Characteristics, prognostic determinants of monocytes, macrophages and T cells in acute coronary syndrome: protocol for a multicenter, prospective cohort study.

BACKGROUND: Acute coronary syndrome(ACS) is the leading cause of mortality and disability worldwide. Immune response has been confirmed to play a vital role in the occurrence and development of ACS. The objective of this prospective, multicenter, observational study is to define immune response and their relationship to the occurrence and progressive of ACS. METHODS: This is a multicenter, prospective, observational longitudinal cohort study. The primary outcome is the incidence of major adverse cardiovascular events (MACE) including in-stent restenosis, severe ventricular arrhythmia, heart failure, recurrent angina pectoris, and sudden cardiac death, and stroke one year later after ACS. Demographic characteristics, clinical data, treatments, and outcomes are collected by local investigators. Furthermore, freshly processed samples will be stained and assessed by flow cytometry. The expression of S100A4, CD47, SIRPα and Tim-3 on monocytes, macrophages and T cells in ACS patients were collected. FOLLOW-UP: during hospitalization, 3, 6 and 12 months after discharge. DISCUSSION: It is expected that this study will reveal the possible targets to improve the prognosis or prevent from occurrence of MACE in ACS patients. Since it's a multicenter study, the enrollment rate of participants will be accelerated and it can ensure that the collected data are more symbolic and improve the richness and credibility of the test basis. ETHICS AND DISSEMINATION: This study has been registered in Chinese Clinical Trial Registry Center. Ethical approval was obtained from the Affiliated Hospital of Guizhou Medical University. The dissemination will occur through the publication of articles in international peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200066382.

LncRNA HOTTIP facilitates osteogenic differentiation in bone marrow mesenchymal stem cells and induces angiogenesis via interacting with TAF15 to stabilize DLX2.

AIM: The molecular mechanism of differentiation in bone marrow mesenchymal stem cells (BMSCs) preserves to be further elucidated. LncRNA HOTTIP has been proven to accelerate osteogenic differentiation, but the regulation mechanism is still unclear. METHODS: The human BMSCs (hBMSCs) were isolated and identified by the antigen CD29, CD34, CD44, CD45, and CD90 through flow cytometry. The osteogenic state was determined by the ALP Detection Kit and Alizarin red staining. The tube formation was observed under a microscope. HOTTIP expression level, DLX2 and TAF15, Wnt/ß-catenin pathway, and transcriptional markers in osteogenesis and angiogenesis were examined with Western blot and RT-qPCR, respectively. The combination of TAF15 with lncRNA HOTTIP and DLX2 was detected by RNA immunoprecipitation (RIP) and RNA pulldown assays. RESULTS: The outcomes revealed that HOTTIP was noticeably up-regulated accompanied by the osteogenic transcriptional factor in the process of osteoblast differentiation and angiogenesis. Besides, HOTTIP enhanced alkaline phosphatase (ALP) activity, accelerated osteogenic differentiation and angiogenesis along with up-regulation of osteogenic and angiogenic-related gene expression, by interaction with TAF15 to stabilize DLX2. CONCLUSION: Taken together, our outcomes reveal that lncRNA HOTTIP accelerated osteogenic differentiation and angiogenesis by interaction with TAF15 to stabilize DLX2.

[Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology].

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products.

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus exhibit antiatherosclerotic capacity by suppressing lipid uptake, cholesterol esterification, and/or promoting cholesterol ester hydrolysis and cholesterol efflux. This review summarizes recent findings on these three biologic processes and natural products with demonstrated potential to target such processes. Discussed also are potential future directions for studying the mechanisms of foam cell formation and the development of foam cell-targeted therapeutic strategies.

MiR-125b inhibits cardiomyocyte apoptosis by targeting BAK1 in heart failure.

BACKGROUND: Although miR-125b plays a crucial role in many human cancers. However, its function in heart failure (HF) remains unclear. Our study aimed to investigate its involvement in heart failure. METHODS: In this study, the mouse HF model was successfully constructed through transverse aortic constriction (TAC) operation. Changes in mRNA and protein levels in isolated myocytes and heart tissues were examined using qRT-PCR, Western blot and Immunohistochemical staining and immunofluorescent staining. Changes in cardiac functions were examined using ultrasound. Interactions between miR-125b and BAK1 was analyzed using the luciferase reporter assay. Cardiomyocyte apoptosis was evaluated using the TUNEL staining. RESULTS: We found that miR-125b expression was significantly downregulated in myocardial tissues of HF mice. Moreover, miR-125b upregulation in HF mice injected with agomir-125b efficiently ameliorated cardiac function. Further, miR-125b upregulation significantly decreased the protein levels of apoptosis-related makers c-caspase 3 and Bax, while increased Bcl-2 expression. In addition, BAK1 was identified as a direct target of miR-125b. As expected, BAK1 overexpression observably reversed the effect of agomir-125b on cardiac function and on the expression of apoptosis-related makers in the heart tissues of HF mice. CONCLUSIONS: Taken together, miR-125b overexpression efficiently attenuated cardiac function injury of HF mice by targeting BAK1 through inhibiting cardiomyocyte apoptosis, suggesting that miR-125b/BAK1 axis might be a potential target for the diagnosis or treatment of HF.

Hepatocytes derived increased SAA1 promotes intrahepatic platelet aggregation and aggravates liver inflammation in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the pathological manifestation of metabolic syndrome in liver. Its pathological changes may evolve from the initial simple steatosis to non-alcoholic steatohepatitis, liver fibrosis and even liver cancer. Numerous studies have proved that platelets play a vital role in liver disease and homeostasis. Particularly, anti-platelet therapy can reduce intrahepatic platelet aggregation and improve the inflammation of fatty liver. Previous study has also confirmed that SAA is a gene closely related to high-fat diet (HFD) induced obesity, and SAA1 can promote liver insulin resistance induced by Palmitate or HFD. Here, we found that SAA1 treated platelets presented increased sensitivity of platelet aggregation, enhanced activation and increased adhesion ability, and such function was partly dependent on Toll-Like Receptor (TLR) 2 signaling. In addition, blocking SAA1 expression in vivo not only inhibited platelet aggregation in the liver tissues of NAFLD mice, but also alleviated the inflammation of fatty liver. In conclusion, our findings identify that HFD-induced hepatic overexpressed SAA1 aggravates fatty liver inflammation by promoting intrahepatic platelet aggregation, these results also imply that SAA1 may serve as a potential target for ameliorating NAFLD.

Thyroid Hormone Metabolite 3-Iodothyronamine (T1AM) Alleviates Hypoxia/Reoxygenation-Induced Cardiac Myocyte Apoptosis via Akt/FoxO1 Pathway.

BACKGROUND The thyroid hormone metabolite 3-iodothyronamine (T1AM) is rapidly emerging as promising compound of decreasing heart rate and lowering cardiac output. The aim of our study was to fully understand the molecular mechanism of T1AM on cardiomyocytes and its potential targets in cardiovascular diseases. MATERIAL AND METHODS We developed an in vitro myocardial ischemia-reperfusion injury model of AC-16 cells by hypoxia-reoxygenation injury. Cell viability of AC-16 cells was detected using CCK-8 assay and apoptosis was detected by flow cytometry. RNA-seq was used to characterize the gene expression in H/R-induced AC-16 cells after T1AM treatment. The mRNA levels of FoxO1, PPARalpha, Akt, and GCK and the protein levels of PPARalpha, GCK, and components of the Akt/FoxO1 pathway were detected by qRT-PCR and Western blotting, respectively. RESULTS Exogenous T1AM increased the H/R-induced AC-16 cell viability in a relatively low concentration. A total of 210 DEGs, including 142 upregulated and 68 downregulated genes, were determined in H/R-induced AC-16 cells treated with or without T1AM. A Venn diagram showed 135 common DEGs. The FoxO signaling pathway was identified via KEGG enrichment analysis of these 135 DEGs. Moreover, T1AM mediated hypometabolism and reduced the apoptosis of H/R-induced AC-16 cells via the Akt/FoxO1 pathway. CONCLUSIONS Exogenous T1AM protects against cell injury induced by H/R in AC-16 cells via regulation of the FoxO signaling pathway. Our results suggest that T1AM can play a preventive role in myocardial H/R injury and also provide new insight for clinical management of AMI patients.

miR-1322 regulates ChREBP expression via binding a 3'-UTR variant (rs1051943).

The carbohydrate response element-binding protein (ChREBP), also referred to as MLXIPL, plays a crucial role in the regulation of glucose and lipid metabolism. Existing studies have shown an association between genetic variations of the ChREBP gene and lipid levels, such as triglycerides and high-density lipoprotein cholesterol. However, mechanistic studies of this association are limited. In this study, bioinformatic analysis revealed that the polymorphism rs1051943A occurs in the complementary binding sequence of miR-1322 in the ChREBP 3'-untranslated region (UTR). Studies of potential mechanisms showed that the A allele could facilitate miR-1322 binding, and luciferase activity significantly decreased when co-transfected with a ChREBP 3'-UTR luciferase reporter vector and miR-1322 mimics in HepG2 cells. Furthermore, miR-1322 significantly regulated the expression of ChREBP downstream genes and reduced the synthesis of lipids. The expression of miR-1322 was up-regulated by glucose and palmitic acid stimulation. Population studies showed that rs1051943-A allele was only found in the Han Chinese and Uighur ethnic groups, different from European populations (G allele frequency = 0.07). In summary, we provide evidence that the rs1051943 A allele creates a functional miR-1322 binding site in ChREBP 3'-UTR and post-transcriptionally down-regulates its expression, possibly associated with levels of plasma lipids and glucose.

Essential Oil from Fructus Alpiniae Zerumbet Protects Human Umbilical Vein Endothelial Cells In Vitro from Injury Induced by High Glucose Levels by Suppressing Nuclear Transcription Factor-Kappa B Signaling.

BACKGROUND In China, the essential oil of the fruit, Fructus Alpiniae zerumbet (FAZ), is used to treat cardiovascular diseases. Recent in vitro studies have shown that the essential oil of FAZ (EOFAZ) can protect endothelial cells from injury. Because of the prevalence of diabetes mellitus and its effects on the cardiovascular system, the aim of this study was to investigate the mechanism of the effects of EOFAZ on human umbilical vein endothelial cells (HUVECs) treated with high levels of glucose in vitro. MATERIAL AND METHODS The lactate dehydrogenase (LDH) leakage assay was used to detect HUVEC injury. Tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and nuclear transcription factor-kappa B (NF-κB) p65 subunit DNA-binding activity was detected. The expression of NF-κB pathway-associated proteins, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was studied by Western blotting. The cellular location of NF-κB in HUVECs was evaluated using immunofluorescence. RESULTS Cell viability and LDH leakage assays showed that high glucose-induced HUVEC injury was reduced by EOFAZ. High glucose-induced secretion of IL-8, TNF-α, ICAM-1, and VCAM-1 was reduced, and translocation of the p65 subunit of NF-κB to the endothelial cell nucleus was inhibited by EOFAZ. Western blotting confirmed that EOFAZ blocked the activation of NF-κB induced by high glucose levels. EOFAZ reduced high glucose-induced p65/DNA binding to inhibit NF-κB activation. CONCLUSIONS The findings of this in vitro study showed that treatment of HUVECs with EOFAZ had a protective role against the effects of high glucose levels via the NF-κB signaling pathway.

Cortical functional activity in patients with generalized anxiety disorder.

BACKGROUND: The neurological correlates of Generalised Anxiety Disorder (GAD) are not well known, however there is evidence of cortical dysregulation in patients with GAD. The aim of the study was to examine cortical functional activity in different cerebral regions in patients with GAD using electroencephalogram (EEG) nonlinear analysis to evaluate its contribution of anxiety severity. METHODS: The cohorts consisted of 64 patients diagnosed with GAD as classified by the Structured Clinical Interview for the Diagnostic and Statistical Manual of the American Psychiatric Association-IV-TR. Anxiety severity was assessed using the Hamilton Rating Scale for Anxiety (HAMA) severity score, with 7 ≤ scores ≤ 17 indicating mild anxiety as A group (n = 31) and 18 and above indicating moderate-severe anxiety as B group (n = 33). Participants with clinical levels of depression symptoms were excluded. A healthy control group comprising 30 participants was matched for age and gender. Closed eyes EEGs were conducted, and between-group differences on non-linear parameter Correlation Dimension (D2) were analyzed. The association of D2 value with HAMA scores was analyzed using multiple linear stepwise regression. RESULTS: Compared with the control group, D2 values were increased in anxiety groups (P < .05). For those with mild anxiety, this difference occurred in the left prefrontal regions (P < .05). For those with moderate-severe anxiety, significantly greater D2 values were observed in all of the cerebral regions, especially in the left cerebral regions and right temporal lobe (P < .01). When compared with those with mild anxiety, D2 values were significantly greater for those with moderate-severe anxiety in the right temporal lobe and all left cerebral regions except for left occipital lobe (P < .05). A positive correlation was observed between D2 values and moderate-severe anxiety HAMA scores. CONCLUSIONS: The increased D2 values were found in the majority of cerebral regions in GAD patients, especially in the left cerebral regions and the right temporal lobe. The increased GAD severity positively correlates to the D2 values in a larger number of cerebral regions. This analysis method can potentially be used as a complementary tool to examine dysfunctional cortical activity in GAD.

Effect of Ginkgo biloba extract on experimental cardiac remodeling.

BACKGROUND: To investigate the ameliorated effects of an extract of Ginkgo biloba extract (GBE) on experimental cardiac remodeling in rats induced by acute cardiac infarction, and further explore the mechanism concentrated on myocardial type I collagen, transforming growth factor beta 1 (TGF-ß1), matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and provide the experimental data for clinical application of GBE. METHODS: Rats were divided into five groups (n = 20) as following: sham operation group (group A), acute myocardial infarction model group (group B), acute myocardial infarction model + aspirin (10 mg/kg) treatment group (group C), acute myocardial infarction model + captopril (20 mg/kg) treatment group (group D) and acute myocardial infarction model + Ginkgo biloba extract (100 mg/kg) treatment group (group E). The rat acute myocardial infarction model was reproduced by ligaturing the left anterior descending artery excluding the sham operation group which did not ligation only completed the operational process. Each group was further subdivided into treatment regimens lasting 4 weeks and 8 weeks. Immunohistochemistry and real-time polymerase chain reaction (PCR) methods were used to detect the protein expression and mRNA transcriptional levels of rat myocardial TGF-ß1, type I collagen, MMP-2 and MMP-9. RESULTS: Compared with group B, regardless of the length of treatment (4 or 8 weeks), the TGF-ß1, MMP-2 and MMP-9 mRNA transcriptional levels, and the protein expression levels of type I collagen, MMP-2 and MMP-9 in groups D, C and E were significantly decreased (P < 0.01). Furthermore, the mRNA expression levels of TGF-ß1 in groups D, C and E were significantly lower after 8 weeks compared to after 4 weeks (P < 0.01), as were the expression levels of type I collagen in groups D, C and E (P < 0.05). There was no statistically significant difference in the protein expression levels of MMP-2 and MMP-9 between groups E and C. CONCLUSIONS: GBE could inhibit experimental rat myocardial remodeling after acute myocardial infarction via reduced transcription of TGF-ß1, MMP-2 and MMP-9 genes and by the decreased expression of type I collagen, MMP-2 and MMP-9 proteins in myocardial cells.

The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.

BACKGROUND: Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. RESULTS: Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01). CONCLUSIONS: These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

[Ameliorated effects of cyclovirobuxine D on oxidative stress and energy metabolism in experimental cardiac injured rats induced by sympathetic overactivity in vivo].

OBJECTIVE: To investigate the ameliorated effect of CVB-D on oxidative stress and energy metabolism in experimental cardiac injuried rats induced by sympathetic overactivity in vivo. METHODS: SD rats were randomly divided into five groups as following: control group, model group, Vitamin E 150 mg/kg group, CVB-D low dose and high dose groups, respectively. The rat experimental cardiac injury model was established by exposed to norepinephrine (NE) 3 mg/kg by ip for 16 d. The drugs were administrated to rat for 16 d by ig. The body weight of rats were monitored during all of the experimental period. At the designing ending-time point the indexes were assayed as following: cardiac index, hydroxyproline, histopathologically examination, oxidative stress ( MDA, SOD, CAT, GSH-Px and T-AOC) and energy metabolism indicatricle ( Na+, K(+) -ATPase, and Ca2+, Mg(2+) -ATPase). RESULTS: After exposed with NE for 16 d, the rats of model group was appeared dysfunction of oxidative stress and energy metabolism such as decreasing body weight, increasing cardiac index and hydroxyproline in cardiac tissue, decreasing Na+, K(+) -ATPase and Ca(2+), Mg(2+) -ATPase activities, and deteriorating the oxidative stress. Treated with CVB-D could ameliorate all of the exacerbated indexes. CONCLUSION: CVB-D has protective effect against oxidative stress and energy metabolism in rats of experimental myocardial injury induced by sympathetic overactivity.

[Protective effects of CVB-D on cardiac myocytes injury induced by high sympathesis activity in vitro].

OBJECTIVE: To investigate the protective effect of CVB-D on cardiac myocytes injury induced by high sympathesis activity and its relationship with oxidative stress. METHODS: Primary culture cardiac myocyte of new-born rat was injuried by NE and then incubated with VE and CVB-D (10 and 50 micromol/L). Indexes of cardiac myoctye injury were assayed by morphologic change, MTT, and LDH leakage ratio. The activity of SOD and the content of MDA were investigated to identify oxidation and antioxygen. RESULTS: CVB-D (10 and 50 micromol/L) significantly increased the cell survival rate,and reduced the LDH leakage rate. CVE-D (50 micromol/L) significantly increased the activity of SOD, and decreased content of MDA in injuried cell. CONCLUSION: CVB-D has protective effect against myocardial injury induced by high sympathesis activity, the mechanism involves in ameliorating oxidative stress.

Associations between waist circumference, central obesity, and the presence of non-valvular atrial fibrillation patients with heart failure.

Background: Reportedly, there is a clear correlation between waist circumference (WC) and atrial fibrillation (AF). However, there is no specific discussion about the relationship between WC and non-valvular AF (NVAF) patients with heart failure. Our main purpose was to study the relationship between WC, central obesity (CO), and NVAF patients with heart failure. Methods: This is a retrospective cohort study. A total of 3,435 patients with NVAF in the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2017 were enrolled. The targeted independent variable and the dependent variable were WC and CO and the presence of NVAF with heart failure, respectively. Univariate, multiple regression, and subgroup analyses were used to analyze their relationship. We used the receiver operating characteristic (ROC) curve to choose the better predictor of NVAF with heart failure between WC and CO and calculated the proposed cut-off value of WC in males and female separately. Results: The identified risk factors of NVAF with heart failure were sex, height, WC, CO, body mass index (BMI), fasting blood glucose (FBG), homocysteine (HCY), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), hypertension, diabetes mellitus (DM), stroke, vascular disease, and plaque. Then, a binary logistic regression model indicated that the occurrence of NVAF patients with heart failure increased 10% with WC increasing 1 cm and had a 2.8-fold increased risk with CO compared to those without. The predictive value [area under the ROC curve (AUC)], specificity, sensitivity, and accuracy of WC for the disease risk of NVAF with heart failure were higher than those of CO. The proposed cut-off value of WC was 91.85 cm for males and 93.15 cm for females. The diagnostic value of WC for NVAF with heart failure was higher for females than it was for males. Conclusions: Our research found that WC is related to the presence of heart failure in the patients with NYAF and can predict the presence of NVAF with heart failure. Our findings may help to improve the treatment and care strategies of NVAF individuals with abdominal obesity.

Analyzing the changing trend of corneal biomechanical properties under different influencing factors in T2DM patients.

To analyze the changing trend of CH and CRF values under different influencing factors in T2DM patients. A total of 650 patients with T2DM were included. We discovered that the course of T2DM, smoking history, BMI, and FBG, DR, HbA1c, TC, TG, and LDL-C levels were common risk factors for T2DM, while HDL-C levels were a protective factor. Analyzing the CH and CRF values according to the course of diabetes, we discovered that as T2DM continued to persist, the values of CH and CRF gradually decreased. Moreover, with the increase in FBG levels and the accumulation of HbA1c, the values of CH and CRF gradually decreased. In addition, in patients with HbA1c (%) > 12, the values of CH and CRF decreased the most, falling by 1.85 ± 0.33 mmHg and 1.28 ± 0.69 mmHg, respectively. Compared with the non-DR group, the CH and CRF values gradually decreased in the mild-NPDR, moderate-NPDR, severe-NPDR and PDR groups, with the lowest CH and CRF values in the PDR group. In patients with T2DM, early measurement of corneal biomechanical properties to evaluate the change trend of CH and CRF values in different situations will help to identify and prevent diabetic keratopathy in a timely manner.

The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction.

BACKGROUND: There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction. METHODS: Rats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio. RESULTS: In the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups. CONCLUSIONS: These results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial infarction and depression. This mechanism may be germane to understanding this relationship in humans.

Altered cardiac autonomic nervous function in depression.

BACKGROUND: Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia. METHODS: Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson's correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)). RESULTS: The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly supraventricular arrhythmias. CONCLUSIONS: Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease.

[Effects of ginkgo flavone aglycone on oxidized LDL induced oxidative injury of human aortic endothelial cells].

OBJECTIVE: To observe the effects of ginkgo flavone aglycone (GA) on oxidized low-density lipoprotein (ox-LDL) induced oxidative injury of human aortic endothelial cells (HAECs) and its mechanisms. METHODS: HAECs were in vitro cultured. Then they were divided into 6 groups, i.e., the vehicle control group, the ox-LDL group, the GA 30 mg/L group, the GA 60 mg/L group, the GA 90 mg/L group, and the Vit E group. The oxidative injury model was duplicated in the rest 5 groups by adding 150 mg/L ox-LDL except the vehicle control group. GA was added as intervention at corresponding dose to the GA 30 mg/L group, the GA 60 mg/L group, and the GA 90 mg/L group. Vit E at 200 micromol/L was administered to those in the Vit E group. The survival rate of HAECs was detected by MTT. The contents of reactive oxygen species (ROS) in HAECs were determined by CM-H2DCFDA fluorescent probe. The contents of NADPH oxidase were detected by ELISA. The levels of malondialdehyde (MDA) were measured by thiobarbituric acid (TBA) test. The contents of nitric oxide (NO) were determined by Griess reagent method. The contents of superoxide dismutase (SOD) were detected by xanthine oxidase method. RESULTS: Compared with the vehicle control group (100.00%), the cell survival rate in the ox-LDL group (70.68%) obviously decreased (P <0.05). The cell survival rate was 88. 95% in the VitE group, 83.25% in the GA 30 mg/L group, and 94.93% in the GA 60 mg/L group, obviously higher than that of the ox-LDL group (70.68%, P <0.05). The optimal effects were shown in the GA 60 mg/L group. Compared with the vehicle control group, the contents of ROS, MDA, and NADPH oxidase increased, the contents of NO and the SOD activity decreased in the ox-LDL group, showing statistical difference (P <0.05). Compared with the ox-LDL group, the contents of ROS, MDA, and NADPH oxidase decreased, the NO content and the SOD activity increased in the GA 30 mg/L group, the GA 60 mg/L group, and the Vit E group, showing statistical difference (P <0.05). The optimal effects were shown in the GA 60 mg/L group. CONCLUSIONS: GA could obviously inhibit ox-LDL induced synthesis of ROS, lower the contents of MDA, and elevate the levels of NO. Its mechanisms might be associated with increasing the activity of SOD and lowering the activity of NADPH oxidase.