142 research outputs found
Notoginsenoside R1 attenuates high glucose-induced endothelial damage in rat retinal capillary endothelial cells by modulating the intracellular redox state
No full textChunlan Fan, Yuan Qiao, Minke Tang Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China Abstract: The aim of this study was to examine whether Notoginsenoside R1 (NR1) attenuates high glucose-induced cell damage in rat retinal capillary endothelial cells (RCECs) and to explore the mechanisms involved. The exposure of rat RCECs to high concentration of glucose (30 mM) for 72 h led to significant cytotoxicity, including decreased cell viability, reduced mitochondrial DNA copy number, increased lactate dehydrogenase release and elevated apoptosis. NR1, when present in the culture medium, markedly attenuated the high glucose-induced cytotoxicity in rat RCECs. Moreover, high glucose also induced a significant increase in intracellular reactive oxygen species and subsequently increased the activity of NADPH oxidase and poly-ADP (ribose) polymerase, whereas the activity of catalase decreased. The addition of NR1 to the medium significantly reduced the generation of reactive oxygen species, inhibited NADPH oxidase and poly-ADP (ribose) polymerase activities and increased catalase activity in RCECs, accompanied by a reduced cellular nitrotyrosine level. To explore the underlying mechanisms involved, the cellular redox status was monitored. Both the cellular NAD+ and NADPH levels decreased significantly in high glucose medium, which resulted in a marked decrease in the NAD+/NADH and NADPH/NADP+ ratios. High glucose stimulation also enhanced the accumulation of GSSG, maintaining the GSH/GSSG ratio lower than that in the control group with 5.5 mM glucose. When treated with NR1, the cellular NAD+, NADPH and GSH concentrations increased, and the ratios of NAD+/NADH, NADPH/NADP+ and GSH/GSSG increased, similar to the control group. These results demonstrate that NR1 attenuates high glucose-induced cell damage in RCECs. Therefore, NR1 may exert its protective effects via mechanisms that involve changes in the cellular redox state. Keywords: Notoginsenoside R1, high glucose, retinal capillary endothelial cells, apoptosis, reactive oxygen species, NADP
Iridium-Catalyzed Diastereo- and Enantioselective [4 + 1] Cycloaddition of Hydroxyallyl Anilines with Sulfoxonium Ylides
No full textWe present here an iridium-catalyzed diastereo- and enantioselective
[4 + 1] cycloaddition reaction of hydroxyallyl anilines with sulfoxonium
ylides under mild reaction conditions, leading to 3-vinyl indolines
in moderate to good yields with excellent enantioselectivities. Control
experiments disclosed a plausible reaction mechanism
Unraveling the link between heavy metals, perfluoroalkyl substances and depression: Insights from epidemiological and bioinformatics strategies
No full textHeavy metals and per- and polyfluoroalkyl substances (PFASs) have become particularly important when studying the development of depression, a common illness that severely restricts psychosocial functioning and diminishes quality of life. Therefore, the potential joint effects of heavy metal and PFAS exposure on depression, as well as the underlying mechanisms involved, were investigated by using integrated epidemiological and bioinformatic approaches in the present study. A thorough analysis of 7301 samples from the National Health and Nutrition Examination Survey (NHANES) cycles that occurred between 2005 and 2018 was performed. Single-exposure studies have shown that cadmium exposure is positively associated with depression, whereas perfluorooctanesulfonic acid (PFOS) exposure and perfluorodecanoic acid (PFDE) exposure are negatively associated with depression. Furthermore, the Bayesian kernel machine regression (BKMR) and quantile g-computation (QGcomp) models were employed to investigate the collective impact of exposure to mixed metals on depression. Cadmium emerged as the principal contributor to depression. Moreover, the addition of PFAS to the metal mixture had an antagonistic effect on depression, with PFOS having the most prominent influence. Analysis of the effects of co-exposure to cadmium and PFOS confirmed the presence of an antagonistic effect. The inflection points of cadmium and PFOS were determined to be −1.11 and 2.27, respectively. Additionally, exposure to cadmium and PFOS had the opposite effects on two crucial pathways, namely, the rap1 and calcium signaling pathways, which involve core genes related to depression such as ADORA2A, FGF2, and FGFR1. These findings have significant implications for future studies and provide new strategies for exploring the mechanisms underlying co-exposure effects
Notoginsenoside R1 attenuates high glucose-induced endothelial damage in rat retinal capillary endothelial cells by modulating the intracellular redox state
No full textAdvances of DNA Damage Repair and Cisplatin Resistance Mechanisms in Lung Cancer
No full textLung cancer is the most common cause of death from cancer worldwide per year. Platinum-based combination chemotherapy is a main treatment of lung cancer. Cisplatin is adopted widely and used effectively in the first-line chemotherapy. Unfortunately, development of cisplatin resistance is a major obstacle to the success of lung caner. Cisplatin is a cell-cycle-non-specific cytotoxic drugs and its main target is DNA. Thus, defective DNA damage repair is one of the main mechanisms of cisplatin resistance. In this review, we will focus on the defective DNA damage repair in cisplatin resistance of lung cancer including nucleotide excision repair, DNA mismatch repair, DNA double-strand break repair and translesion synthesis
Steganalysis of compressed speech to detect covert voice over Internet protocol channels
No full textA network covert channel is a passage along which information leaks across the network in violation of security policy in a completely undetectable manner. This study reveals our findings in analysing the principle of G.723.1 codec that there are `unused' bits in G.723.1 encoded audio frames, which can be used to embed secret messages. A novel steganalysis method that employs the second detection and regression analysis is suggested in this study. The proposed method can not only detect the hidden message embedded in a compressed voice over Internet protocol (VoIP) speech, but also accurately estimate the embedded message length. The method is based on the second statistics, that is, doing a second steganography (embedding information in a sampled speech at an embedding rate followed by embedding another information at a different level of data embedding) in order to estimate the hidden message length. Experimental results have proven the effectiveness of the steganalysis method for detecting the covert channel in the compressed VoIP speech
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