Depression and anxiety symptom network structure among patients with coronary heart disease and association with quality of life: protocol for a multicentre cross-sectional and prospective longitudinal study.

BACKGROUND: Anxiety and depression are critical mental health problems among persons with coronary heart disease (CHD). The range of symptoms is an important stressor for adverse cardiovascular events, and these symptoms can be involved in various ways during the course of CHD. However, the characteristics and mechanisms of comorbidity between the two mental states from the viewpoint of symptom interactions in patients with CHD remain unclear. Therefore, we aim to apply a symptom-oriented approach to identify core and bridge symptoms between anxiety and depression in a population with CHD and to identify differences in network structure over time and symptomatic link profiles. METHODS AND ANALYSIS: We designed a multicentre, cross-sectional, longitudinal study of anxiety and depression symptoms among patients with CHD. We will evaluate degrees of symptoms using the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire and the WHO Quality of Life-Brief version. Patients will be followed up for 1, 3 and 6 months after baseline measurements. We will analyse and interpret network structures using R software and its packages. The primary outcomes of interest will include centrality, bridge connections, estimates, differences in network structures and profiles of changes over time. The secondary outcome measures will be the stability and accuracy of the network. By combining cross-sectional and longitudinal analyses, this study should elucidate the central and potential causative pathways among anxiety and depression symptom networks as well as their temporal stability in patients with CHD. ETHICS AND DISSEMINATION: The project conforms to the ethical principles enshrined in the Declaration of Helsinki (2013 amendment) and all local ethical guidelines. The ethics committee at the University of South China approved the study (Approval ID: 2023-USC-HL-414). The findings will be published and presented at conferences for widespread dissemination. TRIAL REGISTRATION NUMBER: ChiCTR2300075813.

Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1-b][1,3]thiazines from 2-Mercaptobenzimidazoles and ß-CF3-1,3-Enynes.

A base-controlled divergent cyclization between 2-mercaptobenzimidazoles and ß-CF3-1,3-enynes providing either trifluoromethylated or fluorinated benzo[4,5]imidazo[2,1-b][1,3]thiazines has been developed. The ß-CF3-1,3-enyne, as a three-carbon synthon, underwent a 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU)-catalyzed tandem hydroamination/intramolecular hydrothiolation to give CF3-substituted 3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazine, whereas reaction with KOH afforded fluorinated 4H-benzo[4,5]imidazo[2,1-b][1,3]thiazine exclusively. In addition, the synthetic utility of this methodology was showcased through a variety of downstream derivatizations.

Synthesis of CF3-Substituted Alkylamines, 1,2-Bisazoles, and 1,4,5,6-Tetrahydro-1,2,4-triazines from Newly Designed Tetrazole-Activated Trifluoromethyl Alkenes.

A new class of Michael acceptor, tetrazolyl-trifluoromethyl alkenes, has been discovered. They readily undergo Michael-type addition instead of addition-elimination reaction with aliphatic amines and azoles to furnish ß-trifluoromethyl alkylamines and CF3-substituted 1,2-bisazole derivatives, respectively. Additionally, some of the products are capable of engaging in microwave-assisted intramolecular denitrogenative annulation, leading to the formation of CF3-substituted 1,4,5,6-tetrahydro-1,2,4-triazines that are otherwise difficult to access by other methodologies.

N-Trifluoropropylation of Azoles through N-Vinylation and Sequential Hydrogenation.

Installing a fluoroalkyl group onto the nitrogen atom of azoles represents a potential strategy for lead optimization in medicinal chemistry. Herein, we describe a method for the N-trifluoropropylation of azoles. This process is accomplished using a combination of regioselective N-vinylation and sequential hydrogenation. The two-step sequence is applicable to a diverse set of azoles and tolerates a wide range of functionalities. In addition, we showcase its practicability and utility through the gram-scale synthesis and the late-stage modification of a complex molecule.

Proangiogenesis effects of compound danshen dripping pills in zebrafish.

BACKGROUND: The compound Danshen Dripping Pill (CDDP), which is a mixture of extracts from Radix Salviae and Panax notoginseng, is a patented traditional Chinese medicine that is widely used in multiple countries for relieving coronary heart disease (CHD), but its pharmacological mechanism has not been fully elucidated. In this study, we screened the key pharmacological pathways and targets of CDDP that act on CHD using a network pharmacology-based strategy, and the angiogenic activity of CDDP was directly visually investigated in zebrafish embryos in vivo. METHODS: The potential therapeutic targets and pathways were predicted through a bioinformatics analysis. The proangiogenic effects of CDDP were examined using vascular sprouting assays on subintestinal vessels (SIVs) and optic arteries (OAs) as well as injury assays on intersegmental vessels (ISVs). Pharmacological experiments were applied to confirm the pathway involved. RESULTS: Sixty-five potential therapeutic targets of CDDP on CHD were identified and enriched in the PI3K/AKT and VEGF/VEGFR pathways. An in vivo study revealed that CDDP promoted angiogenesis in SIVs and OAs in a dose-dependent manner and relieved the impairments in ISVs induced by lenvatinib, a VEGF receptor kinase inhibitor (VRI). In addition, Vegfaa and Kdrl expression were significantly upregulated after CDDP treatment. Furthermore, the proangiogenic effect of CDDP could be abolished by PI3K/AKT pathway inhibitors. CONCLUSIONS: CDDP has a proangiogenic effect, the mechanism of which involves the VEGF/VEGFR and PI3K/AKT signaling pathways. These results suggest a new insight into the cardiovascular protective effect of CDDP.

1,2-Dicarbofunctionalization of Trifluoromethyl Alkenes with Pyridinium Salts via a Cycloaddition/Visible-Light-Enabled Fragmentation Cascade.

Although trifluoromethyl alkenes have great synthetic potential, their 1,2-difunctionalization has been a challenge. In this Letter, we disclose the first 1,2-dicarbofunctionalization of trifluoromethyl alkenes with pyridinium salts via a cascade process involving a base-promoted [3 + 2] cycloaddition followed by a visible-light-mediated Norrish-type-II fragmentation. This protocol allows for the formation of pyridines bearing a trifluoromethyl-substituted quaternary center in moderate to excellent yields under mild conditions.

[Effect of advanced glycation end products on the function and angiogenesis of adipose tissue-derived stem cells and the protective effect of danhong injection: an experimental study].

UNLABELLED: OBJECTIVE To investigate the effect of Nepsilon-(carboxymethyl) lysine albumin (CMLs), a primary advanced glycation end products (AGEPs) isoform in diabetic body, on the function and angiogenesis of adipose tissue-derived stem cells (ADSCs) and the protective effect of Danhong Injection (DH). METHODS Human ADSCs were cultured and separated from human subcutaneous fatty tissue using enzymatic digestion and centrifugation. The morphology was observed using optical microscope and differentiation capacities assessed. Cells were exposed to 5 different interventions respectively for 24 h, i.e., PBS, 60 1 microg/mL BSA, 60 microg/mL CML-BSA, 100 microL/mL DH, and 60 micro./mL CML-BSA +100 microL/mL DH. Their effect on the proliferation, migration, apoptosis, and secretion were observed using WST-1 assay, Transwell assay, Annexin V-FITC/PI flow meter test reagent kit, human VEGF reagent kit, ELISA reagent kit, respectively. The effect on ADSCs angiogenesis was observed by in vitro angiogenesis test. RESULTS: Compared with the BSA group, the capacities of proliferation and migration could be significantly inhibited by CML-BSA, the apoptosis promoted, the secretion of VEGF reduced, and the angiogenesis of ADSCs weakened (P < 0.05). Compared with the blank control group, 100 microL/mL DH could significantly promote the proliferation and migration capacities of ADSCs, inhibit apoptosis of ADSCs, increase the secretion of VEGF, and improve the angiogenesis of ADSCs (P < 0.05). Compared with the CML-BSA group, the inhibition of CML-BSA on the proliferation and migration capacities of ADSCs could be significantly reversed, the promotion of CML-BSA on the apoptosis of ADSCs improved, the secretion of VEGF increased, and the angiogenesis of ADSCs elevated (P < 0.05). CONCLUSION: clusion CMLs could significantly inhibit the proliferation and migration capacities of ADSCs, promote their apoptosis, and inhibit their angiogeneses, which could be improved by DH.

Circulating miR-214 is associated with the severity of coronary artery disease.

OBJECTIVE: To study whether miR-214 is regulated in coronary artery disease (CAD) patients and whether placental growth factor (PLGF) is a possible target for miR-214 in atherosclerosis. METHODS: Circulating miR-214 was measured by quantitative PCR using RNA isolated from 40 patients with CAD, including 12 with stable angina pectoris, 16 with unstable angina pectoris and 12 with acute myocardial infarction, and 15 controls without CAD. Plasma level of PLGF was measured by ELISA. RESULTS: The miR-214 level was significantly lower in CAD patients compared with that in controls (P < 0.01). Compared to controls, patients with unstable angina pectoris (UAP, 38.6±9.1 pg/mL) and acute myocardial infarction (AMI, 46.3±13.4 pg/mL) had significantly higher level of plasma PLGF, but not those with stable angina pectoris (SAP; P = 0.012, UAP vs. Control; P = 0.005, AMI vs. Control). In patients with AMI, the plasma level of miR-214 was positively correlated to that of PLGF. CONCLUSIONS: The results suggest that miR-214 is a beneficial microRNA for CAD patients. Loss of its protection may lead to increased PLGF levels and worsening atherosclerosis. Circulating miR-214 is a promising biomarker for alerting severe CAD.

Dysfunction of AQP7 in the periadventitial fat: A novel trigger of atherosclerosis.

Vascular adventitial lesion as a new etiological factor of atherosclerosis (AS) has been confirmed by the results of several different animal models, and some evidence supports adventitial inflammation as the main cause, but the exact mechanism is still elusive. The data from some studies confirm that some link exists between the adventitial inflammation (which also might happen in the periadventitial fat) and atherosclerotic lesions. Aquaporin7 (AQP7) as an aquaglyceroporin, which regulates the permeation of glycerol through the cell membrane and located in the adipose tissue, shows some relationship with obesity. The result of the studies about AQP7-knockout mice and different expression of AQP7 in the cutaneous abdominal adipose tissue among people with different body types proved this phenomenon. Meanwhile, some degree of dysfunction of AQP7 has been proved in the obese. Until now, no study has shown us the data on the correlation of the expression of AQP7 in the periadventitial fat with the severity of atherosclerotic lesions. It is proposed that dysfunction of AQP7 in the periadventitial fat may trigger the adventitial inflammation. Attempts to confirm this hypothesis may lead to new directions in the study of the pathogenesis of AS and the development of a novel agent for this disorder.

Vicious cycle composed of gut flora and visceral fat: a novel explanation of the initiation and progression of atherosclerosis.

Microorganisms infection was thought to be associated with atherosclerosis (AS), but the results of trials investigating antibiotic therapy in patients with coronary artery disease were controversial. Recently, a series of studies explored the relationship between gut flora and obesity, which showed that western-style diet (high fat) could induce imbalanced ratio of the Firmicutes versus the Bacteroidetes in the gut of germ-free mice and human beings, and gut flora could promote obesity through several novel pathways, such as inhibition of fasting-induced adipocyte factor. Meanwhile, data from some studies confirm that some link exists between the abdominal obesity and satiety centers (hindbrain and hypothalamus) with neurotransmitters and hormones. All of the above showed some connection between western-style diet, gut flora, visceral fat, and satiety centers, but until now, no study has shown us the exact mechanism about it. It is proposed that the vicious cycle composed of gut flora and visceral fat may initiate and promote AS. Attempts to confirm this hypothesis may lead to new directions in the study of the pathogenesis of AS and the development of novel strategies for the treatment of AS.