Evaluation of Ginsenoside Rg1 as a Potential Antioxidant for Preventing or Ameliorating Progression of Atherosclerosis

Purpose: To determine whether Rg1 inhibits H2O2-induced injury in human umbilical vein endothelial cells (HUVECs), an injury often regarded as a key early event in the development of atherosclerosis.Methods: Cell viability of HUVECs treated with Rg1 and/or H2O2 was measured using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide ( MTT) assay. Lactate dehydrogenase (LDH) release, lipid peroxidation, and reserved oxidase were detected using different available kits. The apoptosis pathway involved in the effect of Rg1 was also evaluated.Results: Exposing HUVECs to 100 μmol/L H2O2 significantly decreased cell viability (78.12 ± 1.78 %), nitric oxide production, and nitric oxide synthase, superoxide dismutase, and glutathione activities, but markedly increased malondialdehyde content (from 26.87 ± 3.97 to 45.84 ± 3.50 nmol/mg of protein) and LDH release (from 8.63 to 31.42 %) (p < 0.05). These results were accompanied by a decrease in mitochondrial membrane potential and up-regulation of Bid and caspase-3, -8, and -9 mRNA expressions. However, pretreatment with different Rg1 concentrations (4, 8, and 16 μmol/L) markedly attenuated these changes (p < 0.05).Conclusion: Rg1 may protect HUVECs against H2O2-induced injury via the anti-oxidative and antiapoptosis mechanisms, which could be applied potentially for the prevention of endothelial cell dysfunctions associated with atherosclerosis.Keywords: Ginsenoside Rg1; Human umbilical vein endothelium, Oxidative damage; Atherosclerosis

Anti-oxidative Effect of Ligustrazine on Treatment and Prevention of Atherosclerosis

Purpose: To investigate the protective effects of ligustrazine on oxidative stress-induced atherosclerosis.Methods: The indicators related to oxidative stress were determined using commercially available assay kits. MTT assay was used to assess the survival rate of human umbilical vein endothelial cells (HUVECs). HUVECs apoptosis was analyzed using fluorescence staining and flow cytometry. mRNA expression level and activity of caspases 3, 8, and 9 were determined via quantitative real-time polymerase chain reaction (PCR) and caspase 3, 8, and 9 assay kits.Results: Ligustrazine concentration of < 80 μmol/L had negligible inhibitory effect on HUVECs viability and protected HUVECs against oxygen stress damage by regulating the indicators related to oxidative stress. Flow cytometry results show that ligustrazine ameliorated H2O2-induced apoptosis, while the proportion of cells that stepped into early apoptosis and late apoptosis or necrosis were 52.7 and 0.6 %, respectively, in the H2O2 group, and 38.2 and 1.3 %, respectively, in the ligustrazine group. In addition, ligustrazine attenuated the up-regulation of caspase 3, 8, and 9 mRNA expression levels and activity.Conclusion: Ligustrazine can protect HUVECs against H2O2-induced injuries by regulating the indicators related to oxidative stress and suppressing the overexpression of caspases 3, 8, and 9. The protective mechanism of ligustrazine on H2O2-induced injury in HUVECs may be a caspase-dependent anti-apoptotic mechanism which provide important information for treating and preventing oxidative stress-induced atherosclerosis.Keywords: Ligustrazine, Oxidative stress, Umbilical vein, Endothelial cells, Atherosclerosi

Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.BACKGROUND AND AIMS: Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. METHODS: Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non-sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. RESULTS: A total of 460 980 and 14 462 patients were identified for the non-sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference -0.04 mmHg (95% confidence interval -0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. CONCLUSIONS: This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

Background Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased and Aims blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Methods Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. Results A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. Conclusions This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice

Candida albicans repetitive elements display epigenetic diversity and plasticity

Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Quantum Transduction of Telecommunications-band Single Photons from a Quantum Dot by Frequency Upconversion

The ability to transduce non-classical states of light from one wavelength to another is a requirement for integrating disparate quantum systems that take advantage of telecommunications-band photons for optical fiber transmission of quantum information and near-visible, stationary systems for manipulation and storage. In addition, transducing a single-photon source at 1.3 {\mu}m to visible wavelengths for detection would be integral to linear optical quantum computation due to the challenges of detection in the near-infrared. Recently, transduction at single-photon power levels has been accomplished through frequency upconversion, but it has yet to be demonstrated for a true single-photon source. Here, we transduce the triggered single-photon emission of a semiconductor quantum dot at 1.3 {\mu}m to 710 nm with a total detection (internal conversion) efficiency of 21% (75%). We demonstrate that the 710 nm signal maintains the quantum character of the 1.3 {\mu}m signal, yielding a photon anti-bunched second-order intensity correlation, g^(2)(t), that shows the optical field is composed of single photons with g^(2)(0) = 0.165 < 0.5.Comment: 7 pages, 4 figure

Objective effect manifestation of pectus excavatum on load-stressed pulmonary function testing: a case report

Abstract Introduction Pectus excavatum is the most common congenital deformity of the anterior chest wall that, under certain conditions, may pose functional problems due to cardiopulmonary compromise and exercise intolerance. Case presentation We present the case of an otherwise physically-adept 21-year-old Chinese sportsman with idiopathic pectus excavatum, whose symptoms manifested only on bearing a loaded body vest and backpack during physical exercise. Corroborative objective evidence was obtained via load-stressed pulmonary function testing, which demonstrated restrictive lung function. Conclusion This report highlights the possible detrimental synergism of thoracic load stress and pectus excavatum on cardiopulmonary function. Thoracic load-stressed pulmonary function testing provides objective evidence in support of such a synergistic relationship.</p