Response of Vicia faba to short-term uranium exposure: chelating and antioxidant system changes in roots.

Uranium (U) phytotoxicity is an inherently difficult problem in the phytoremediation of U-contaminated environments. Plant chelating and antioxidant systems play an authoritative role in resistance to abiotic stress. To reveal the toxicity of U, the changes of chelating system, osmoregulatory substances and antioxidant systems in Vicia faba roots were studied after short-term (24 h) U exposure. The results indicated that the development of lateral roots and root activity of V. faba were significantly inhibited with U accumulation. Compared with the control, plant chelating systems showed significant positive effects after U exposure (15 - 25 µM). Osmoregulatory substances (proline and soluble protein) increasingly accumulated in roots with increasing U concentration, and O2- and H2O2 rapidly accumulated after U exposure (15 - 25 µM). Thus, the contents of malondialdehyde (MDA), a marker of lipid peroxidation, were also significantly increased. Antioxidant systems were activated after U exposure but were inhibited at higher U concentrations (15 - 25 µM). In summary, although the chelating, osmotic regulation and antioxidant systems in V. faba were activated after short-term U exposure, the antioxidases (CAT, SOD and POD) were inhibited at higher U concentrations (15 - 25 µM). Therefore, the root cells were severely damaged by peroxidation, which eventually resulted in inhibited activity and arrested root development.

Lingguizhugan Decoction Targets Intestinal Microbiota and Metabolites to Reduce Insulin Resistance in High-Fat Diet Rats.

Background: The increasing incidence of obesity and its complications has become a global public health problem. Lingguizhugan decoction (LGZGD) is a representative compound of traditional Chinese medicine (TCM) for metabolic diseases, such as nonalcoholic fatty liver disease, but its role in insulin resistance (IR) treatment is still less known. This study aims to evaluate the therapeutic properties of LGZGD on obesity-induced IR and explore the potential mechanism of LGZGD on gut microbiota and its metabolites in the treatment of IR. Methods: In this study, we induced an IR model in the form of high-fat diet (HFD) rats gavaged with LGZGD (1.64 g/kg BW) for three weeks. The IR status was measured by biochemical assays and oral glucose tolerance tests. The degrees of damage to liver function and the intestinal barrier were observed by hematoxylin and eosin (H&E) staining and immunohistochemistry. Alterations in intestinal microbiota and metabolites were assessed by 16S rRNA and an untargeted metabolomics platform. Results: Our results showed that after LGZGD treatment, the body weight, plasma insulin concentration and blood lipids were significantly decreased, and glucose tolerance and hepatic steatosis were ameliorated. In addition, small intestinal villi were restored, and the expression of Occludin was upregulated. The relative abundance of Akkermansia, Faecalibacterium and Phascolarctobacterium in the HFD-LGZG group was upregulated. Obesity-related metabolic pathways, such as bile secretion, biosynthesis of amino acids, phenylalanine metabolism, serotonergic synapse, protein digestion and absorption, taurine and hypotaurine metabolism, and primary bile acid biosynthesis, were changed. After LGZGD intervention, metabolites developed toward the healthy control group. In addition, the expression of bile acid metabolism related genes was also regulated in IR rats. Conclusion: We showed that LGZGD relieved IR, possibly by regulating the composition of the fecal microbiota and its metabolites. The above studies provide a basis for further study of LGZGD in the treatment of IR and its clinical application.

Electroacupuncture facilitates M2 macrophage polarization and its potential role in the regulation of inflammatory response.

The underlying mechanism of electroacupuncture (EA) in relieving obesity, anti-inflammation and the interaction with metabolic pathways in obese mice has not been elaborated. The aim of this study was to investigate the regulation of EA on macrophage polarization in obesity tissue of diet-induced obesity mice. Mice were divided in 6 groups: normal control group, model group, EA-7 group, EA-14 group, EA-21 group and EA-28 group. Low-frequency EA was applied at "Tianshu (ST 25)", "Guanyuan (CV 4)", "Zusanli (ST 36)" and "Sanyinjiao (SP 6)" for 10 min. Adipose tissue was assessed with hematoxylin and eosin staining. Adipocytokines and pro-inflammatory factors expression was measured by ELISA. The protein and mRNA levels of macrophage markers were examined by immumohistochemical staining and RT-PCR, respectively. EA treatment was associated with a decrease of adipose tissue and large adipocytes, and an increase of small adipocytes. After EA treatment, the levels of Leptin, Chemerin, TNF-α, F4/80, iNOS, and CD11c decreased obviously in adipose tissue, while IL-4, IL-10 and CD206 levels increased significantly. Besides, TNF-α in spleen tissue was also downregulated, but IL-4 and IL-10 were upregulated. EA prevents weight gain through modulation inflammatory response and macrophage polarization in obese adipose tissues.

Hypocalcemia with Immune Checkpoint Inhibitors: The Disparity among Various Reports.

Immune-related adverse events affecting parathyroid function are rarely reported with immune checkpoint inhibitors (ICPIs). Activating calcium-sensing receptor antibodies causing autoimmune hypoparathyroidism with nivolumab was recently reported. KEYNOTE-189 and CHECKMATE-067 trials reported a 21-29% hypocalcemia event rate, but the etiology of hypocalcemia was not reported. A chart review was performed to study patients receiving ICPI from 2015 to 2018 at multiple sites affiliated with Saint Vincent Hospital. The study population was divided into two groups based on the presence or absence of calcium altering conditions or medications. True hypocalcemia incidence was calculated after correcting calcium for albumin from the initiation of ICPI to their last follow-up. Group 1 (n = 83) includes patients with no calcium altering conditions or medications. Group 2 (n = 98) includes patients on calcium supplements (n = 17), vitamin D (n = 44), bisphosphonates (n = 24), >stage IIIB chronic kidney disease (CKD) (n = 5), and bone metastasis (n = 38). Hypocalcemia events in Group 1 vs. Group 2 were 8.4% and 19.3%, respectively. Our entire study demonstrated 26.8% vs. 1.1% of Grade I vs. II hypocalcemia events. However, after correcting the calcium for albumin, hypocalcemia incidence was 0.56% (n = 1). No further workup was done to investigate the etiology as that patient passed away. Our data suggest that the true hypocalcemia incidence after using albumin-corrected calcium values is very low in patients receiving IPCI, even in the presence of calcium altering factors. The percentage of patients with hypocalcemia is much higher and similar to the KEYNOTE-189 and CHECKMATE-067 trials when serum calcium values without albumin correction are used. Thus, the higher reported incidence of hypocalcemia in these trials is likely due to the reporting of serum calcium without albumin correction.

[Chemical constituents from seeds of Vigna umbellata].

Phytochemical investigation was carried out on the seeds of Vigna umbellata. The 70% ethanol extract of the seeds of V. umbellata was subjected to silica gel, Sephadex LH-20, ODS column chromatographies and preparative HPLC. The structures of the isolated compounds were elucidated on the basis of NMR and ESI-MS spectroscopic data Eight compounds were obtained and identified as carboxyatractyligenin (1), 2beta-O-beta-D-glucopyranosyl-15alpha-hydroxy-kaur-16-ene-18,19-dicarboxylic acid (2), 2beta-O-(beta-D-glucopyranosyl) atractyligenin (3), 3R-O-[beta-L-arabinopyranosyl-(1-6) -beta-D-glucopyranosyl] oct-1-ene-3-ol (4), (6S, 7E, 9R) -roseoside (5), liriodendrin (6), resveratrol (7) and maltol (8). Compounds 1-7 were isolated from Vigna genus for the first time, and compound 8 was isolated from V. umbellata for the first time.

Inhibitory effects of water caltrop pericarps on the growth of human gastric cancer cells in vitro.

Water caltrop is a popular traditional vegetable in China, and its pericarps are always wasted. In the present work reported here, pericarps from three different Chinese water caltrop cultivars were collected and extracted using 70% methanol and hot water. All the extracts contained significant amounts of polyphenols (183.7-201.7 mg GAE/g), flavonoids (34.3-54.6 mg RE/g) and saponins (23.2- 36.3 mg GRE/g). These extracts exhibited strong antioxidant capacity as assessed by DPPH, ABTS and FRAP methods. High correlations were found in DPPH, ABTS and polyphenols, FRAP and saponins. All the three extracts inhibited proliferation of SGC7901 human gastric cancer cells and HepG2 human hepatocarcinoma cells in a dose dependent manner without detectable cytotoxicity on HUVEC normal cells. Flow cytometry showed that apoptosis of SGC7901 and HepG2 cells was induced by water caltrop extracts while HUVEC cells were relatively resistant to apoptosis. Hot water extracts showed similar bioactivities as methanol extracts, which indicated that hot water could be used to extract bioactive compounds instead of organic solvents. These results suggest that water caltrop pericarps could be explored for their potential as anti-cancer drugs in future studies.

A rapid and sensitive HPLC-MS/MS analysis and preliminary pharmacokinetic characterization of sibiricaxanthone F in rats.

A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantifying sibiricaxanthone F (SF) in rat plasma following oral and intravenous dosings. After addition of the internal standard (IS) kaempferol and the antioxidant, 20% ascorbic acid, plasma samples were precipitated with acetonitrile and separated on an Aglient Zorbax XDB-C(18) column (50 mm × 4.6mm I.D., 2.1 µm) with gradient acetonitrile and water (both containing 0.01% formic acid) as the mobile phase. The detection was performed on a Sciex API 4000 LC-MS/MS with electrospray ionization (ESI) inlet in the negative multiple reaction monitoring (MRM) mode. Good linearity was achieved over the concentration range of 0.5-500.0ng/mL (r>0.996). Intra- and inter-day precisions were less than 7.60%, and accuracy ranged from 97.18% to 99.84%. The lower limit of quantification for SF was 0.5 ng/mL, and analytes were stable under various conditions (during freeze-thaw, at room temperature and under deep-freeze conditions). This validated method was successfully applied to the preliminary pharmacokinetic study of SF in rats for the first time, and the absolute bioavailability of SF was found to be only 0.22 ± 0.15%.

[Expression characteristics of prolactin gene in Eastern Zhejiang white geese].

This study was conducted to clone the prolactin gene (PRL) in Eastern Zhejiang White Geese and to investigate the PRL gene expression characteristics during egg-laying, out-of-lay and incubating periods by real time PCR. Comparisons were made respectively of concentration of prolactin mRNA in the hypothalamus, pituitary gland and ovary of the adult female geese at different reproductive periods. The result indicated that there were significant differences (P<0.05) in PRL mRNA expression between different reproductive periods of the geese. The lowest level of PRL expression was found in out-of-lay geese, higher in the egg-laying geese, and the highest in incubating geese. Furthermore, the analysis of PRL expression in different tissues indicated that the highest levels of PRL was expressed in the pituitary gland, followed in hypothalamus, and the least in ovary of the geese. There were significant difference (P<0.01) expression of PRL between the pituitary gland/hypothalamus and ovary of the geese, whereas no any difference was observed between the pituitary gland and hypothalamus (P>0.05). In summary, the PRL mRNA expression had variance in different reproductive periods of the geese.