Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC–Q–TOF–MS/MS

A rapid and sensitive UPLC/Q–TOF–MS method has been established for analysis of the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi (FTZ) capsule, an effective compound prescription for treating hyperlipidemia in the clinic. The UPLC/MS information of samples was obtained first in FTZ preparation and FTZ-treated rat serum. Mass spectra were acquired in both negative and positive ion modes. Thirty-six constituents in rat serum after oral administration of FTZ were detected, including the alkaloids, ginsenosides, pentacyclic triterpenes, and their metabolites. These chemicals were identified based on the retention time and mass spectrometry data with those of authentic standards or comparison of the literatures reports. Twenty-seven prototype components originated from FTZ and nine were the metabolites of the FTZ constituents. These results shed light on the potential active constituents of the complex traditional Chinese medicinal formulas

Ginsenoside Rb1 ameliorates the abnormal hepatic glucose metabolism by activating STAT3 in T2DM mice

Ginsenoside Rb1, a major bioactive component of Panax ginseng C. A. Mey., exerts beneficial effects on type 2 diabetes mellitus (T2DM), but its underlying mechanism is unclear. STAT3 is a key factor regulating energy metabolism. Herein, we tested whether Rb1 regulates STAT3-controlled hepatic glucose metabolism to ameliorate T2DM. Rb1 ameliorated abnormal hepatic glucose metabolism, insulin resistance, and liver steatosis in T2DM mice. Hepatic STAT3 phosphorylation was decreased in T2DM and increased after Rb1 treatment. Moreover, Rb1 reversed the decreased expressions of glycolytic enzymes and the increased expressions of gluconeogenic enzymes in T2DM. STAT3 activation increased the expressions of glycolytic enzymes and decreased the expressions of gluconeogenic enzymes in vitro, and vice versa. Further, STAT3 inhibition reversed the changes of these enzymes induced by Rb1 in insulin-resistant cells. Taken together, Rb1 ameliorated abnormal hepatic glucose metabolism in T2DM in a STAT3-dependent manner, which provides experimental bases for Rb1 in treating T2DM

Wintertime nitrate formation during haze days in the Guanzhong basin, China: A case study

In this study, the formation of nitrate aerosol from 16 to 24 December 2015 in the Guanzhong basin, China is simulated using the WRF-Chem model. The predicted near-surface O-3, NO2, and fine particulate matters (PM2.5) in the basin and inorganic aerosols and nitrous acid (HONO) in Xi'an are generally in good agreement with the observations. Sensitivity studies show that the heterogeneous HONO sources play an appreciable role in the nitrate formation in the basin, contributing 9.2% of nitrate mass concentrations during heavy haze days. Nitrate formation is also affected by sulfate due to their competition for ammonia, particularly in urban areas. A 50% decrease in SO2 emissions enhances the nitrate concentration by 6.2% during heavy haze days on average in the basin, and a 50% increase in SO2 emission reduces the nitrate concentration by 9.7%. The roles of HONO and sulfate competition in nitrate formation are strongly modulated by ammonia. Agricultural emissions predominate the nitrate level in the basin (93.5%), but the non-agricultural sources cannot substantially influence nitrate formation (3.7%-14.6%). Reducing agricultural emission is an effective control strategy to mitigate nitrate pollution in the basin. (C) 2018 Elsevier Ltd. All rights reserved

Neuroprotective effects of a standardized flavonoid extract from diospyros kaki leaves

Ethnopharmacological relevance: Flavonoids, extracted from the leaves of Diospyros kaki, are the main therapeutic components of NaoXingQing (NXQ), a potent and patented Chinese herbal remedy widely used in China for the treatment of apoplexy syndrome. Aim of the study: To investigate the neuroprotective effects of FLDK-P70, a standardized flavonoid extract, using in vivo rat models of both focal ischemia/reperfusion (I/R) injury induced by middle cerebral artery occlusion (MCAO) and on transient global brain ischemia induced by four-vessel occlusion (4-VO). We also aim to examine the effects of FLDK-P70 on glutamate-induced cell injury of hippocampal neurons as well as on hypoxia-induced injury of cortical neurons in primary cell culture. Materials and methods and results: Administration of FLDK-P70 for 12 days (40, 80 mg/kg body weight, p.o., 5 days before and 7 days after 4-VO) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. Similarly, administration of FLDK-P70 for 7 days (40, 80 mg/kg body weight, p.o., 3 days before and 4 days after MCAO) significantly reduced the lesion of the insulted brain hemisphere and improved the neurological behavior of rats. In primary rat hippocampal neuronal cultures, pretreatment with FLDK-P70 (5, 10 g/ml) protected neurons from glutamate-induced excitotoxic neuronal death in a dose-dependent manner. In primary rat cerebral cortical neuronal culture, pretreatment with FLDK-P70 (25, 100 g/ml) also reduced hypoxia-reoxygen induced neuronal death and apoptosis in a dose-dependent manner. Conclusions: These in vivo and in vitro results suggest that FLDK-P70 significantly protects rats fromMCAO and 4-VO ischemic injury in vivo and protects hippocampal neurons from glutamate-induced excitotoxic injury as well as cortical neurons from hypoxia-induced injury in vitro. The mechanisms of these effects may be due to the antioxidative activity of the flavonoids. These results convincingly demonstrate that FLDK-P70 may be useful for the prevention and treatment of ischemia/reperfusion injury and other related neurodegenerative diseases.No Full Tex

Secondary organic aerosol enhanced by increasing atmospheric oxidizing capacity in Beijing-Tianjin-Hebei (BTH), China

The implementation of the Air Pollution Prevention and Control Action Plan in China since 2013 has profoundly altered the ambient pollutants in the Beijing-Tianjin-Hebei (BTH) region. Here we show observations of substantially increased O-3 concentrations (about 30 %) and a remarkable increase in the ratio of organic carbon (OC) to elemental carbon (EC) in BTH during the autumn from 2013 to 2015, revealing an enhancement in atmospheric oxidizing capacity (AOC) and secondary organic aerosol (SOA) formation. To explore the impacts of increasing AOC on the SOA formation, a severe air pollution episode from 3 to 8 October 2015 with high O-3 and PM2.5 concentrations is simulated using the WRF-Chem model. The model performs reasonably well in simulating the spatial distributions of PM2.5 and O-3 concentrations over BTH and the temporal variations in PM2.5, O-3, NO2, OC, and EC concentrations in Beijing compared to measurements. Sensitivity studies show that the change in AOC substantially influences the SOA formation in BTH. A sensitivity case characterized by a 31 % 03 decrease (or 36 % OH decrease) reduces the SOA level by about 30 % and the SOA fraction in total organic aerosol by 17 % (from 0.52 to 0.43, dimensionless). Spatially, the SOA decrease caused by reduced AOC is ubiquitous in BTH, but the spatial relationship between SOA concentrations and the AOC is dependent on the SOA precursor distribution. Studies on SOA formation pathways further show that when the AOC is reduced, the SOA from oxidation and partitioning of semivolatile primary organic aerosol (POA) and coemitted intermediate volatile organic compounds (IVOCs) decreases remarkably, followed by those from anthropogenic and biogenic volatile organic compounds (VOCs). Meanwhile, the SOA decrease in the irreversible uptake of glyoxal and methylglyoxal on the aerosol surfaces is negligible.</p

The traditional Chinese medicine formula Fufang-Zhenzhu-Tiaozhi protects myocardia from injury in diabetic minipigs with coronary heart disease

Background and purpose: Diabetes mellitus (DM) is a major risk factor for coronary heart disease (CHD). Previous research has reported that the Fufang-Zhenzhu-Tiaozhi (FTZ) formula has obvious effects on the treatment of dyslipidemia and hyperglycemia. In the present study, we intended to establish a convenient DM-CHD model in minipigs and investigated the protective effect of FTZ against myocardial injury and its mechanism. Methods: The DM-CHD model was established by a high-fat/high-sucrose/high-cholesterol diet (HFSCD) combined with balloon injury in the coronary artery. Subsequently, sixteen Wuzhishan minipigs were assigned to three groups: control group, model group, and FTZ group. The model group and FTZ group were given a HFSCD, while the control group was given a normal diet (ND). FTZ was given with meals in the FTZ group. During this time, biochemical parameters, such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL-C), and fasting blood glucose (FBG), were measured by using testing kits. Insulin (INS) was determined by ELISA, and the homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance levels. After FTZ administration, the plasma levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) were measured by using ELISA kits to evaluate myocardial injury. Coronary artery stenosis was analyzed by angiographic and HE staining. Myocardial ischemia was assayed with electrocardiogram (ECG). Moreover, cytokines, including interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), and tumor necrosis factor-alpha (TNF-α), were measured by ELISA kits to assess inflammation. The myocardial tissue was collected, and the pathological morphology was observed by transmission electron microscopy (TEM), HE staining, and Masson staining. Western blots were used to detect the expression of PI3K, AKT, p-AKT, p-NF-κB, and NF-κB. Results: A DM-CHD model in minipigs with glucose-lipid metabolism disorder, coronary artery incrassation and myocardial damage was successfully established through balloon injury in the coronary artery combined with HFSCD. FTZ effectively inhibited coronary artery incrassation and protected the myocardium against injury in DM-CHD minipigs. FTZ decreased proinflammatory cytokine levels and upregulated the protein expression of the PI3K/Akt pathway in the myocardium. Conclusions: A novel DM-CHD model in minipigs was successfully established through balloon injury in the coronary artery combined with HFSCD. FTZ has a protective effect against myocardial injury in DM-CHD by inhibiting inflammation and activating the PI3K/AKT signaling pathway

A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML

Summertime ozone formation in Xi'an and surrounding areas, China

In this study, the ozone (O-3) formation in China&#39;s northwest city of Xi&#39;an and surrounding areas is investigated using the Weather Research and Forecasting atmospheric chemistry (WRF-Chem) model during the period from 22 to 24 August 2013, corresponding to a heavy air pollution episode with high concentrations of O-3 and PM2.5. The model generally performs well compared to measurements in simulating the surface temperature, relative humidity, and wind speed and direction, near-surface O-3 and PM2.5 mass concentrations, and aerosol constituents. High aerosol concentrations in Xi&#39;an and surrounding areas significantly decrease the photolysis frequencies and can reduce O-3 concentrations by more than 50 mu g m(-3) (around 25 ppb) on average. Sensitivity studies show that the O-3 production regime in Xi&#39;an and surrounding areas is complicated, varying from NOx to VOC (volatile organic compound)-sensitive chemistry. The industrial emissions contribute the most to the O-3 concentrations compared to biogenic and other anthropogenic sources, but neither individual anthropogenic emission nor biogenic emission plays a dominant role in the O-3 formation. Under high O-3 and PM2.5 concentrations, a 50 % reduction in all the anthropogenic emissions only decreases near-surface O-3 concentrations by about 14 % during daytime. The complicated O-3 production regime and high aerosol levels pose a challenge for O-3 control strategies in Xi&#39;an and surrounding areas. Further investigation regarding O-3 control strategies will need to be performed, taking into consideration the rapid changes in anthropogenic emissions that are not reflected in the current emission inventories and the uncertainties in the meteorological field simulations