, and 2.171 (p=0.006) points higher than PD patients.Conclusion:This study found higher coronavirus anxiety levels in GAD and PD patients but no difference in MDD patients compared to HC during the COVID-19 pandemic, which may indicate that MDD patients can COPE better with coronavirus anxiety. Determining the coping strategies that individuals use to COPE with coronavirus anxiety during the COVID-19 pandemic may help mental health professionals to control disease-related stressors and contribute to the treatment process.

Plasminogen and plasmin can bind to human T cells and generate truncated CCL21 that increases dendritic cell chemotactic responses

BackgroundHigh serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD.MethodsCKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods.ResultsSerum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P<0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P<0.01).ConclusionsHigher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.

Porcine embryos are used for a variety of applications. However, the maturation rate in vitro remains low, and novel in vitro maturation (IVM) techniques that facilitate the collection of mature oocytes are necessary. C-C motif chemokine ligand 2 (CCL2) is a key periovulatory chemokine present in cumulus-oocyte complexes (COCs). We aimed to examine the effects of CCL2 supplementation during IVM on oocyte maturation and embryonic development. The CCL2 concentration was significantly higher in porcine follicular fluid (pFF) derived from follicles >8 mm in size than in pFF derived from smaller follicles. There was a significant increase in CCL2 mRNA levels in all follicular cells after IVM compared with that before IVM. We analyzed the localization of CCL2 and its receptor, the CCL2 receptor, in follicular cells. During IVM, different concentrations of CCL2 were added to COCs cultured in a maturation medium. After IVM, the group treated with 100 ng/mL CCL2 showed significantly higher metaphase II rates than the control group. All CCL2-treatment groups showed a significant increase in intracellular glutathione levels and a significant decrease in reactive oxygen species levels, compared to the control. In CCs treated with 100 ng/mL CCL2, the mRNA levels of BAX, CASP3, and NPR2 were significantly decreased. Furthermore, the mRNA levels of SOD1, SOD2, and CD44 were significantly increased. In oocytes treated with 10 ng/mL CCL2, mRNA levels of BAX and CASP3 were significantly decreased, whereas, NRF2 and NPM2 were significantly increased. ERK1 exhibited significantly increased mRNA expression in both CCs and oocytes treated with 10 ng/mL CCL2. The protein expression ratio of phosphorylated ERK1/2 to total ERK1/2 was significantly increased in CCs treated with 10 ng/mL CCL2. After parthenogenetic activation, cleavage rates were significantly improved in the 100 ng/mL CCL2 treatment group, and blastocyst formation rates were significantly enhanced in the 10 ng/mL CCL2 treatment group. Overall, our results suggest that IVM medium along with CCL2 improves porcine oocyte maturation and the development of parthenogenetically-activated embryos.

Sickness behavior defines the endocrine, autonomic, behavioral, and metabolic responses associated with infection. While inflammatory responses were suggested to be instrumental in the loss of appetite and body weight, the molecular underpinning remains unknown. Here, we show that systemic or central lipopolysaccharide (LPS) injection results in specific hypothalamic changes characterized by a precocious increase in the chemokine ligand 2 (CCL2) followed by an increase in pro-inflammatory cytokines and a decrease in the orexigenic neuropeptide melanin-concentrating hormone (MCH). We therefore hypothesized that CCL2 could be the central relay for the loss in body weight induced by the inflammatory signal LPS. We find that central delivery of CCL2 promotes neuroinflammation and the decrease in MCH and body weight. MCH neurons express CCL2 receptor and respond to CCL2 by decreasing both electrical activity and MCH release. Pharmacological or genetic inhibition of CCL2 signaling opposes the response to LPS at both molecular and physiologic levels. We conclude that CCL2 signaling onto MCH neurons represents a core mechanism that relays peripheral inflammation to sickness behavior.

Cortical activation patterns in generalized anxiety and major depressive disorders measured by multi-channel near-infrared spectroscopy.

Symptomatic diagnosis combined with unclear pathological mechanism and diverse etiology may increase misdiagnosis risk for generalized anxiety disorder (GAD) in the clinical setting. This study aimed to confirm the diagnostic value of aberrantly expressed long non-coding RNAs (lncRNAs) for GAD. Eighty sex- and age-matched patients with GAD and major depressive disorder (MDD) and healthy controls (HCs) were enrolled using a convenient sampling method. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify lncRNA expression levels in all participants, and a receiver operating characteristic (ROC) curve was used to test the accuracy of aberrantly expressed lncRNAs in differentiating health conditions. ΔCt values of ENST00000505825, NONHSAG017299, NONHSAT078768, NONHSAT029028, NONHSAT101077, NONHSAT031726, TCONS_l2_00010607 in GAD patients were less than in HCs (P<0.05 or 0.01). The total severity score of HAMA-14 and somatic anxiety scores were negatively correlated with ΔCt values of ENST00000505825, NONHSAG017299, NONHSAT078768, NONHSAT029028, NONHSAT101077, NONHSAT031726, ENST00000505825, TCONS_l2_00010607, and NONHSAT131696, and psychic anxiety scores were negatively associated with the ΔCt value of ENST00000505825 (P<0.05 or 0.01). The AUC of the combined ROC curve between patients with GAD and healthy people was 0.810, with sensitivity and specificity of 0.825 and 0.762, respectively (P<0.05 or 0.01). The AUC of the combined ROC curve between patients with GAD and MDD patients was 0.938, with sensitivity and specificity of 0.850 and 0.900, respectively (P<0.05 or 0.01). ENST00000505825, NONHSAG017299, NONHSAT078768, NONHSAT029028, NONHSAT101077, NONHSAT031726, TCONS_l2_00010607, which may serve as biomarkers for the GAD diagnosis and differentiation between GAD and MDD, can improve the diagnostic accuracy and avoid misdiagnosis to a certain extent. It is also beneficial for personalized treatment of GAD.

There is a remarkable interaction among the factors that increase fibroblast growth factor 23 (FGF23) transcription in the osteocyte and osteoblast, where they are individually and collectively essential for the fine tuning of FGF23 expression and secretion. Serum levels of the three hormones, PTH,

Muscle mass decreases with aging, while the C-C motif chemokine ligand 2 (CCL2) increases with aging; in this context, CCL2 can be considered a potential aging-promoting factor. Thus, CCL2 knockout mice are expected to exhibit anti-aging effects including protection against loss of muscle mass. However, instead, muscle amount and recovery of damaged muscles are decreased in CCL2 knockout mice. Therefore, we hypothesized that increasing CCL2 in the elderly might be related to compensation for loss of muscle mass. To confirm the relationship between muscle and CCL2, we sought to establish the role of CCL2 in C2C12 cells and Human Skeletal Muscle Myoblast (HSMM) cells. The myotube (MT) fusion index increased with CCL2 compared to 5day CCL2 vehicle only (27.0 % increase, P<0.05) in immunocytochemistry staining (ICC) data. CCL2 also restored MTs atrophy caused by dexamethasone (21.8 % increase, P<0.0001). p-mTOR/mTOR and p-AKT/total AKT increased with CCL2 compared to CCL2 vehicle only (18.3 and 30.5% increase respectively, P<0.05) and decreased with CCR2-siRNA compared to CCL2 (38.9 % (P<0.05) and 56.7% (P<0.005) reduction respectively). In conclusion, CCL2 positively affects myogenesis by CCR2 via AKT-mTOR signaling pathways. CCL2 might have potential as a therapeutic target for low muscle mass and muscle recovery.

BackgroundAxial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects axial skeleton. The disease is characterised by new bone formation; it usually starts with the bony fusion of sacroiliac...

This study aimed to explore the role of the default mode network (DMN) and salience network (SN) in the assessment of pathophysiology of generalized anxiety disorder (GAD) through analyzing the characteristics of internal function connectivity (FC) and to investigate the relationship of FC with Hamilton anxiety (HAMA) scale scores in untreated GAD patients during a resting-state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI and HAMA scale scoring were performed in 51 GAD patients (31 GAD patients with liver stagnation transforming into fire type and 20 GAD patients with stagnation of liver-Qi syndrome type) and 20 healthy controls. Spearman correlation analysis was performed to assess the association between HAMA scores and abnormal brain FC. Compared with healthy controls, the FC of the right medial prefrontal gyrus of the DMN and the right superior temporal gyrus of the SN increased significantly in the GAD patients (P < 0.001). However, the FC of the left middle frontal gyrus and bilateral medial superior frontal gyrus of the SN reduced significantly in the GAD patients with stagnation of liver-Qi syndrome type as compared with healthy controls and GAD patients with liver stagnation transforming into fire type (P < 0.001). There was no relationship between abnormal brain FC and HAMA scores. In conclusion, the FC of the DMN and SN may be abnormal in the GAD patients at the resting state. The aberrant FC of some crucial brain regions of these networks may contribute to the pathophysiology of GAD.