Selenium Increased Arsenic Accumulation by Upregulating the Expression of Genes Responsible for Arsenic Reduction, Translocation, and Sequestration in Arsenic Hyperaccumulator Pteris vittata.

Selenate enhances arsenic (As) accumulation in As-hyperaccumulator Pteris vittata, but the associated molecular mechanisms are unclear. Here, we investigated the mechanisms of selenate-induced arsenic accumulation by exposing P. vittata to 50 µM arsenate (AsV50) and 1.25 (Se1.25) or 5 µM (Se5) selenate in hydroponics. After 2 weeks, plant biomass, plant As and Se contents, As speciation in plant and growth media, and important genes related to As detoxification in P. vittata were determined. These genes included P transporters PvPht1;3 and PvPht1;4 (AsV uptake), arsenate reductases PvHAC1 and PvHAC2 (AsV reduction), and arsenite (AsIII) antiporters PvACR3 and PvACR3;2 (AsIII translocation) in the roots, and AsIII antiporters PvACR3;1 and PvACR3;3 (AsIII sequestration) in the fronds. The results show that Se1.25 was more effective than Se5 in increasing As accumulation in both P. vittata roots and fronds, which increased by 27 and 153% to 353 and 506 mg kg-1. The As speciation analyses show that selenate increased the AsIII levels in P. vittata, with 124-282% more AsIII being translocated into the fronds. The qPCR analyses indicate that Se1.25 upregulated the gene expression of PvHAC1 by 1.2-fold, and PvACR3 and PvACR3;2 by 1.0- to 2.5-fold in the roots, and PvACR3;1 and PvACR3;3 by 0.6- to 1.1-fold in the fronds under AsV50 treatment. Though arsenate enhanced gene expression of P transporters PvPht1;3 and PvPht1;4, selenate had little effect. Our results indicate that selenate effectively increased As accumulation in P. vittata, mostly by increasing reduction of AsV to AsIII in the roots, AsIII translocation from the roots to fronds, and AsIII sequestration into the vacuoles in the fronds. The results suggest that selenate may be used to enhance phytoremediation of As-contaminated soils using P. vittata.

Mechanism of Action of Shenerjiangzhi Formulation on Hyperlipidemia Induced by Consumption of a High-Fat Diet in Rats Using Network Pharmacology and Analyses of the Gut Microbiota.

Shenerjiangzhi formulation (SEJZ) is a new traditional Chinese medicine formulation (patent number: CN110680850A). SEJZ contains Eleutherococcus senticosus (Rupr. and Maxim.), Maxim (Araliaceae; E. senticosus radix and rhizome), Lonicera japonica Thunb (Caprifoliaceae; Lonicera japonica branch, stem), Crataegus pinnatifida Bunge (Rosaceae; Crataegus pinnatifida fruit), and Auricularia auricula. SEJZ has been designed to treat hyperlipidemia. Despite the therapeutic benefits of SEJZ, its underlying mechanism of action is not known. We explored the efficacy of SEJZ against hyperlipidemia by integrating network pharmacology and 16S rRNA gene sequencing and elucidated its mechanism of action. First, SEJZ targets were found through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and from the literature. Hyperlipidemia-related therapeutic targets were obtained from GeneCards, Online Mendelian Inheritance in Man, and DrugBank databases. Then, Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape were applied for the analyses and construction of a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes database was employed to identify signaling pathways that were enriched. Second, the therapeutic effects of SEJZ against hyperlipidemia induced by consumption of a high-fat diet in rats were evaluated by measuring body weight changes and biochemical tests. SEJZ treatment was found to alleviate obesity and hyperlipidemia in rats. Finally, 16S rRNA gene sequencing showed that SEJZ could significantly increase the abundance of short-chain fatty acid-producing bacteria, restore the intestinal barrier, and maintain intestinal-flora homeostasis. Using PICRUSt2, six metabolic pathways were found to be consistent with the results of network pharmacology: "African trypanosomiasis", "amoebiasis", "arginine and proline metabolism", "calcium signaling pathway", "NOD-like receptor signaling pathway", and "tryptophan metabolism". These pathways might represent how SEJZ works against hyperlipidemia. Moreover, the "African trypanosomiasis pathway" had the highest association with core genes. These results aid understanding of how SEJZ works against dyslipidemia and provide a reference for further studies.

Rabeprazole plus amoxicillin dual therapy is equally effective to bismuth-containing quadruple therapy for Helicobacter pylori eradication in central China: A single-center, prospective, open-label, randomized-controlled trial.

BACKGROUND: Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate. METHODS: This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test. RESULTS: In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group. CONCLUSIONS: Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization.

Tai Chi and other mind-body interventions for cancer-related fatigue: an updated systematic review and network meta-analyses protocol.

INTRODUCTION: Fatigue is one of the most common symptoms in patients with cancer and is responsible for a reduced quality of life. There is a strong evidence base for mind-body interventions (MBIs) to manage cancer-related fatigue (CRF). However, the efficacy of Tai Chi and other MBIs in the treatment of CRF remains controversial. METHODS AND ANALYSIS: We will perform a systematic review and network meta-analyses (NMAs) that aim to assess the effects of Tai Chi and other MBIs in patients with CRF. The following databases will be searched from their inception to 1 August 2021: PubMed, EMBASE, Scopus, OVID, Web of Science, Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese Biomedical Database and Wan Fang Digital Journals. We will include randomised controlled trials that compare MBIs with no treatment, placebo and usual care in the treatment of CRF. The primary outcome will be changes in the fatigue state as evaluated by validated scales. We will perform a Bayesian NMA to analyse all the evidence for each outcome. The surface under the cumulative ranking curve and the mean ranks will be used to rank the various treatments. We will assess the quality of evidence contributing to network estimates of outcomes using the Grading of Recommendations Assessment, Development and Evaluation system framework. ETHICS AND DISSEMINATION: This NMAs will be disseminated through publication in a peer-reviewed journal. Since no individual patient data will be involved in the review, ethics approval and concerns about privacy are not needed. PROSPERO REGISTRATION NUMBER: CRD42021244999.

Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent.

A three-component drug-delivery system has been developed consisting of multi-walled carbon nanotubes (MWCNTs) coated with a non-classical platinum chemotherapeutic agent ([PtCl(NH3)2(L)]Cl (P3A1; L=N-(2-(acridin-9-ylamino)ethyl)-N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (DSPE-mPEG). The optimized P3A1-MWCNTs are colloidally stable in physiological solution and deliver more P3A1 into breast cancer cells than treatment with the free drug. Furthermore, P3A1-MWCNTs are cytotoxic to several cell models of breast cancer and induce S-phase cell cycle arrest and non-apoptotic cell death in breast cancer cells. By contrast, free P3A1 induces apoptosis and allows progression to G2/M phase. Photothermal activation of P3A1-MWCNTs to generate mild hyperthermia potentiates their cytotoxicity. These findings suggest that delivery of P3A1 to cancer cells using MWCNTs as a drug carrier may be beneficial for combination cancer chemotherapy and photothermal therapy.

YiXin-Shu, a ShengMai-San-based traditional Chinese medicine formula, attenuates myocardial ischemia/reperfusion injury by suppressing mitochondrial mediated apoptosis and upregulating liver-X-receptor α.

Positive evidence from clinical trials has fueled growing acceptance of traditional Chinese medicine (TCM) for the treatment of cardiac diseases; however, little is known about the underlying mechanisms. Here, we investigated the nature and underlying mechanisms of the effects of YiXin-Shu (YXS), an antioxidant-enriched TCM formula, on myocardial ischemia/reperfusion (MI/R) injury. YXS pretreatment significantly reduced infarct size and improved viable myocardium metabolism and cardiac function in hypercholesterolemic mice. Mechanistically, YXS attenuated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway (as reflected by inhibition of mitochondrial swelling, cytochrome c release and caspase-9 activity, and normalization of Bcl-2 and Bax levels) without altering the death receptor and endoplasmic reticulum-stress death pathways. Moreover, YXS reduced oxidative/nitrative stress (as reflected by decreased superoxide and nitrotyrosine content and normalized pro- and anti-oxidant enzyme levels). Interestingly, YXS upregulated endogenous nuclear receptors including LXRα, PPARα, PPARß and ERα, and in-vivo knockdown of cardiac-specific LXRα significantly blunted the cardio-protective effects of YXS. Collectively, these data show that YXS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and oxidative stress and by upregulating LXRα, thereby providing a rationale for future clinical trials and clinical applications.

Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk.

In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and ß-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2-TNF-α- CD8 T cells and IFN-γ+IL-2-TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals.

[Effects of phosphorus fertilizer on the root system and its relationship with the aboveground part of flue-cured tobacco].

Using 'Yuyan 10' as the material, the effects of different phosphorus fertilizer application on root characteristics of tobacco, such as root dry mass and the difference of dry matter distribution and mineral nutrient accumulation between its above and underground parts were investigated. The results showed that the growth of flue-cured tobacco root system and the distribution of dry matter to the aboveground part were significantly promoted by phosphorus fertilizer application. The application of 30 kg P2O5 · hm(-2) led to the maximums of root dry mass, root volume, root activity and the minimum of root to shoot ratio. The maximum nutrient accumulation rates of root and leaf appeared 57-66 days after transplanting and 44-55 days after transplanting, respectively. Phosphorus could not only promote the mineral nutrition absorption of tobacco and the earlier appearance of maximum nutrient accumulation, but significantly promote the nutrient accumulation of the aboveground part. But, the positive effects described above would be weakened when the amount of phosphorus fertilizer was more than 30 kg P2O5 · hm(-2). Therefore, it's necessary to control the amount of phosphorus application to improve the quality of tobacco leaves.

The effect of tetramethylpyrazine on hydrogen peroxide-induced oxidative damage in human umbilical vein endothelial cells.

Tetramethylpyrazine has been widely used in traditional Chinese medicine to treat cardiovascular diseases such as atherosclerosis and hypertension. The underlying mechanism of cardioprotective effects, however, remains to be elucidated. Here, using human umbilical vein endothelial cells (HUVECs), we have assessed the protective effect of tetramethylpyrazine on H(2)O(2)-induced oxidative damage. After pre-incubation with tetramethylpyrazine (50, 100 and 150 microg/ml) for 24 hr., viability loss in H(2)O(2)-induced HUVECs (76.5% of the control level, p < 0.05, at 400 microM of H(2)O(2) for 12 hr.) was restored in a concentration-dependent manner, and the maximal recovery (88.7% of the control level, p < 0.05) was achieved with tetramethylpyrazine at 150 microg/ml. The production of reactive oxygen species was suppressed by measuring fluorescent intensity of 2',7'-dichorofluorescein (83.1% of the H(2)O(2)-treated group, p < 0.05, at 150 microg/ml of tetramethylpyrazine). Tetramethylpyrazine also increased activities of superoxide dismutase and glutathione peroxidase (144.1% and 118.3% of the H(2)O(2)-treated group, respectively, p < 0.05, at 150 microg/ml of tetramethylpyrazine). In addition, tetramethylpyrazine reduced levels of malonaldehyde, intracellular nitric oxide and nitric oxide synthase (83.8%, 91.2% and 78.7% of the H(2)O(2)-treated group, respectively, p < 0.05, at 150 microg/ml of tetramethylpyrazine). Furthermore, pre-incubation of tetramethylpyrazine with HUVECs for 24 hr. resulted in reduction of apoptosis and removal of cell cycle arrest in the S phase (56.6% and 59.7% of the H(2)O(2)-treated group, respectively, p < 0.01, at 150 microg/ml of tetramethylpyrazine). Altogether, these results suggest that tetramethylpyrazine has a protective effect on H(2)O(2)-induced oxidative damage in HUVECs due to its antioxidant and antiapoptotic properties.

[Analysis of RAPD on medicinal plants of Codonopsis pilosula].

OBJECTIVE: To study genetic diversity and genetic relationship among 9 cultivated and 4 nature populations of Codonopsis pilosula and C. pilosula var. modesta form Gansu Province at DNA level. METHODS: DNA of 217 individuals was amplified by 14 decamer primers from 200 radom primers. The polymorphic bands of RAPD were counted. And the results were analyzed by clustering analysis NTSYS-PC software. RESULTS: A total of 125 loci were detected by 14 arbitrary primers, among which 109 and 106 loci were polymorphic in C. pilosula and C. pilosula var. modesta respectively, and the percentage of polymorphic bands (PPB) were 87.20% and 84. 80%. The cluster analysis showed that 13 populations were divided into 2 groups. The one included 8 cultivated populations of C. pilosula, the other group consisted of a cultivated population and 4 nature populations of C. pilosula var. modesta. CONCLUSION: The RAPD results indicated that there was abundant genetic diversity in cultivated populations of C. pilosula and C. pilosula var. modesta. The genetic differentiation among 8 cultivated populations of C. pilosula was very small and related to their geographical distance. Only the cultivation in Wen County originated from C. pilosula var. modesta, while the other populations cultivated in Gansu Province belongs to C. pilosula.