Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging.

BACKGROUND: Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. RESULTS: Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. CONCLUSIONS: Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.

Soluble PILRα: A novel plasma biomarker for atrial fibrillation progression and recurrence after catheter ablation.

BACKGROUND: We aimed to identify plasma biomarkers of atrial fibrillation (AF) progression and recurrence after catheter ablation. METHODS: Using AF gene profiling data from GEO database, a weighted gene co-expression network analysis (WGCNA) was conducted to determine the most significant module and hub genes associated with AF. Subsequently, 318 consecutively admitted patients who had undergone radiofrequency catheter ablation were enrolled in this study. RESULTS: WGCNA results revealed that paired immunoglobulin-like type 2 receptor alpha (PILRA) was the only black module gene highly correlated with clinical traits. Plasma soluble PILRα (sPILRα) levels were elevated in patients with AF and significantly elevated in patients with persistent versus paroxysmal AF (4.64 ± 2.74 vs. 3.04 ± 1.56 ng/mL, p < 0.001). Elevated sPILRα level was an independent risk factor for AF progression even after adjusting for traditional factors (adjusted odds ratio: 3.06, 95 % confidence interval [CI]: 1.88-5.27, p < 0.001) and AF recurrence after catheter ablation in patients with persistent AF (adjusted hazards ratio: 4.41, 95 % CI: 1.22-15.92, p = 0.023). CONCLUSIONS: WGCNA screening of GEO microarray gene profiling data showed PILRA expression levels to be correlated with AF progression and recurrence after catheter ablation in patients with persistent AF.

The Role of OH Cards in Psychological Interventions for Children With Fractures.

Context: Fractures are traumatic events, with psychological effects that can have a negative impact on children hospitalized with fractures. They can seriously affect children's physical rehabilitation and quality of life and even produce psychological disorders The OH card is a metaphorical card that allows access to an individual's inner world and can have a positive effect in psychotherapy. Objective: The study intended to investigate the use of OH Cards during psychological interventions with children with fractures and to provide a methodological reference for the use of OH Cards in therapy. Design: The research team performed a randomized controlled study. Setting: The study took place in the Department of Trauma Surgery at Children's Hospital of Hebei Province in Shijiazhuang, China. Participants: Participants were 74 children with fractures who had been admitted to the hospital between September 2020 and November 2021. Intervention: The research team randomly divided participants into two groups using a random number table: (1) 37 in the intervention group, who received a conventional nursing intervention and also an OH-card intervention, and (2) 37 in the control group, who received conventional nursing interventions only. Outcome Measures: At baseline and postintervention, the research team: (1) measured the participants' posttraumatic growth scores, using the children's version of the Post-Traumatic Growth Inventory (PTGI); (2) assessed their coping styles, using the Medical Coping Modes Questionnaire (MCMQ); (3) determined the existence of any stress disorders, using the Child Stress Disorder Checklist (CSDC); (4) evaluated their mental statuses using the Depression Self-Rating Scale (DSRSC) and the Screen for Child Anxiety-related Emotional Disorders (SCARED); and (5) measured participants' Fracture Knowledge Questionnaire scores. Results: At baseline, no significant differences existed between the groups for any outcome measure at baseline. Postintervention, the intervention group's scores: (1) on the PTGI, were significantly higher for mental change, appreciate life, individual force, new possibilities and personal relation than those of the control group; (2) on the MCMQ, were significantly higher for facing and significantly lower for avoidance and yield than those of the control group; (3) on the CSDC, were significantly lower for trauma incidents and acute response than the control group did; (4) on the DSRSC were significantly lower and on SCARED were significantly higher than those of the control group; and (5) on the Fracture Knowledge Questionnaire were significantly higher than those of the control group. Conclusions: OH Cards can increase the posttraumatic growth scores of children with fractures, improve their coping styles, reduce stress disorders, decrease depression and improve their psychological state, increase their knowledge about fractures, and promote their recovery.

SerpinG1: A Novel Biomarker Associated With Poor Coronary Collateral in Patients With Stable Coronary Disease and Chronic Total Occlusion.

Background This study aimed to explore predictive biomarkers of coronary collateralization in patients with chronic total occlusion. Methods and Results By using a microarray expression profiling program downloaded from the Gene Expression Omnibus database, weighted gene coexpression network analysis was constructed to analyze the relationship between potential modules and coronary collateralization and screen out the hub genes. Then, the hub gene was identified and validated in an independent cohort of patients (including 299 patients with good arteriogenic responders and 223 patients with poor arteriogenic responders). Weighted gene coexpression network analysis showed that SERPING1 in the light-cyan module was the only gene that was highly correlated with both the gene module and the clinical traits. Serum levels of serpinG1 were significantly higher in patients with bad arteriogenic responders than in patients with good arteriogenic responders (472.53±197.16 versus 314.80±208.92 µg/mL; P<0.001) and were negatively associated with the Rentrop score (Spearman r=-0.50; P<0.001). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.77 (95% CI, 0.72-0.81; P<0.001) for serum serpinG1 in prediction of bad arteriogenic responders. After adjusting for traditional cardiovascular risk factors, serum serpinG1 levels (per SD) remained an independent risk factor for bad arteriogenic responders (odds ratio, 2.20 [95% CI, 1.76-2.74]; P<0.001). Conclusions Our findings illustrate that SERPING1 screened by weighted gene coexpression network analysis was associated with poor collateralization in patients with chronic total occlusion.

Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients.

BACKGROUND: The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. OBJECTIVES: This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. RESULTS: Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P < 0.001). We categorized these patients with diabetes into MPO level or activity tertile subgroups. Significant differences in the plaque progression ratio and prominent changes in the minimal lumen diameter, stenosis diameter and coronary artery stenosis score were observed across the tertile subgroups of MPO levels and activities (all P < 0.01). Moreover, serum MPO levels and activities correlated significantly with these indices of coronary artery disease severity after adjustment for other risk factors. Multivariable regression analyses revealed that serum MPO levels and activities remained independently associated with plaque progression, in addition to smoking, hypertension and CRP levels (all P < 0.05). CONCLUSIONS: Serum MPO levels and activities are significantly associated with coronary atherosclerotic plaque progression in patients with type 2 diabetes.

Serum apolipoprotein A-IV levels are associated with flow-mediated dilation in patients with type 2 diabetes mellitus.

BACKGROUND: Endothelial dysfunction is common in diabetes. Apolipoprotein (apo) A-IV functions to antagonize inflammation and oxidative stress. The present study aimed to investigate the relationship between flow-mediated dilation (FMD) and serum apoA-IV level in type 2 diabetes mellitus (T2DM) patients.  METHODS: A total of 84 T2DM patients with chest discomfort were enrolled in this study. Their baseline characteristics and clinical parameters were documented. Endothelial function of the participants was evaluated by examining FMD of brachial artery. The severity of coronary atherosclerosis was determined by quantitative coronary angiography. Serum apoA-IV levels were measured by ELISA. RESULTS: These diabetic patients were dichotomized into low FMD (n = 42) and high FMD (n = 42) groups. Serum apoA-IV levels were significantly higher in high FMD group than in low FMD group (29.96 ± 13.17 vs 17.69 ± 9.16 mg/dL, P < 0.001). Moreover, the patients were also categorized into three apoA-IV tertile groups. FMD was significantly different across three apoA-IV tertiles (P < 0.001). Serum apoA-IV levels were positively correlated to FMD (r = 0.469, P < 0.001). Logistic regression analysis was performed to determine risk factors for low FMD. apoA-IV levels together with the risk factor hsCRP remained significantly to be independent determinants of low FMD (P < 0.01). Linear regression analysis was performed, and apoA-IV levels together with total-to-HDL cholesterol ratio were independently correlated with FMD (P < 0.01). CONCLUSIONS: Serum apoA-IV levels are associated with FMD, suggesting that apoA-IV protects endothelial function in patients with T2DM.

High serum levels of N-epsilon-carboxymethyllysine are associated with poor coronary collateralization in type 2 diabetic patients with chronic total occlusion of coronary artery.

BACKGROUND: The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. METHODS: This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. RESULTS: 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors. CONCLUSIONS: This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

Association of Circulating IgE and CML Levels with In-Stent Restenosis in Type 2 Diabetic Patients with Stable Coronary Artery Disease.

Background: We investigated whether serum levels of immunoglobin (Ig) E and Nε-carboxymethyl-lysine (CML) are related to in-stent restenosis (ISR) in patients with stable coronary artery disease and type 2 diabetes mellitus (T2DM). Methods: Serum levels of IgE and CML were measured in 196 ISR patients and 220 non-ISR patients with stable angina and T2DM who received angiographic follow-up 12 months after percutaneous coronary intervention (PCI) with third-generation drug-eluting stent (DES) implantation for de novo lesions. Multivariate logistic regression analysis was performed to assess the association between IgE or CML and ISR. Results: Both IgE and CML levels were higher in patients with ISR compared with non-ISR patients (IgE: 187.10 (63.75−489.65) vs. 80.25 (30.65−202.50), p < 0.001; CML: 203.26 (164.50−266.84) vs. 174.26 (130.85−215.56), p < 0.001). The rate of ISR increased stepwise with increasing tertiles of IgE and CML levels (p for all trends < 0.001), and IgE correlated significantly with CML. After adjusting for potential confounders, IgE and CML levels remained independently associated with ISR. Moreover, IgE and CML levels improved the predictive capability of traditional risk factors for ISR, and there existed an interaction between IgE and CML in relation to ISR (p for interaction < 0.01). Conclusion: Elevated circulating IgE and CML levels confer an increased risk for ISR after DES-based PCI in type 2 diabetic patients with stable coronary artery disease.

Copan Walk Away Specimen Processor (WASP) Automated System for Pathogen Detection in Female Reproductive Tract Specimens.

Objective: Automation is increasingly being applied in clinical laboratories; however, preanalytical processing for microbiology tests and screening is still largely performed using manual methods owing to the complex procedures involved. To promote automation of clinical microbiology laboratories, it is important to assess the performance of automated systems for different specimen types separately. Therefore, the aim of this study was to explore the potential clinical application of the Copan Walk Away Specimen Processor (WASP) automated preanalytical microbiology processing system in the detection of pathogens in female reproductive tract specimens and its feasibility in optimizing diagnostic procedures. Methods: Female reproductive tract specimens collected from pregnant women at their first obstetric check-up were inoculated into culture media using the Copan WASP automated specimen processing system and were also cultured using a conventional manual inoculation method. After 48 h of culture, the growth of colonies was observed, and the types of bacteria, number of colonies, and efficiency in isolating single colonies were compared between the automated and manual groups. The specimens collected from the WASP system using the Copan-ESwab sample collection tubes were further analyzed for the presence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasmaurealyticum (UU) via fluorescence quantitative polymerase chain reaction (qPCR) and an immunochromatographic assay to investigate the feasibility of this method in optimizing detection of these common pathogens of the female reproductive tract. Results: Compared with the manual culture method, the Copan WASP microbiology automation system detected fewer bacterial types (P<0.001) and bacterial colonies (P<0.001) but had a higher detection rate of single colonies (P<0.001). There was no significant difference in the detection rates of common pathogens encountered in clinical obstetrics and gynecology, including group B Streptococcus (GBS) (P=0.575) and Candida (P=0.917), between the two methods. Specimens collected in the Copan-ESwab tubes could be used for screening of GBS and CT via fluorescence-based qPCR but not with immunochromatography. However, UU and NG were not detected in any sample with either method; thus, further validation is required to determine the feasibility of the Copan system for screening these pathogens. Conclusion: The Copan WASP microbiology automation system could facilitate the optimization of diagnostic procedures for detecting common pathogens of the female reproductive system, thereby reducing associated costs.

Downregulation of Ribosomal Contents and Kinase Activities Is Associated with the Inhibitive Effect on the Growth of Group B Streptococcus Induced by Placental Extracellular Vesicles.

BACKGROUND: Like many other cell types, the human placenta produces large amounts of extracellular vesicles (EVs). Increasing evidence has shown that placental EVs contribute to the regulation of maternal immune and vascular systems during pregnancy via the transfer of their cargos. In this study, we investigated the effect of placental EVs on the growth of opportunistic pathogens that commonly colonise the female reproductive tract. METHODS: Gram-positive bacterium Group B Streptococcus (GBS) and Gram-negative bacterium Escherichia coli (E. coli) were treated with placental EVs that were collected from placental explant cultures, and the growth, susceptibility, and resistance to antibiotics of the bacteria were measured. In addition, comparative proteomics analysis was also performed for the GBS with or without exposure to placental EVs. RESULTS: When treated with placental micro-EVs or nano-EVs, the GBS growth curve entered the stationary phase earlier, compared to untreated GBS. Treatment with placental EVs also inhibited the growth of GBS on solid medium, compared to untreated GBS. However, these biological activities were not seen in E. coli. This attenuative effect required interaction of placental EVs with GBS but not phagocytosis. In addition, the susceptibility or resistance to antibiotics of GBS or E. coli was not directly affected by treatment with placental EVs. The proteomic and Western blotting analysis of GBS that had been treated with placental EVs suggested that the downregulation of cellular components and proteins associated with phosphorylation and cell energy in GBS may contribute to these attenuative effects. CONCLUSION: We demonstrated the attenuative effect of the growth of GBS treated with placental EVs. Downregulation of cellular components and proteins associated with phosphorylation and cell energy may contribute to the physiological changes in GBS treated with placental EVs.

Soluble ST2 levels for predicting the presence and severity of metabolic syndrome.

To explore the relationship between soluble ST2 (sST2) and metabolic syndrome (MetS) and determine whether sST2 levels can predict the presence and severity of MetS. We evaluated 550 consecutive subjects (58.91 ± 9.69 years, 50% male) with or without MetS from the Department of Vascular & Cardiology, Shanghai Jiao Tong University-Affiliated Ruijin Hospital. Serum sST2 concentrations were measured. The participants were divided into three groups according to the sST2 tertiles. Univariate and multivariable logistic regression models were used to evaluate the association between serum sST2 concentrations and the presence of MetS. Serum sST2 concentrations were significantly higher in the MetS group than in those in the no MetS group (14.80 ± 7.01 vs 11.58 ± 6.41 ng/mL, P < 0.01). Subjects with more MetS components showed higher levels of sST2. sST2 was associated with the occurrence of MetS after multivariable adjustment as a continuous log-transformed variable (per 1 SD, odds ratio (OR): 1.42, 95% CI: 1.13-1.80, P < 0.01). Subgroup analysis showed that individuals with MetS have significantly higher levels of sST2 than those without MetS regardless of sex and age. High serum sST2 levels were significantly and independently associated with the presence and severity of MetS. Thus, sST2 levels may be a novel biomarker and clinical predictor of MetS.

Anti-migraine effect of wine-processed Radix scutellariae: Pharmacodynamic verification in nitroglycerin-induced rats and correlation study between compounds dissolution and the fractal dimension.

ETHNOPHARMACOLOGICAL RELEVANCE: Wine-processed Radix scutellariae (RS) is the processed product of RS, which is the dried root of Scutellaria baicalensis Georgi. It is recorded in Chinese traditional formula that wine-processed RS has the effect of anti-migraine, while the effect has not been confirmed and the possible mechanism remains unclear. AIM OF THE STUDY: To verify the anti-migraine effect of wine-processed RS in nitroglycerin (NTG)-induced rats and explore the correlation between compounds dissolution and the pore structure based on fractal theory. MATERIALS AND METHODS: In the validation of pharmacodynamics, the effects of wine-processed RS on migraines were firstly evaluated by observing the number of head-scratching of rats, then investigated by determining the levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP) and the expression of c-Fos in the brain of NTG-induced rat models using ELISA and immunohistochemical assessments. In the correlation study, the stir-frying time of RS was set to 5 min, 10 min and 15 min. The scanning electron microscope (SEM) and mercury intrusion method were used to explore the pore structure and main parameters of the pore structure including pore size distribution, pore volume, porosity, surface area and fractal dimension. The compounds dissolution of total flavonoids and five major components containing baicalein, baicalin, scutellarin, wogonin and wogonoside was determined by UV-Vis spectrophotometry and HPLC separately. RESULTS: The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p < 0.01) and markedly decrease the levels of NO (p < 0.01), CGRP (p < 0.05) and the expression of c-Fos (p < 0.01) compared with model group. The data indicated that wine-processing would affect the dissolution of compounds by changing the pore structure of RS. The order of positive correlation between pore structure parameters and compounds' dissolution was total surface area > fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r < 0). Compared with the other sample groups (p < 0.05), the wine-processed RS stir-fried for 10 min had a pore structure which was more favorable for compounds dissolution. CONCLUSIONS: Wine-processing could strengthen the anti-migraine effect of RS by changing the pore structure of RS, which is linked to the dissolution of compounds. The RS stir-fried for 10 min may be more effective in treating migraine.

Effect of liquiritin on neuroendocrine-immune network in menopausal rat model.

PURPOSE: The aim of the study was to investigate the effect of liquiritin on neuroendocrine-immune network in menopausal rat model. METHODS: Liquiritin groups were respectively given liquiritin suspension at the dose of 80, 40, and 20 mg/kg, once a day for continuous 30 days after the removal of bilateral ovaries to induce the menopausal rat model. Behavioral experiments were conducted and the organs were weighed for the viscera index. The content of estradiol (E2 ) and follicle-stimulating hormone (FSH) in the serum and 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hypothalamus were assayed by enzyme linked immunosorbent assay kits. Morphological changes of uterus and adrenal gland were observed by hematoxylin-eosin (HE) staining and estrogen receptor (ER) expression of uterus and spleen were determined by immunohistochemical staining. RESULTS: For the nervous system, liquiritin relieved menopausal depression and up-regulated the levels of 5-HT and NE in hypothalamus; for the endocrine system, it raised the concentrations of E2 and FSH in serum, relieved the histological changes of uterus and adrenal gland and increased the expression of ER in uterus; for the immune system, it increased the thymus index and the expression of ER in spleen. CONCLUSIONS: Liquiritin improved menopausal syndrome in multiple ways by affecting the neuro-endocrine-immune network.

ApoL1 induces kidney inflammation through RIG-I/NF-κB activation.

The genetic variations of the apolipoprotein L1 (APOL1) gene are associated with non-diabetic kidney diseases. However, very little is known about the role of ApoL1 in glomerular damage. Here, we aimed to identify the function and mechanism of ApoL1 in glomerular damage. The mice were randomly divided into two groups: one group was intraperitoneally injected with phosphate buffer saline (PBS), while the other group was intraperitoneally injected with recombinant ApoL1 every other day for 3 months. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were used to demonstrate the effects of ApoL1 on kidney inflammation and injury. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses revealed that ApoL1-treated mice exhibited enhanced expression of various inflammation markers in the kidney and serum compared to the PBS-treated mice. Immunofluorescence staining revealed that ApoL1 accumulated in kidney podocytes. Treatment with ApoL1 dose-dependently increased the expression of inflammation markers and apoptotic markers. The abnormal gene expression associated with ApoL1-mediated podocyte inflammation was evaluated using microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the upregulated genes were enriched in the inflammation-related processes, such as the RIG-I/NF-κB signaling pathway. Consistently, the knockdown of RIG-I significantly mitigated the ApoL1-induced upregulation of inflammatory and apoptotic markers in the human podocytes. Additionally, the ApoL1-induced glomerular damage was attenuated in AAV-shRIG-I mice. Therefore, the effects of ApoL1 on glomerular damage may be, at least partially, through inducing abnormal expression of inflammatory molecules, which may have important implications for treatment of kidney diseases.

Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa.

OBJECTIVE: This study aims to select the most effective anti-Rheumatoid Arthritis (RA) component of flavonoids from Daphne genkwa Sieb. et Zucc. by anti-inflammatory and immunomodulatory effects in vitro, and to elucidate the mechanism. METHODS: The anti-inflammatory and immunomodulatory effects of total flavonoids (TF) and four flavonoid components (genkwanin, hydroxygenkwanin, luteolin and apigenin) were determined by pharmacological approach in LPS-induced RAW 264.7 macrophages and ConA-induced T lymphocytes. Principal component analysis (PCA) was used to obtain the optimal anti-RA component in vitro. Western blot and real-time quantitative PCR (q-PCR) were used to explore the mechanisms. Finally, the in vitro anti-RA effect was verified by human rheumatoid arthritis fibroblast-like synoviocytes (FLSs). RESULTS: TF and four flavonoids significantly reduced the expressions of NO, iNOS, TNF-α, IL-6, IFN-γ and IL-2. PCA showed that genkwanin was the most effective anti-RA component in vitro. Genkwanin inhibited nuclear factor-κB (NF-κB) pathway by decreasing the phosphorylation levels of IKK, IκB and NF-κB, and down-regulated the expressions of iNOS, COX-2 and IL-6 mRNA. Genkwanin also inhibited the abnormal proliferation of FLSs and down-regulated the secretions of NO and IL-6. CONCLUSION: The most effective anti-RA component was genkwanin. Genkwanin exerts anti-RA effect through down-regulating the activation of NF-κB pathway and mRNA expressions of inflammatory mediators, and also by inhibiting the abnormal proliferation of FLSs and its NO and IL-6 secretion levels.

Fatty acid-binding protein 3 contributes to ischemic heart injury by regulating cardiac myocyte apoptosis and MAPK pathways.

Fatty acid-binding protein 3 (FABP3), a low-molecular-weight protein, participates in lipid transportation, storage, signaling transduction, oxidation, and transcription regulation. Here, we investigated the expression and function of FABP3 in ischemic heart diseases and explored the mechanisms by which FABP3 affected remodeling after myocardial infarction (MI). We showed that ischemic or hypoxic conditions upregulated FABP3 expression in vivo and in vitro. Notably, overexpression of FABP3 induced more myocyte apoptosis in the infarction and border areas and aggravated cardiac dysfunction, with lower left ventricular ejection fraction. Meanwhile, overexpression of FABP3 drastically promoted death and apoptosis of neonatal rat ventricular cardiomyocytes under hypoxia. Furthermore, deficiency of FABP3 exerted protective effects against ischemic heart injuries by decreasing cardiac myocyte apoptosis and heart remodeling after MI. We found that overexpression of FABP3 upregulated the phosphorylation of MAPK signaling pathway and decreased phosphorylated Akt levels, which may account for the augmentation of apoptosis and remodeling after MI. To the best of our knowledge, this is the first study to demonstrate that deficiency of FABP3 would protect cardiac myocytes from apoptosis and alleviate cardiac remodeling after MI, suggesting FABP3 as a potential target to preserve cardiac function after MI. NEW & NOTEWORTHY It is an undisputable fact that myocyte apoptosis plays a crucial role in cardiac remodeling and the development of heart failure after myocardial infarction. Here, fatty acid-binding protein 3 deficiency improved myocardial structural remodeling and function by decreasing cell apoptosis and regulating MAPK signaling pathways. We suppose that fatty acid-binding protein 3 may be regarded as a potential intervention approach to preserve cardiomyocytes during myocardial infarction.

Decreased circulating catestatin levels are associated with coronary artery disease: The emerging anti-inflammatory role.

BACKGROUND AND AIMS: The neuropeptide catestatin (CST) is an endogenous nicotinic cholinergic antagonist that acts as pleiotropic cardiac protective hormone. This study investigated the association between CST and coronary artery disease (CAD) and the underlying mechanisms. METHODS AND RESULTS: The serum concentration of CST among 224 CAD patients and 204 healthy controls was compared, and its association with atherosclerosis severity in 921 CAD patients was further analyzed. Compared to healthy subjects, serum CST concentration was lower in patients with CAD [1.14 (1.05-1.24) ng/mL vs. 2.15 (1.92-2.39) ng/mL, p < 0.001] and was inversely correlated with disease severity (r = -0.208, p < 0.001). In cultured endothelial cells, CST suppressed TNF-α-elicited expression of inflammatory cytokines and adhesion molecules by activating angiotensin-converting enzyme-2 (ACE2). Administration of CST reduced leukocyte-endothelium interactions in vitro and in vivo, and attenuated the development of atherosclerotic in ApoE-/- mice fed a high-fat diet. These protective effects by CST were blocked by an ACE2 inhibitor. CONCLUSIONS: Serum CST concentration is lower in CAD patients and is inversely associated with the severity of atherosclerosis. CST acts as a novel anti-atherogenic peptide that inhibits inflammatory response and EC-leukocyte interactions via an ACE2-dependent mechanism.

Dectin-1 Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Macrophage Polarization and Neutrophil Infiltration.

BACKGROUND: Macrophage-associated immune response plays an important role in myocardial ischemia/reperfusion (IR) injury. Dectin-1, expressed mainly on activated myeloid cells, is crucial for the regulation of immune homeostasis as a pattern recognition receptor. However, its effects and roles during the myocardial IR injury remain unknown. METHODS: Genetic ablation, antibody blockade, or Dectin-1 activation, along with the adoptive bone marrow transfer chimeric model, was used to determine the functional significance of Dectin-1 in myocardial IR injury. Immune cell filtration and inflammation were examined by flow cytometry, quantitative real-time polymerase chain reaction, and immunohistochemistry. Moreover, Dectin-1+ cells were analyzed by flow cytometry in the blood of patients with ST-segment-elevation myocardial infarction and stable patients with normal coronary artery (control). RESULTS: We demonstrated that Dectin-1 expression observed on the bone marrow-derived macrophages is increased in the heart during the early phase after IR injury. Dectin-1 deficiency and antibody-mediated Dectin-1 inhibition led to a considerable improvement in cardiac function, accompanied by a reduction in cardiomyocyte apoptosis, which was associated with a decrease in M1 macrophage polarization and Ly-6C+ monocyte and neutrophil infiltration. Activation of Dectin-1 with its agonist had the opposite effects. Furthermore, Dectin-1 contributed to neutrophil recruitment through the regulation of Cxcl1 and granulocyte colony-stimulating factor expression. In addition, Dectin-1-dependent interleukin-23/interleukin-1ß production was shown to be essential for interleukin-17A expression by γδT cells, leading to neutrophil recruitment and myocardial IR injury. Furthermore, we demonstrated that circulating Dectin-1+CD14++CD16- and Dectin-1+CD14++CD16+ monocyte levels were significantly higher in patients with ST-segment-elevation myocardial infarction than in controls and positively correlated with the severity of cardiac dysfunction. CONCLUSIONS: Our results reveal a crucial role of Dectin-1 in the process of mouse myocardial IR injury and provide a new, clinically significant therapeutic target.