Exploration of the Potential Biomarker FNDC5 for Discriminating Heart Failure in Patients with Coronary Atherosclerosis.

Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.

Electrochemical Azidocyanation of Alkenes.

The difunctionalization of alkenes-a process that installs two functional groups in a single operation and transforms chemical feedstocks into value-added products-is one of the most appealing synthetic methods in contemporary chemistry. However, the introduction of two distinct functional groups via two readily accessible nucleophiles remains a formidable challenge. Existing intermolecular alkene azidocyanation methods, which primarily focus on aryl alkenes and rely on stoichiometric chemical oxidants. We report herein an unprecedented electrochemical strategy for alkene azidocyanation that is compatible with both alkyl and aryl alkenes. This is achieved by harnessing the finely-tuned anodic electron transfer and the strategic selection of copper/ligand complexes. The reactions of aryl alkenes were rendered enantioselective by employing a chiral ligand. Crucially, the mild conditions and well-regulated electrochemical process assure exceptional tolerance for various functional groups and substrate compatibility with both terminal and internal alkyl alkenes.

Cu-Electrocatalytic Diazidation of Alkenes at ppm Catalyst Loading.

The 1,2-diamine motif is prevalent in natural products, small-molecule pharmaceuticals, and catalysts for asymmetric synthesis. Transition metal catalyzed alkene diazidation has evolved to be an attractive strategy to access vicinal primary diamines but remains challenging, especially for practical applications, due to the restriction to a certain type of olefins, the frequent use of chemical oxidants, and the requirement for high loadings of metal catalysts (1 mol % or above). Herein we report a scalable Cu-electrocatalytic alkene diazidation reaction with 0.02 mol % (200 ppm) of copper(II) acetylacetonate as the precatalyst without exogenous ligands. In addition to its use of low catalyst loading, the electrocatalytic method is scalable, compatible with a broad range of functional groups, and applicable to the diazidation of α,ß-unsaturated carbonyl compounds and mono-, di-, tri-, and tetrasubstituted unactivated alkenes.

Electrochemical C-H phosphorylation of arenes in continuous flow suitable for late-stage functionalization.

The development of efficient and sustainable methods for carbon-phosphorus bond formation is of great importance due to the wide application of organophosphorus compounds in chemistry, material sciences and biology. Previous C-H phosphorylation reactions under nonelectrochemical or electrochemical conditions require directing groups, transition metal catalysts, or chemical oxidants and suffer from limited scope. Herein we disclose a catalyst- and external oxidant-free, electrochemical C-H phosphorylation reaction of arenes in continuous flow for the synthesis of aryl phosphorus compounds. The C-P bond is formed through the reaction of arenes with anodically generated P-radical cations, a class of reactive intermediates remained unexplored for synthesis despite intensive studies of P-radicals. The high reactivity of the P-radical cations coupled with the mild conditions of the electrosynthesis ensures not only efficient reactions of arenes of diverse electronic properties but also selective late-stage functionalization of complex natural products and bioactive compounds. The synthetic utility of the electrochemical method is further demonstrated by the continuous production of 55.0 grams of one of the phosphonate products.

Berberine on the Prevention and Management of Cardiometabolic Disease: Clinical Applications and Mechanisms of Action.

Berberine is an alkaloid from several medicinal plants originally used to treat diarrhea and dysentery as a traditional Chinese herbal medicine. In recent years, berberine has been discovered to exhibit a wide spectrum of biological activities in the treatment of diverse diseases ranging from cancer and neurological dysfunctions to metabolic disorders and heart diseases. This review article summarizes the clinical practice and laboratory exploration of berberine for the treatment of cardiometabolic and heart diseases, with a focus on the novel insights and recent advances of the underlying mechanisms recognized in the past decade. Berberine was found to display pleiotropic therapeutic effects against dyslipidemia, hyperglycemia, hypertension, arrhythmia, and heart failure. The mechanisms of berberine for the treatment of cardiometabolic disease involve combating inflammation and oxidative stress such as inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) activation, regulating electrical signals and ionic channels such as targeting human ether-a-go-go related gene (hERG) currents, promoting energy metabolism such as activating adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, modifying gut microbiota to promote transforming of berberine into its intestine-absorbable form, and interacting with non-coding RNAs via targeting multiple signaling pathways such as AMPK, mechanistic target of rapamycin (mTOR), etc. Collectively, berberine appears to be safe and well-tolerated in clinical practice, especially for those who are intolerant to statins. Knowledge from this field may pave the way for future development of more effective pharmaceutical approaches for managing cardiometabolic risk factors and preventing heart diseases.

Electrocatalytic Dehydrogenative Cyclization of 2-Vinylanilides for the Synthesis of Indoles.

Indole is prevalent in bioactive compounds and natural products. The development of efficient and sustainable methods to access this privileged structural scaffold has been a long-standing interest of synthetic chemists. Herein, we report an electrocatalytic method for the synthesis of indoles through dehydrogenative cyclization of 2-vinylanilides. The reactions employ an organic redox catalyst and do not require any external chemical oxidant, providing speedy and efficient access to 3-substituted and 2,3-disubstituted indoles.

Cardiac Rehabilitation with Targeted Intensity Improves Cardiopulmonary Functions Accompanying with Reduced Copeptin Level in Patients with Coronary Artery Disease.

Cardiac rehabilitation (CR) plays an important role in cardiovascular disease prevention. Understanding the key component of CR such as training intensity and biomarkers reflecting cardiopulmonary functions may help to better target the rehabilitation program. Thirty-four consecutive patients with coronary artery disease after percutaneous coronary intervention participated in the CR program. The difference between intervention group and control group was mainly the training intensity. Cardiopulmonary exercise testing (CPET) and blood biomarker measurements were performed before and after CR. The results demonstrated that it was safe and feasible to perform CR, while sufficient training intensity was required to significantly ameliorate CPET parameters. Among numerous biomarkers tested, vasopressin surrogate marker copeptin (CPP) improved significantly after CR. Moreover, improved CPP was correlated with exercise intensity and peak oxygen uptake, two most important indicators of cardiopulmonary exercise capacities. Therefore, CR may have a novel role in maintaining plasma osmolality and cardiovascular homeostasis. Graphical Abstract Cardiac rehabilitation training improves cardiopulmonary exercise parameters El and PVO2 which are correlated with reduced CPP level. CPP, copeptin; El, exercise intensity; POV2, peak oxygen uptake.

The potential value of Copeptin and Pentraxin3 for evaluating the severity of coronary stenosis in patients with coronary artery disease.

INTRODUCTION: Coronary artery disease (CAD) is an ischemic heart disease due to the narrowing of the coronary arteries resulting from atherosclerosis. Blood biomarkers have been well utilized for the diagnosis and prognosis of CAD. However, the value of biomarkers for evaluating coronary atherosclerosis remains to be clarified. This clinical investigation aimed to explore the potential value of biomarkers for evaluating the severity of coronary stenosis in CAD patients. METHODS: The extent of coronary atherosclerosis was accessed by the angiography-based quantitative measurement Gensini score (GS). Blood levels of Brain natriuretic peptide, Copeptin (CPP), Phosphodiesterase 9A, and Pentraxin3 (PTX3) were measured in 56 patients divided into three levels as low GS (n = 17), intermediate GS (n = 19) and high GS (n = 20) based on GS tertiles. RESULTS: We found that plasma concentrations of CPP and PTX3 were significantly elevated in patients with high GS compared with the low GS group. In addition, Pearson correlation analysis showed that CPP and PTX3 were positively correlated with the GS. Furthermore, Receiver operating characteristics analysis demonstrated that both CPP and PTX3 exhibited discriminative capacities for evaluating the extent of coronary stenosis. CONCLUSIONS: Laboratory tests of CPP and PTX3 via non-invasive means may provide novel information for risk stratification and disease management in CAD patients before invasive angiographic approaches. This study opens the door for enormous opportunities to explore new biomarkers with better efficiency, sensitivity and specificity as alternative/additional methods for evaluating the severity of coronary atherosclerosis in CAD patients in future research.