Ginsenoside Re Attenuates Cisplatin-Induced Intestinal Toxicity via Suppressing GSK-3ß-Dependent Wnt/ß-Catenin Signaling Pathway In Vivo and In Vitro.

Previous reports have confirmed that crude saponins (ginsenosides) in Panax ginseng have a preventive effect on chemotherapy-induced intestinal injury. However, the protective effects and possible mechanisms of ginsenoside Re (G-Re, a maker saponin in ginseng) against chemotherapy-induced intestinal damage have not been thoroughly studied. In this work, a series of experiments in vivo and in vitro on the intestinal toxicity caused by cisplatin have been designed to verify the improvement effect of G-Re, focusing on the levels of Wnt3a and [Formula: see text]-catenin. Mice were intragastric with G-Re for 10 days, and intestinal injury was induced by intraperitoneal administration of cisplatin at a dose of 20 mg/kg. Histopathology, gastrointestinal digestive enzyme activities, inflammatory cytokines, and oxidative status were evaluated to investigate the protective effect. Furthermore, in IEC-6 cells, G-Re statistically reverses cisplatin-induced oxidative damage and cytotoxicity. The TUNEL and Hoechst 33258 staining demonstrated that G-Re possesses protective effects in cisplatin-induced apoptosis. Additionally, pretreatment with G-Re significantly alleviated the apoptosis via inhibition of over-expressions of B-associated X (Bax), as well as the caspase family members, such as caspase 3 and 9, respectively, in vivo and in vitro. Notably, western blotting results showed that G-Re treatment decreased Wnt3a, Glycogen synthase kinase [Formula: see text] (GSK-[Formula: see text]), and [Formula: see text]-catenin expression, suggesting that nuclear accumulation of [Formula: see text]-catenin was attenuated, thereby inhibiting the activation of GSK-[Formula: see text]-dependent Wnt/[Formula: see text]-catenin signaling, which was consistent with our expected results. Therefore, the above evidence suggested that G-Re may be a candidate drug for the treatment of intestinal injury.

Hydrolytically Stable Zr-Based Metal-Organic Framework as a Highly Sensitive and Selective Luminescent Sensor of Radionuclides.

Effective detections of radionuclides including uranium and its predominant fission products, for example, iodine, are highly desired owing to their radiotoxicity and potential threat to human health. However, traditional analytical techniques of radionuclides are instrument-demanding, and chemosensors targeted for sensitization of radionuclides remain limited. In this regard, we report a sensitive and selective sensor of UO22+ and I- based on the unique quenching behavior of a luminescent Zr-based metal-organic framework, Zr6O4(OH)4(OH)6(H2O)6(TCPE)1.5·(H2O)24(C3H7NO)9 (Zr-TCPE). Immobilization of the luminescent tetrakis(4-carboxyphenyl)ethylene (TCPE4-) linkers by Zr6 nodes enhances the photoluminescence quantum yield of Zr-TCPE, which facilitates the effective sensing of radionuclides in a "turn-off" manner. Moreover, Zr-TCPE can sensitively and selectively recognize UO22+ and I- ions with the lowest limits of detection of 0.67 and 0.87 µg/kg, respectively, of which the former one is much lower than the permissible value (30 µg/L) defined by the U.S. EPA. In addition, Zr-TCPE features excellent hydrolytic stability and can withstand pH conditions ranging from 3 to 11. To facilitate real-world applications, we have further fabricated polyvinylidene fluoride-integrating Zr-TCPE as luminescence-based sensor membranes for on-site sensing of UO22+ and I-.

Protective Effect of 20(R)-Ginsenoside Rg3 Against Cisplatin-Induced Renal Toxicity via PI3K/AKT and NF-[Formula: see text]B Signaling Pathways Based on the Premise of Ensuring Anticancer Effect.

Although the protective effect of ginsenoside on cisplatin-induced renal injury has been extensively studied, whether ginsenoside interferes with the antitumor effect of cisplatin has not been confirmed. In this paper, we verified the main molecular mechanism of 20(R)-ginsenoside Rg3 (R-Rg3) antagonizing cisplatin-induced acute kidney injury (AKI) through the combination of in vivo and in vitro models. It is worth mentioning that the two cell models of HK-2 and HepG2 were used simultaneously for the first time to explore the effect of the activation site of tumor-associated protein p53 on apoptosis and tumor suppression. The results showed that a single injection of cisplatin (20 mg/kg) led to weight loss, the kidney index of the mice increased, and creatinine (CRE) and blood urea nitrogen (BUN) levels in mice sharply increased. Continuous administration of R-Rg3 at doses of 10 and 20 mg/kg for 10 days could significantly alleviate this symptom. Similarly, R-Rg3 treatment reduced oxidative stress damage caused by cisplatin. Moreover, R-Rg3 could observably reduce the apoptosis and inflammatory infiltration of renal tubular cells induced by cisplatin. We used western blotting analysis to demonstrate that R-Rg3 restored cisplatin-induced AKI might be related to PI3K/AKT and NF-[Formula: see text]B mediated apoptosis and inflammation pathways. In the meantime, we also verified that R-Rg3 could activate different sites of p53 to control renal cell apoptosis induced by cisplatin without affecting its antitumor effect.

Efficiently immobilizing uranium (VI) by oxidized carbon foam.

Oxidized carbon foam (oxidized CF) was prepared by using a facile chemical oxidation treatment at relatively low temperature of 450 °C and applied to capture uranyl cation [U(VI)] from aqueous solutions. The effects of pH, contact time, initial U(VI) concentration, and temperature on the U(VI) absorption performance of oxidized CF were investigated by batch experiments. The oxidized CF was illustrated to exhibit fast sorption kinetics (92% removal within 15 min and 98% removal in 2 h) and high sorption capacity (305.77 mg g-1 at pH 5) toward U(VI). Integrated analyses combining energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy were applied on the U(VI)-loaded oxidized CF, showing the introduction of carboxyl groups as U(VI) sorption sites on the surface of CF after oxidation treatment. Furthermore, extended X-ray absorption fine structure spectroscopy was employed to identify the binding modes of U(VI) indicating that each UO22+ cation is coordinated with one or two carboxyl groups on the equatorial plane. Notably, the low content of U(VI) in wastewater can be efficiently immobilized by the oxidized CF, and the immobilized U(VI) can be further concentrated and converted into Na2U2O7 or U3O8 by a simple sintering step. These findings presented in this work suggest the potential of using oxidized CF for further treatment of low concentration wastewater containing U(VI).

Rare Ginsenoside 20(R)-Rg3 Inhibits D-Galactose-Induced Liver and Kidney Injury by Regulating Oxidative Stress-Induced Apoptosis.

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.

Red ginseng protects against cisplatin-induced intestinal toxicity by inhibiting apoptosis and autophagy via the PI3K/AKT and MAPK signaling pathways.

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg-1) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg-1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.

Meta-analysis of oxaliplatin-based versus fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer.

A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched for relevant randomized controlled trials (RCTs) until January 31 2017. Review Manager (version 5.3) was used to analyze the data. Dichotomous data were calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8 RCTs with 6103 stage II or III rectal cancer patients were analyzed, including 2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with fluorouracil alone regimen. Compared with fluorouracil-based regimen group, oxaliplatin-based regimen group attained higher pathologic complete response (OR = 1.29, 95% CI: 1.12-1.49, P = 0.0005) and 3-year disease-free survival (OR = 1.15, 95% CI: 0.93-1.42, P = 0.21), but suffered greater toxicity (OR = 2.07, 95% CI: 1.52-2.83, P < 0.00001). Also, there were no significant differences between two regimens in sphincter-sparing surgery rates (OR = 0.94, 95% CI: 0.83-1.06, P = 0.33), 5-year disease-free survival (OR = 1.15, 95% CI: 0.93-1.42, P = 0.21) and overall survival (3-year, OR = 1.14, 95% CI: 0.98-1.34, P = 0.09; 5-year, OR = 1.06, 95% CI: 0.78-1.44, P = 0.70). In conclusion, the benefits of adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer remains controversial, and cannot be considered a standard approach.

Direct Methylation of Amines with Carbon Dioxide and Molecular Hydrogen using Supported Gold Catalysts.

The N-methylation of amines with CO2 and H2 is an important step in the synthesis of bioactive compounds and chemical intermediates. The first heterogeneous Au catalyst is reported for this methylation reaction with good to excellent yields. The average turnover frequency (TOF) based on surface Au atoms is 45 h(-1) , which is the highest TOF value ever reported for the methylation of aniline with CO2 and H2 . Furthermore, the catalyst is tolerant toward a variety of amines, which includes aromatic, aliphatic, secondary, and primary amines. Preliminary mechanistic studies suggest that the N-alkyl formamide might be an intermediate in the N-methylation of amine process. Moreover, through a one-pot process, it is possible to convert primary amines, aldehydes, and CO2 into unsymmetrical tertiary amines with H2 as a reductant in the presence of the Au catalyst.

[Differences of Cynomorium songaricum seed quality and mutual parasitism in different host plants].

In natural conditions, fully ripe Cynomorium songaricum seeds parasitize in Nitraria tangutorum or N. sphaerocarpa or N. sibirica or Zygophyllum xanthoxylom and Peganum harmala, were used in this study to research the morphological characteristics, embryo rate, seed viability, 1 000-grain weight, purity, water content and the seeds of different host parasitic relationship with each other. The results showed that the morphology, color and surface characteristics of the C. songaricum seeds are very similar in different hosts. According to the seed morphology can not be judged on its host. For the host to N. tangutorum or Peganum harmala or N. sibirica, we should choose the round hole screen less than 0.923 1 mm and larger than 1.066 2 mm to cleaning seeds. For the C. songaricum seeds parasitic in N. sphaerocarpa, the choice of slightly less than 0.926 1 mm and larger than 0.985 3 mm round hole screen to cleaning. For the parasitic seeds in Z. xanthoxylom, less than 0.751 3 mm and slightly larger than 1.035 3 mm round hole screen could be used. Highy significant correlation was found among the morphological indexes in C. songaricum seeds (P < 0.01). Morphological indexes and 1 000-grain weight were significantly correlated (0.01 < P < 0.05), but with the seed viability and the embryo rate were not found significant correlation. Grain weight is not related with the seed viability and the Fully mature C. songaricum seed viability is high and water content is low. The difference of the habitats and the host plants should be considered in the seed quality assessment and classification. The C. songaricum seeds on host plants are not selective, and the C. songaricum seeds from the host plants could be parasitized in other host plants.

In vitro and in vivo efficacies of teicoplanin-loaded calcium sulfate for treatment of chronic methicillin-resistant Staphylococcus aureus osteomyelitis.

The in vitro and in vivo therapeutic efficacies of teicoplanin-loaded calcium sulfate (TCS; 10% [wt] teicoplanin) were investigated in a rabbit model of chronic methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. The in vitro elution characteristics of teicoplanin from TCS pellets were realized by carrying out an evaluation of the release kinetics, recovery rate, and antibacterial activity of the released teicoplanin. Chronic osteomyelitis was induced by inoculating 10(7) CFU of a MRSA strain into the tibial cavity of rabbits. After 3 weeks, the animals were treated by debridement followed by implantation of TCS pellets in group 1, calcium sulfate (CS) pellets alone in group 2, and intravenous (i.v.) teicoplanin (6 mg/kg of body weight every 12 h for three doses and then every 24 h up to 4 weeks) in group 3. Animals in group 4 were left untreated. After 6 weeks, the efficacy of the osteomyelitis treatment was evaluated by hematological, radiological, microbiological, and histological examinations. In vitro elution studies showed sustained release of teicoplanin at a therapeutic level over a time period of 3 weeks. The released teicoplanin maintained its antibacterial activity. In vivo, the best therapeutic effect was observed in animals treated with TCS pellets, resulting in significantly lower radiological and histological scores, lower positive rates of MRSA culture and bacterial load, and excellent bone regeneration compared with those treated by CS alone or i.v. teicoplanin, without any local or systemic adverse effects. TCS pellets are an effective alternative to i.v. teicoplanin for the treatment of chronic MRSA osteomyelitis, particularly because teicoplanin is delivered locally while the TCS pellets simultaneously promote bone defect repair.