Preparation of ß-galacto-oligosaccharides using a novel endo-1,4-ß-galactanase from Penicillium oxalicum.

Endo-1,4-ß-galactanase is an indispensable tool for preparing prebiotic ß-galacto-oligosaccharides (ß-GOS) from pectic galactan resources. In the present study, a novel endo-1,4-ß-galactanase (PoßGal53) belonging to glycoside hydrolase family 53 from Penicillium oxalicum sp. 68 was cloned and expressed in Pichia pastoris GS115. Upon purification by affinity chromatography, recombinant PoßGal53 exhibited a single band on SDS-PAGE with a molecular weight of 45.0 kDa. Using potato galactan as substrate, PoßGal53 showed optimal reaction conditions of pH 4.0, 40 °C, and was thermostable, retaining >80 % activity after incubating below 45 °C for 12 h. Significantly, PoßGal53 exhibited relatively conserved substrate specificity for (1 â†’ 4)-ß-D-galactan with an activity of 6244 ± 282 U/mg. In this regard, the enzyme is in effect the most efficient endo-1,4-ß-galactanase identified to date. By using PoßGal53, ß-GOS monomers were prepared from potato galactan and separated using medium pressure liquid chromatography. HPAEC-PAD, MALDI-TOF-MS and ESI-MS/MS analyses demonstrated that these ß-GOS species ranged from 1,4-ß-D-galactobiose to 1,4-ß-D-galactooctaose (DP 2-8) with high purity. This work provides not only a highly active tool for enzymatic degradation of pectic galactan, but an efficient protocol for preparing ß-GOS.

Geniposide ameliorates atherosclerosis by regulating macrophage polarization via perivascular adipocyte-derived CXCL14.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis. AIM OF THE STUDY: To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage polarization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT). MATERIALS AND METHODS: ApoE-/- mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays. RESULTS: The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE-/- mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geniposide increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells. CONCLUSION: In summary, our findings suggest that geniposide protects ApoE-/- mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment.

Dingxin recipe â ¢ ameliorates hyperlipidemia injury in SD rats by improving the gut barrier, particularly the SCFAs/GPR43 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. AIM OF THE STUDY: Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR Ⅲ in hyperlipidemia. MATERIALS AND METHODS: The bioactive compounds of DXR Ⅲ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR Ⅲ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. RESULTS: DXR Ⅲ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR Ⅲ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR Ⅲ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR Ⅲ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR Ⅲ and SCFAs upregulated the expression of colon ABCA1. CONCLUSION: DXR Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.

Co-occurrence of aflatoxins in plant oil products from China.

Aflatoxins have been detected as contaminants of oil crops before harvesting and drying, during storage and manufacturing and could be transferable to plant oils. There are more than 20 different types of aflatoxins, among which the most commonly occurring are the B1, B2, G1 and G2. Concentrations of these four aflatoxins were determined in plant oils from retail shops in China and in crude peanut oil extracted from culled mouldy peanuts by HPLC with fluorescence detection. Overall, aflatoxins were present in 25 of the 63 samples. The four aflatoxins co-existed in vegetable oil, but the content of AFB1 was usually higher than the other aflatoxins. Particularly in the case of highly contaminated oil samples, AFB1 accounted for 68% of the total aflatoxins. According to the health risk assessment, the low margin of exposure values from AFB1 in oils suggests a high level of concern for children.

Dietary Bacillus licheniformis improves the effect of Astragalus membranaceus extract on blood glucose by regulating antioxidation activity and intestinal microbiota in InR[E19]/TM2 Drosophila melanogaster.

BACKGROUND: The diabetes mellitus prevalence is rapidly increasing in most parts of the world and has become a vital health problem. Probiotic and herbal foods are valuable in the treatment of diabetes. METHODS AND PERFORMANCE: In this study, Bacillus licheniformis (BL) and Astragalus membranaceus extract (AE) were given with food to InR[E19]/TM2 Drosophila melanogaster, and the blood glucose, antioxidation activity and intestinal microbiota were investigated. The obtained results showed that BA (BL and AE combination) supplementation markedly decreased the blood glucose concentration compared with the standard diet control group, accompanied by significantly increased enzymatic activities of catalase (CAT), decreased MDA levels and prolonged lifespan of InR[E19]/TM2 D. melanogaster. The treatments with BL, AE and BA also ameliorated intestinal microbiota equilibrium by increasing the population of Lactobacillus and significantly decreasing the abundance of Wolbachia. In addition, clearly different evolutionary clusters were found among the control, BL, AE and BA-supplemented diets, and the beneficial microbiota, Lactobacillaceae and Acetobacter, were found to be significantly increased in male flies that were fed BA. These results indicated that dietary supplementation with AE combined with BL not only decreased blood glucose but also extended the lifespan, with CAT increasing, MDA decreasing, and intestinal microbiota improving in InR[E19]/TM2 D. melanogaster. CONCLUSION: The obtained results showed that dietary supplementation with BL and AE, under the synergistic effect of BL and AE, not only prolonged the lifespan of InR[E19]/TM2 D. melanogaster, increased body weight, and improved the body's antiaging enzyme activity but also effectively improved the types and quantities of beneficial bacteria in the intestinal flora of InR[E19]/TM2 D. melanogaster to improve the characteristics of diabetes symptoms. This study provides scientific evidence for a safe and effective dietary therapeutic method for diabetes mellitus.

Advanced applications of mass spectrometry imaging technology in quality control and safety assessments of traditional Chinese medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCMs) have made great contributions to the prevention and treatment of human diseases in China, and especially in cases of COVID-19. However, due to quality problems, the lack of standards, and the diversity of dosage forms, adverse reactions to TCMs often occur. Moreover, the composition of TCMs makes them extremely challenging to extract and isolate, complicating studies of toxicity mechanisms. AIM OF THE REVIEW: The aim of this paper is therefore to summarize the advanced applications of mass spectrometry imaging (MSI) technology in the quality control, safety evaluations, and determination of toxicity mechanisms of TCMs. MATERIALS AND METHODS: Relevant studies from the literature have been collected from scientific databases, such as "PubMed", "Scifinder", "Elsevier", "Google Scholar" using the keywords "MSI", "traditional Chinese medicines", "quality control", "metabolomics", and "mechanism". RESULTS: MSI is a new analytical imaging technology that can detect and image the metabolic changes of multiple components of TCMs in plants and animals in a high throughput manner. Compared to other chemical analysis methods, such as liquid chromatography-mass spectrometry (LC-MS), this method does not require the complex extraction and separation of TCMs, and is fast, has high sensitivity, is label-free, and can be performed in high-throughput. Combined with chemometrics methods, MSI can be quickly and easily used for quality screening of TCMs. In addition, this technology can be used to further focus on potential biomarkers and explore the therapeutic/toxic mechanisms of TCMs. CONCLUSIONS: As a new type of analysis method, MSI has unique advantages to metabolic analysis, quality control, and mechanisms of action explorations of TCMs, and contributes to the establishment of quality standards to explore the safety and toxicology of TCMs.

The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota.

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.

Dingxin Recipe IV attenuates atherosclerosis by regulating lipid metabolism through LXR-α/SREBP1 pathway and modulating the gut microbiota in ApoE-/- mice fed with HFD.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear. AIM OF THE STUDY: This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice. MATERIALS AND METHODS: 40 male ApoE-/- mice were fed on HFD for 12 weeks and were then treated with DXR IV (1.8, 0.9, or 0.45 g/kg/d) for another 12 weeks. The decroation of DXR IV contains four traditional Chinese medicines: the dried rhizome of Coptis chinensis Franch. (15.09%), the root of Salvia miltiorrhiza Bunge (28.30%), the seed of Ziziphus jujuba Mill. (37.74%) and the fruiting body of Ganoderma lucidum (Leyss.ex Fr.) Karst. (18.87%). 8 male c57BL/6 mice fed a normal diet served as control group. The atherosclerotic plaque was quantified by oil-red O staining and masson trichrome staining. Mice feces were collected. The gut micobiota were detected by 16S rRNA gene sequencing and fecal metabolites were analyzed by 1H NMR spectroscopy. The effect of DXR IV on blood lipids (TG, TC, LDL-C, HDL-C) was investigated. The lipid metabolism related genes were determined by RT-qPCR and western blotting respectively. RESULTS: DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-α and SREBP1 decreased significantly in DXR IV group while LXR-ß, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-α/SREBP1 but not LXRß and SREBP2. CONCLUSIONS: DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage.

Integrated Care for Older People Screening Tool for Measuring Intrinsic Capacity: Preliminary Findings From ICOPE Pilot in China.

Objectives: The World Health Organization (WHO) proposed the Integrated Care for Older People (ICOPE) screening tool to identify older people with priority conditions associated with declines in intrinsic capacity (IC). We aimed to determine the clinical utility of the WHO ICOPE screening tool in a Chinese population. Method: A total of 376 adults aged 68.65 ± 11.41 years participated in the study. IC was assessed with the WHO ICOPE screening tool, covering five domains: cognitive, locomotor, sensory, vision, and psychological capacity. We assessed the activities of daily living (ADL); instrumental activities of daily living (IADL); the Fried frailty phenotype; FRAIL scale; Strength, Assistance With Walking, Rising From chair, Climbing Stairs, and Falls (SARC-F) scale; Mini-mental State Examination (MMSE); Geriatric Depression Scale (GDS); social frailty; and quality of life. Results: There were 260 (69.1%) participants who showed declines in one or more IC dimensions. The percentages of decline in mobility, cognition, vitality, hearing, vision, and psychological capacity were 25.3, 46.8, 16.2, 15.4, 11.7, and 12.0%, respectively. IC decreased with increasing age. After adjusting for age, sex, and multimorbidity, participants with declines in IC were more likely to be older, frail, and disabled. They also had worse physical, mental, and overall health. There was a higher prevalence of declines in IC in participants with frailty. After adjusting for age, IC was positively correlated with walking speed, resilience score, and MMSE score and negatively correlated with frailty, SARC-F score, IADL score, GDS score, and physical and mental fatigue. The IC score was not associated with body composition variables such as fat-free mass, body fat percentage, or visceral fat area. Higher IC was associated with better quality of life. The area under the curve of the receiver operating characteristic (AUC-ROC) for the ICOPE screening tool vs. Fried phenotype, FRAIL, ADL disability, IADL disability, and SARC-F were 0.817, 0.843, 0.954, 0.912, and 0.909, respectively. Conclusion: Our research affirms that the ICOPE screening tool is useful to identify adults with poor physical and mental function in a Chinese sample. This tool may assist in identifying declines in IC in an integrative care model and help slow down function decline and onset of care dependence.

Dingxin recipe alleviates atherosclerosis injury in ApoE-knockout mice via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response.

OBJECTIVE: To further elucidate the mechanism underlying the anti-atherosclerotic effect of Dingxin recipe (DXR). METHODS: Fifty 6-week-old male ApoE-/- mice were randomly divided into the following groups: model, simvastatin (5 mg·kg－1·d－1), DXR low-dose (9.30 g·kg－1·d－1), DXR middle-dose (18.59 g·kg－1·d－1) and DXR high-dose (37.18 g·kg－1·d－1) (n = 10). Ten male C57BL/6J mice were used as the control group. All ApoE-/- mice were fed a high-fat diet (HFD) and the control mice received a common diet. After HFD for 12 weeks, the mice were treated with DXR or simvastatin for another 12 weeks. The expression of inflammatory cytokines and visfatin was determined in serum and atherosclerotic lesions by enzyme-linked immunosorbent assay. Visfatin expression was also assessed in aortic atherosclerotic plaques. Cultured vessel endothelial cells (VECs) were pretreated with DXR sera prior to visfatin. The effects of DXR were analyzed to elucidate its protective mechanism against visfatin-induced inflammation in VECs. RESULTS: DXR regulated blood lipids and reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and visfatin expression in ApoE-/- mice, particularly at the higher doses. The areas of atherosclerotic lesions in the DXR groups were significantly smaller than those in the model group. DXR alleviated visfatin-induced VEC injury via downregulation of TNF-α, IL-6, ICAM-1 and VCAM-1 through mitogen-activated protein kinase pathways. CONCLUSION: DXR alleviated atherosclerosis injury via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response in VECs.

Verticillium dahliae VdTHI20, Involved in Pyrimidine Biosynthesis, Is Required for DNA Repair Functions and Pathogenicity.

Verticillium dahliae (V. dahliae) infects roots and colonizes the vascular vessels of host plants, significantly reducing the economic yield of cotton and other crops. In this study, the protein VdTHI20, which is involved in the thiamine biosynthesis pathway, was characterized by knocking out the corresponding VdTHI20 gene in V. dahliae via Agrobacterium tumefaciens-mediated transformation (ATMT). The deletion of VdTHI20 resulted in several phenotypic defects in vegetative growth and conidiation and in impaired virulence in tobacco seedlings. We show that VdTHI20 increases the tolerance of V. dahliae to UV damage. The impaired vegetative growth of ΔVdTHI20 mutant strains was restored by complementation with a functional copy of the VdTHI20 gene or by supplementation with additional thiamine. Furthermore, the root infection and colonization of the ΔVdTHI20 mutant strains were suppressed, as indicated by green fluorescent protein (GFP)-labelling under microscope observation. When the RNAi constructs of VdTHI20 were used to transform Nicotiana benthamiana, the transgenic lines expressing dsVdTHI20 showed elevated resistance to V. dahliae. Together, these results suggest that VdTHI20 plays a significant role in the pathogenicity of V. dahliae. In addition, the pathogenesis-related gene VdTHI20 exhibits potential for controlling V. dahliae in important crops.

Negative regulation of PI3K/AKT/mTOR axis regulates fibroblast proliferation, apoptosis and autophagy play a vital role in triptolide-induced epidural fibrosis reduction.

Fibroblasts excessive proliferation was considered as a decisive reason for epidural fibrosis, which was known as a serious complication of lumbar laminectomy. As a traditional Chinese medicine, triptolide (TP) was used to be proved effective in preventing several fibrosis scar formation diseases. However, little is known about the effect of TP on preventing epidural fibrosis and its possible mechanism. Here, we performed in vitro and in vivo experiments to detect the possible mechanism of TP in preventing epidural fibrosis. In vitro, the effect of TP on impacting fibroblasts proliferation activities was detected by CCK-8, cell cycle assay and EdU incorporation assay. Also, the expressions of cell proliferation protein markers and the expressions of p-PI3K, p-AKT, p-mTOR were detect by Western blot. Besides, the effect of TP on inducing fibroblast apoptosis and autophagy was tested by Western blots, flow cytometry, TUNEL staining, Transmission electron microscope (TEM) analysis and LC3 immunofluorescent staining. The results suggested that TP could suppress the activation of PI3K/AKT/mTOR signaling pathway. Meanwhile, TP could inhibit fibroblast proliferation and induce fibroblast apoptosis as well as autophagy, which was known as two cellular self-destructions. Furthermore, we speculated the possible molecular pathway, through which that TP could inhibit fibroblast proliferation, induce fibroblast apoptosis and autophagy. We used PI3-kinase activator (740Y-P) to activate the PI3K/AKT/mTOR signaling. Activation of PI3K/AKT/mTOR signaling pathway increase the proliferation of fibroblasts and suppressed the autophagy and apoptosis induced by TP. In vivo, we built epidural fibrosis models in rats and locally applied TP of various concentrations. Hematoxylin-eosin (HE) and Masson's trichrome were used to detect the effect of TP on reducing epidural fibrosis. And the results showed that TP could significantly reduce the surgery-induced epidural fibrosis. In conclusion, the results above shown that TP could reduce epidural fibrosis formation, and the potential mechanism might through inhibiting fibroblast proliferation and stimulating apoptosis and autophagy via suppressing PI3K/AKT/mTOR signaling pathway. It might provide a novel thought for reducing surgery-induced epidural fibrosis.

Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat) with Diabetic Nephropathy.

Qufengtongluo (QFTL) decoction is an effective treatment for diabetic nephropathy (DN). However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-ß, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-ß mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-ß was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-ß.

Heavy metals in soils and sediments from Dongting Lake in China: occurrence, sources, and spatial distribution by multivariate statistical analysis.

Heavy metal contamination in soils/sediments and its impact on human health and ecological environment have aroused wide concerns. Our study investigated 30 samples of soils and sediments around Dongting Lake to analyze the concentration of As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn in the samples and to distinguish the natural and anthropogenic sources. Also, the relationship between heavy metals and the physicochemical properties of samples was studied by multivariate statistical analysis. Concentration of Cd at most sampling sites were more than five times that of national environmental quality standard for soil in China (GB 15618-1995), and Pb and Zn levels exceeded one to two times. Moreover, Cr in the soil was higher than the national environmental quality standards for one to two times while in sediment was lower than the national standard. The investigation revealed that the accumulations of As, Cd, Mn, and Pb in the soils, and sediments were affected apparently by anthropogenic activities; however, Cr, Fe, and Ni levels were impacted by parent materials. Human activities around Dongting Lake mainly consisted of industrial activities, mining and smelting, sewage discharges, fossil fuel combustion, and agricultural chemicals. The spatial distribution of heavy metal in soil followed the rule of geographical gradient, whereas in sediments, it was significantly affected by the river basins and human activities. The result of principal component analysis (PCA) demonstrated that heavy metals in soils were associated with pH and total phosphorus (TP), while in sediments, As, Cr, Fe, and Ni were closely associated with cation exchange capacity (CEC) and pH, where Pb, Zn, and Cd were associated with total nitrogen (TN), TP, total carbon (TC), moisture content (MC), soil organic matter (SOM), and ignition lost (IL). Our research provides comprehensive approaches to better understand the potential sources and the fate of contaminants in lakeshore soils and sediments.

[Material for evaluation of notoginseng total saponin preparation induced pseudoanaphylactoid reactions].

The experiment is designed to explore pathological festures and material basis of pseadoanaphylactoid reaction induced by notoginseng total saponin preparation. Mouse pseadoanaphylactoid reaction was used, 50 ICR mice were randomly assigned to control group, positive medicine group, notoginseng total saponin preparation low-dose group, notoginseng total saponin preparation middle-dose group, notoginseng total saponin preparation high-dose group on average. They are treated by intravenous injection of test substance solutions containing 0.4% Evans blue (EB). 30 min later, scores of ear blue staining and quantitation of ear EB exudation were recorded. Another two experiment were repeated in the same way excluding EB, just to. detect the related cytokines in serum using ELISA. We found that the scores of pseudoanaphylactoid reaction in notoginseng total saponin preparation injection middle-dose group and high-dose group was evidently higher than that in control group, suggesting that notoginseng total saponin preparation injection may be can lead to pseadoanaphylactoid reaction. HE staining showed that pseadoanaphylactoid reaction induced by notoginseng total saponin preparation injection is related to inflammation. Histamine, VEGF and TNF-α levels in notoginseng total saponin preparation middle-dose group and high-dose group significantly increased (P < 0.05, P < 0.01) than control group and showed a dose-dependent manner as well as consistent with the degree of ear blue dye. While IL-6 and IL-10 content did not increase significantly in notoginseng total saponin preparation low-dose group and middle-dose group, but they significantly higher than control group (P < 0.05, P < 0.01) when it increased to quadrupe clinical concentrations, eight times of the clinical dose. So pseadoanaphylactoid reaction caused by notoginseng total saponin preparation may be related to histamine, VEGF, TNF-α, and it is possible that IL-6 and IL-10 can play a role when pseadoanaphylactoid reaction achieve a certain high degree.

[Preliminary study on hepatotoxicity induced by dioscin and its possible mechanism].

Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 µmol · L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 µmol · L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A.

[Pharmacology research on PXR as a potential target in screening bioactive components of Chinese material medica].

Pregnane X receptor (PXR) is key transcription factors which mainly regulate the expression of CYP3A genes. At the molecular level, PXR has been revealed the protection mechanism of the body against xenochemicals and a major mode of the drug-drug interactions. Besides playing an important role in drug metabolism and interactions, PXR and its target genes also play an important role in maintaining normal physiological function and homeostasis. Therefore, it is necessary to study the regulation of PXR and its related pharmacological effects of TCM and natural products, and to provide new clues for the new pharmacological pathway.

Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced hepatocarcinogenesis: involvement of CCAAT/enhancer binding protein ß and cyclooxygenase-2.

Cyclooxygenase-2 (COX-2) and CCAAT/enhancer binding protein ß (C/EBPß) have been shown to be involved in inflammation and carcinogenesis, and our previous study revealed that they were co-overexpressed in human hepatocellular carcinoma (HCC) tissue and a positive correlation was found. Saikosaponin-d (SSD), a triterpene saponin extracted from Bupleurum falcatum L. (Umbelliferae), is known to exert inhibitory effects on COX-2 expression, together with inflammation and hepatic fibrosis. These findings prompted us to investigate the chemopreventive potential of SSD against hepatocarcinogenesis and its possible molecular mechanism in vivo. An experimental model with diethylinitrosamine (DEN)-treated Sprague Dawley rats was used in the present study. DEN (50 mg/kg body weight) and SSD (2 mg/kg body weight) were intraperitoneally injected weekly and daily, respectively. Administration of SSD alone had no side effects. The liver nodule formation, tumorous invasion to surrounding organs and increased cellular atypia induced by DEN were markedly reduced by SSD in the SSD + DEN group compared with the DEN group. On the other hand, immunohistochemical staining demonstrated that the expression of COX-2 and C/EBPß proteins was significantly increased in tumor cells and macrophages of liver tissue from DEN-treated rats, whereas the expression of the two proteins was markedly lowered in the SSD + DEN group. Overall, our results suggest that SSD prevents DEN-induced hepatocarcinogenesis in rats through inhibition of C/EBPß and COX-2, providing indispensable experimental evidence for the clinical application of SSD as a novel chemopreventive agent against HCC in the future.

Visuo-verbal interactions in working memory: evidence from event-related potentials.

Working memory is thought to involve separate modality-specific storage systems. Interactions between these storage systems were investigated using a novel cross-modal 2-back paradigm. 2-back, 1-back and target items were presented either visually as a verbalizable linedrawing or auditorily as a digitized spoken word. ERPs for auditory targets were primarily modulated by the presentation modality of the 2-back item, whereas ERPs for visual targets were largely modulated by presentation modality of the 1-back item. Results indicate that verbalizable pictures are only partially transformed into a phonological code for rehearsal in working memory. Furthermore, results support the idea of a more stable and persistent auditory short-term store as opposed to a more transiently activated visual store for verbalizable material.