4-[2-(Hydrogen phosphonato)-2-hydroxy-2-phosphonoethyl]pyridinium

The title compound, C7H11NO7P2, exists as a zwitterion in which the positive charge resides on the protonated pyridyl N atom and the negative charge on one of the two phosphate groups. In the crystal, adjacent molcules are linked by O—H⋯O and N—H⋯O hydrogen bonds into a three-dimensional network

Systemic adiponectin malfunction as a risk factor for cardiovascular disease.

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad\u27s metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad\u27s anti-inflammatory and anti-ischemic (resulting in cardioprotective) effects have also been discovered. Since its 1995 discovery, Ad has garnered considerable attention for its role in diabetic and cardiovascular pathology. Clinical observations have demonstrated the association of hypoadiponectinemia in patients with obesity, cardiovascular disease, and insulin resistance. In this review, we elaborate currently known information about Ad malfunction and deficiency pertaining to cardiovascular disease risk (including atherosclerosis, endothelial dysfunction, and cardiac injury), as well as review evidence supporting Ad resistance as a novel risk factor for cardiovascular injury, providing insight about the future of Ad research and the protein\u27s potential therapeutic benefits

Modified Glucose-Insulin-Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery

Background Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin-glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double-blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in-hospital major adverse cardiac events including all-cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate-1 and protein kinase B in the hearts of GIK-treated patients. Systemic blood lactate was also reduced in GIK-treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in-hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT01516138

Assessment of mitochondrial dysfunction and implications in cardiovascular disorders

Mitochondria play a pivotal role in cellular function, not only acting as the powerhouse of the cell, but also regulating ATP synthesis, reactive oxygen species (ROS) production, intracellular Ca2+ cycling, and apoptosis. During the past decade, extensive progress has been made in the technology to assess mitochondrial functions and accumulating evidences have shown that mitochondrial dysfunction is a key pathophysiological mechanism for many diseases including cardiovascular disorders, such as ischemic heart disease, cardiomyopathy, hypertension, atherosclerosis, and hemorrhagic shock. The advances in methodology have been accelerating our understanding of mitochondrial molecular structure and function, biogenesis and ROS and energy production, which facilitates new drug target identification and therapeutic strategy development for mitochondrial dysfunction-related disorders. This review will focus on the assessment of methodologies currently used for mitochondrial research and discuss their advantages, limitations and the implications of mitochondrial dysfunction in cardiovascular disorders

In vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth

Purpose: To investigate the in vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth of Sichuan Province, China. Methods: The total flavonoids of Elsholtzia densa Bent were extracted utilizing the ultrasonic extraction method, and purified by D101 macroporous adsorption resin. An in vitro antioxidant test, 3-(4,5dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and iCELLigence system were used to evaluate their antioxidant, antibacterial and anti-tumor activities. Results: The results showed that the total flavonoids exhibited good scavenging ability in hydroxyl radical (•OH), DPPH free radical (DPPH•), and super oxide anion radical (O2-•). Antioxidant activity was higher than for control (ascorbic acid). Their antibacterial activity was good with minimum inhibitory concentration (MIC) of 2, 4 and 14 μg/mL against Escherichia coli, Staphylococcus aureus and Bacillus subtilis, respectively. Anti-proliferation data from the iCELLigence system studies showed that the total flavonoids significantly inhibited the growth of five types of cells, including a normal human hepatocytes cell line (L02), two human hepatocellular carcinoma cell line (SMMC-7721 and HepG-2), a human cervical cancer cell line (Hela) and a Baby Hamster Syrian Kidney cell line (BHK-21) (p < 0.05). AO/EB staining indicate that the total flavonoids might cause apoptosis of Hela cells. Conclusion: The results suggest that the total flavonoids from Elsholtzia densa Bent are potential natural antioxidants and antimicrobial agent, with anti-cancer properties. Keywords: Elsholtzia densa Benth., Total flavonoids, Antioxidant activity, Antibacterial activity, Antitumor activit

Lusin-type approximation of Sobolev by Lipschitz functions, in Gaussian and RCD(K,∞)RCD(K,\infty) spaces

We establish new approximation results, in the sense of Lusin, of Sobolev functions by Lipschitz ones, in some classes of non-doubling metric measure structures. Our proof technique relies upon estimates for heat semigroups and applies to Gaussian and $RCD(K, \infty)$ spaces. As a consequence, we obtain quantitative stability for regular Lagrangian flows in Gaussian settings