Buyang Huanwu Tang protects HO-induced RGC-5 cell against oxidative stress and apoptosis reactive oxygen species-mitogen-activated protein kinase signaling pathway.

OBJECTIVE: To study the molecular mechanism of Buyang Huanwu Tang() (BHT) protecting retinal ganglion cells (RGCs) from oxygen induced oxidative stress and apoptosis after anterior ischemia. METHODS: In this study, the Chinese herbs of BHT were extracted by first boiling in water, then were filtered, concentrated, and freeze-dried. The chemical profile of BHT extract was determined by liquid chromatography mass spectrometry (LC-MS). HO-induced RGC-5 cells were used as a cell model to investigate the protective effect and mechanism of BHT on RGCs. RESULTS: The survival rate of damaged RGC-5 by BHT was significantly increased by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazolium-romid method. Fluorescence activating cell sorter (FACS analysis) showed that BHT could significantly reduce apoptosis induced by oxidative stress the reactive oxygen species (ROS)-mitogen-activated protein kinase (MAPK)-Caspase-3 signal pathway. CONCLUSION: BHT possesses a high antioxidant capacity and could significantly reduce ROS levels of RGC-5 cells damaged by HO.Therefore, the present study has provided possible alternative strategies for the prevention and treatment of ischemic optic disease by using traditional Chinese herbal formulas.

Loss of RIP3 initiates annihilation of high-fat diet initialized nonalcoholic hepatosteatosis: A mechanism involving Toll-like receptor 4 and oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent and complex disease that confers a high risk of severe liver disorders. Although such public and clinical health importance, very few effective therapies are presently available for NAFLD. Here, we showed that receptor-interacting kinase-3 (RIP3) was up-regulated in liver of mouse with hepatic steatosis induced by high fat diet (HFD). After 16 weeks on a HFD, obesity, insulin resistance, metabolic syndrome, hepatic steatosis, inflammatory response and oxidative stress were significantly alleviated in liver of mice with the loss of RIP3. We provided mechanistic evidence that RIP3 knockdown attenuated hepatic dyslipidemia through preventing the expression of lipogenesis-associated genes. Furthermore, in the absence of RIP3, the transcription factor of nuclear factor-κB (NF-κB) signaling pathway activated by HFD was blocked, accompanied with the inhibition of NLRP3 inflammasome. We also found that RIP3 knockdown-induced activation of nuclear factor-erythroid 2 related factor 2/heme oxygenase-1 (Nrf-2/HO-1) led to the inhibition of oxidative stress. The detrimental effects of RIP3 on hepatic steatosis and related pathologies were confirmed in palmitate (PAL)-treated mouse liver cells. Of note, lipopolysaccharide (LPS)- or PAL-activated TLR-4 resulted in the up-regulation of RIP3 that was accompanied by the elevated inflammation and lipid deposition, and these effects were reversed in TLR-4 knockdown cells. Furthermore, promoting Nrf-2 pathway activation effectively reduced reactive oxygen species (ROS) generation and RIP3 expression in PAL-stimulated cells, consequently leading to the suppression of cellular inflammation and lipid accumulation. In contrast, blocking Nrf-2/HO-1 signaling abrogated RIP3 knockdown-reduced reactive oxygen species (ROS), inflammatory response and lipid deposition in PAL-stimulated cells. Taken together, the present study helped to elucidate how HFD-induced hepatic steatosis was regulated by RIP3, via the TLR-4/NF-κB and Nrf-2/HO-1 signaling pathways.

The vertical distributions of VOCs in the atmosphere of Beijing in autumn.

Volatile organic compounds (VOCs) in the air of Beijing City were measured at the heights of 8, 32, 140 and 280 m on the Beijing 325 m meteorological tower in autumn 2005. Concentrations of fifty-five compounds were determined by quantitative analytical methods. Our study utilized GC/MS analysis of 0.5 l air sample that were cryo-concentrated prior to analysis. The vertical distributions of VOCs were also investigated using 1-butene, isopentane, dichloromethane and toluene as representative compounds of several different categories. It is shown that 1-butene followed by 2-butene, isopentane followed by n-pentane, dichloromethane followed by chloroform and toluene followed by benzene are the most abundant compounds in the categories of alkene, alkane, halocarbon and aromatic hydrocarbon, respectively. The concentrations of TVOCs range from 51.2+/-39.7 ppb to 83.6+/-44.4 ppb on clear days, but from 62.9+/-19.0 ppb to 105.0+/-59.2 ppb on haze days. While alkenes and halocarbons contribute little to TVOCs, alkanes provide the largest percentage, ranging from about 46% to 63% at four different heights, which are followed by aromatic hydrocarbons ranging from about 15% to 27%. The vertical distributions of VOCs are complex. On clear days most distribution profiles show a decreasing trend with increasing height. On haze days, however, they exhibit first a decrease with increasing altitude from 8 m to 140 m and then a significant increase at 280 m. These results are understood by analyzing how the vertical distributions of VOCs are affected jointly by several factors such as meteorological parameters and transport property. In addition, principal components analysis (PCA) and cluster analysis show that VOCs have different origins at different heights.

iRhom2 loss alleviates renal injury in long-term PM2.5-exposed mice by suppression of inflammation and oxidative stress.

Particulate matter (PM2.5) is a risk factor for organ injury and disease progression, such as lung, brain and liver. However, its effects on renal injury and the underlying molecular mechanism have not been understood. The inactive rhomboid protein 2 (iRhom2), also known as rhomboid family member 2 (Rhbdf2), is a necessary modulator for shedding of tumor necrosis factor-α (TNF-α) in immune cells, and has been explored in the pathogenesis of chronic renal diseases. In the present study, we found that compared to the wild type (iRhom2+/+) mice, iRhom2 knockout (iRhom2-/-) protected PM2.5-exposed mice from developing severe renal injury, accompanied with improved renal pathological changes and functions. iRhom2-/- mice exhibited reduced inflammatory response, as evidenced by the reduction of interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α) and IL-18 in kidney samples, which might be, at least partly, through inactivating TNF-α converting enzyme/TNF-α receptors (TACE/TNFRs) and inhibitor of α/nuclear factor κ B (IκBα/NF-κB) signaling pathways. In addition, oxidative stress was also restrained by iRhom2-/- in kidney of PM2.5-exposed mice by enhancing heme oxygenase/nuclear factor erythroid 2-related factor 2 (HO-1/Nrf-2) expressions, and reducing phosphorylated c-Jun N-terminal kinase (JNK). In vitro, blockage of HO-1 or Nrf-2 rescued the inflammatory response and oxidative stress that were reduced by iRhom2 knockdown in PM2.5-incubated RAW264.7 cells. Similar results were observed in JNK activator-treated cells. Taken together, our findings indicated that iRhom2 played an essential role in regulating PM2.5-induced chronic renal damage, thus revealing a potential target for preventing chronic kidney diseases development.