Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction.

Myocardial apoptosis is a significant problem underlying ischemic heart disease. We previously reported significantly elevated expression of cytoplasmic Omi/HtrA2, triggers cardiomyocytes apoptosis. However, whether increased Omi/HtrA2 within mitochondria itself influences myocardial survival in vivo is unknown. We aim to observe the effects of mitochondria-specific, not cytoplasmic, Omi/HtrA2 on myocardial apoptosis and cardiac function. Transgenic mice overexpressing cardiac-specific mitochondrial Omi/HtrA2 were generated and they had increased myocardial apoptosis, decreased systolic and diastolic function, and decreased left ventricular remodeling. Transiently or stably overexpression of mitochondria Omi/HtrA2 in H9C2 cells enhance apoptosis as evidenced by elevated caspase-3, -9 activity and TUNEL staining, which was completely blocked by Ucf-101, a specific Omi/HtrA2 inhibitor. Mechanistic studies revealed mitochondrial Omi/HtrA2 overexpression degraded the mitochondrial anti-apoptotic protein HAX-1, an effect attenuated by Ucf-101. Additionally, transfected cells overexpressing mitochondrial Omi/HtrA2 were more sensitive to hypoxia and reoxygenation (H/R) induced apoptosis. Cyclosporine A (CsA), a mitochondrial permeability transition inhibitor, blocked translocation of Omi/HtrA2 from mitochondrial to cytoplasm, and protected transfected cells incompletely against H/R-induced caspase-3 activation. We report in vitro and in vivo overexpression of mitochondrial Omi/HtrA2 induces cardiac apoptosis and dysfunction. Thus, strategies to directly inhibit Omi/HtrA2 or its cytosolic translocation from mitochondria may protect against heart injury

Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds.

Previously, we only apply a traditional Chinese medicine (TCM) Danshen-Chuanxiong-Honghua (DCH) for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA) for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO). We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg) and FA (100 mg/kg) improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds

Sulfur-doped Nanographenes Containing Multiple Subhelicenes

In this work, we describe the synthesis and characterization of three novel sulfur-doped nanographenes (NGs) (1–3) containing multiple subhelicenes, including carbo[4]helicenes, thieno[4]helicenes, carbo[5]helicenes, and thieno[5]helicenes. Density functional theory calculations reveal that the helicene substructures in 1–3 possess dihedral angles from 15° to 34°. The optical energy gaps of 1–3 are estimated to be 2.67, 2.45, and 2.30 eV, respectively. These three sulfur-doped NGs show enlarged energy gaps compared to those of their pristine carbon analogues

Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β signaling and inhibition of the mitochondria-dependent apoptotic pathway.

Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and apoptosis were assessed by flow cytometry. Mitochondrial membrane potential (MMP) was determined by 5, 5\u27, 6, 6\u27-tetrachloro-1, 1\u27, 3, 3\u27-tetrathylbenzimidazol carbocyanine iodide (JC-1). Cytosolic translocation of mitochondrial cytochrome c and expression of caspase-9, caspase-3, Bcl-2 family proteins, and phosphorylated Akt and GSK-3β were determined by western blot. Pretreatment with GSRd (50 mg/kg) significantly augmented rat cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF) and ±dP/dt. GSRd reduced myocardial infarct size, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels after MI/R. In NRCs, GSRd (10 µM) inhibited SI/R-induced ROS generation (

Synthesis and Self-Assembly Behavior of Double Ullazine-Based Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic azomethine ylides (PAMY, 1) are versatile building blocks for the bottom-up synthesis of nitrogen-containing polycyclic aromatic hydrocarbons (N-PAHs). Although the chemistry of PAMY was already established few years ago, the cycloaddition of a double PAMY building block has not been reported so far. In this work, we demonstrate the first cycloaddition of a PAMY-dimer (6), which opens the access to three different alkyl ester-substituted N-PAHs with a laterally extended double ullazine scaffold (DU-1, DU-2 and DU-3). Interestingly, the cyclic voltammetry of DU-1-3 exhibited three reversible oxidation waves, which confirmed the electron-rich nature of the double ullazine scaffold. Furthermore, in-situ spectroelectrochemistry study of ethylhexyl ester-substituted DU-3 revealed the formation of different cationic species with new absorption bands up to 1689 nm. Additionally, the influence of the attached substituents on the film formation and supramolecular organization in the thin films were investigated by polarized optical microscopy and grazing incidence wide-angle X-ray scattering

Banxia Baizhu Tianma Decoction for Essential Hypertension: A Systematic Review of Randomized Controlled Trials

Objectives. To assess the current clinical evidence of Banxia Baizhu Tianma Decoction (BBTD) for essential hypertension (EH). Search Strategy. Electronic databases were searched until July 2012. Inclusion Criteria. We included randomized clinical trials testing BBTD against placebo, antihypertensive drugs, or combined with antihypertensive drugs against antihypertensive drugs. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Results. 16 randomized trials were included. Methodological quality of the included trials was evaluated as generally low. 2 trials compared prescriptions based on BBTD using alone with antihypertensive drugs. Meta-analysis showed no significant effect of modified BBTD compared with captopril in systolic blood pressure (MD: −0.75 (−5.77, 4.27); P=0.77) and diastolic blood pressure (MD: −0.75 (−2.89, 1.39); P=0.49). 14 trials compared the combination of BBTD or modified BBTD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed there are significant beneficial effect on systolic blood pressure in the combination group compare to the antihypertensive drugs (MD: −4.33 (−8.44, −0.22); P=0.04). The safety of BBTD is uncertain. Conclusions. There is encouraging evidence of BBTD for lowering SBP, but evidence remains weak. Rigorously designed trials are warranted to confirm these results

Risk factors on healthcare-associated infections among tuberculosis hospitalized patients in China from 2001 to 2020: A systematic review and meta-analysis

Background: China has been still suffering from high burden attributable to tuberculosis (TB) and healthcare-associated infections (HAIs). TB patients are at high risk to get HAIs. Evidence-based guidelines or regulations to constrain the rising HAIs among TB hospitalized patients are needed in China. The aim of this systematic review and meta-analysis is to investigate the risk factors associated with HAIs among TB hospitalized patients in Chinese hospitals. Methods: Medline, EMBASE and Chinese Journals Online databases were searched. The search was limited to studies published from January 1st 2001 to December 31st 2020. Meta-analyses of ORs of the risk factors between patients with HAIs and patients without HAIs among TB hospitalized patients were estimated. Heterogeneity among studies was assessed based on the τ ^ 2 and I2 statistics to select the meta-analysis model. Review Manager 5.3 was employed and P < 0.05 was considered as statistical significance. Results: 851 records were filtered from the databases, of which 11 studies were included in the quantitative meta-analysis. A total of 11,922TB patients were included in the systematic review and meta-analysis, of which 1133 were diagnosed as having HAIs. Age older than 60 years (OR: 2.89 [2.01–4.15]), complications (OR: 3.28 [2.10–5.13]), diabetes mellitus (OR: 1.63 [1.22–2.19]), invasive procedure (OR: 3.80 [2.25–6.42]), longer than 15 hospitalization days (OR: 2.09 [1.64–2.64]), secondary tuberculosis (OR: 2.25 [1.48–3.42]), smoking (OR: 1.40[1.02–1.93]), underlying disease (OR: 2.66 [1.53–4.62]), and use of antibiotics (OR: 2.77 [2.35–3.27]) were the main risk factors associated with HAIs among TB hospitalized patients with a statistical significance (P < 0.05). Conclusions: Age older than 60 years, presence of complications, presence of diabetes mellitus, invasive procedure, longer than 15 hospitalization days, secondary tuberculosis, smoking, presence of underlying disease, and use of antibiotics were the main risk factors which had a negative impact on HAIs among TB hospitalized patients in Chinese hospitals. These findings provided evidence for policy makers and hospital managers to make effective infection prevention and control measures to constrain the rising HAIs. It is also required that more cost-effective infection prevention and control measures should be widely applied in routinely medical treatment and clinical management to reduce the occurrence of HAIs among TB hospitalized patients

Helical Nanographenes Containing an Azulene Unit : Synthesis, Crystal Structures, and Properties

Three unprecedented helical nanographenes (1, 2, and 3) containing an azulene unit are synthesized. The resultant helical structures are unambiguously confirmed by X-ray crystallographic analysis. The embedded azulene unit in 2 possesses a record-high twisting degree (16.1°) as a result of the contiguous steric repulsion at the helical inner rim. Structural analysis in combination with theoretical calculations reveals that these helical nanographenes manifest a global aromatic structure, while the inner azulene unit exhibits weak antiaromatic character. Furthermore, UV/Vis-spectral measurements reveal that superhelicenes 2 and 3 possess narrow energy gaps (2: 1.88 eV; 3: 2.03 eV), as corroborated by cyclic voltammetry and supported by density functional theory (DFT) calculations. The stable oxidized and reduced states of 2 and 3 are characterized by in-situ EPR/Vis–NIR spectroelectrochemistry. Our study provides a novel synthetic strategy for helical nanographenes containing azulene units as well as their associated structures and physical properties. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Bioactive Peptides from Angelica sinensis

Since excessive reactive oxygen species (ROS) is known to be associated with aging and age-related diseases, strategies modulating ROS level and antioxidant defense systems may contribute to the delay of senescence. Here we show that the protein hydrolyzate from Angelica sinensis was capable of increasing oxidative survival of the model animal Caenorhabditis elegans intoxicated by paraquat. The hydrolyzate was then fractionated by ultrafiltration, and the antioxidant fraction (<3 kDa) was purified by gel filtration to obtain the antioxidant A. sinensis peptides (AsiPeps), which were mostly composed of peptides with <20 amino acid residues. Further studies demonstrate that AsiPeps were able to reduce the endogenous ROS level, increase the activities of the antioxidant enzymes superoxide dismutase and catalase, and decrease the content of the lipid peroxidation product malondialdehyde in nematodes treated with paraquat or undergoing senescence. AsiPeps were also shown to reduce age pigments accumulation and extend lifespan but did not affect the food-intake behavior of the nematodes. Taken together, our results demonstrate that A. sinensis peptides (AsiPeps) are able to delay aging process in C. elegans through antioxidant activities independent of dietary restriction

Electrochemically Exfoliated High-Quality 2H-MoS₂ for Multiflake Thin Film Flexible Biosensors

2D molybdenum disulfide (MoS₂) gives a new inspiration for the field of nanoelectronics, photovoltaics, and sensorics. However, the most common processing technology, e.g., liquid‐phase based scalable exfoliation used for device fabrication, leads to the number of shortcomings that impede their large area production and integration. Major challenges are associated with the small size and low concentration of MoS₂ flakes, as well as insufficient control over their physical properties, e.g., internal heterogeneity of the metallic and semiconducting phases. Here it is demonstrated that large semiconducting MoS₂ sheets (with dimensions up to 50 µm) can be obtained by a facile cathodic exfoliation approach in nonaqueous electrolyte. The synthetic process avoids surface oxidation thus preserving the MoS₂ sheets with intact crystalline structure. It is further demonstrated at the proof‐of‐concept level, a solution‐processed large area (60 × 60 µm) flexible Ebola biosensor, based on a MoS₂ thin film (6 µm thickness) fabricated via restacking of the multiple flakes on the polyimide substrate. The experimental results reveal a low detection limit (in femtomolar–picomolar range) of the fabricated sensor devices. The presented exfoliation method opens up new opportunities for fabrication of large arrays of multifunctional biomedical devices based on novel 2D materials