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Abstract Background Panax notoginseng is a medicinally important Chinese herb with a long history of cultivation and clinical application. The planting area is mainly distributed in Wenshan Prefecture, where the quality and safety of P. notoginseng have been threatened by high concentration of arsenic (As) from the soil. The roles of phosphate (Pi) transporters involved in Pi acquisition and arsenate (AsV) tolerance were still unclear in this species. Results In this study, two open reading frames (ORFs) of PnPht1;1 and PnPht1;2 separated from P. notoginseng were cloned based on RNA-seq, which encoded 527 and 541 amino acids, respectively. The results of relative expression levels showed that both genes responded to the Pi deficiency or As exposure, and were highly upregulated. Heterologous expression in Saccharomyces cerevisiae MB192 revealed that PnPht1;1 and PnPht1;2 performed optimally in complementing the yeast Pi-transport defect, particularly in PnPht1;2. Cells expressing PnPht1;2 had a stronger AsV tolerance than PnPht1;1-expressing cells, and accumulated less As in cells under a high-Pi concentration. Combining with the result of plasma membrane localization, these data confirmed that transporters PnPht1;1 and PnPht1;2 were putative high-affinity H+/H2PO4 − symporters, mediating the uptake of Pi and AsV. Conclusion PnPht1;1 and PnPht1;2 encoded functional plasma membrane-localized transporter proteins that mediated a putative high-affinity Pi/H+ symport activity. Expression of PnPht1;1 or PnPht1;2 in mutant strains could enhance the uptake of Pi and AsV, that is probably responsible for the As accumulation in the roots of P. notoginseng.

The crisis of arsenic (As) accumulation in rhizomes threatens the quality and safety of Panax notoginseng (Burk.) F.H. Chen, which is a well-known traditional Chinese herb with a long clinical history. The uptake of arsenate (AsV) could be suppressed by supplying phosphate (Pi), in which Pi transporters play important roles in the uptake of Pi and AsV. Herein, the P. notoginseng Pi transporter-encoding gene PnPht1;3 was identified and characterised under Pi deficiency and AsV exposure. In this study, the open reading frame (ORF) of PnPht1;3 was cloned according to RNA-seq and encoded 545 amino acids. The relative expression levels revealed that PnPht1;3 was significantly upregulated under phosphate deficiency and AsV exposure. Heterologous expression in Saccharomyces cerevisiae MB192 demonstrated that PnPht1;3 performed optimally in complementing the yeast Pi-transport defect and accumulated more As in the cells. Combined with the subcellular localisation prediction, it was concluded that PnPht1;3 encodes a functional plasma membrane-localised transporter protein that mediates putative high-affinity Pi/H+ symport activity and enhances the uptake of Pi and AsV. Therefore, a better understanding of the roles of the P. notoginseng Pi transporter could provide new insight for solving As accumulation in medicinal plants. [ABSTRACT FROM AUTHOR]

Vascular endothelial cells (ECs) at arterial branches and curvatures experience disturbed blood flow and induce a quiescent-to-activated phenotypic transition of the adjacent smooth muscle cells (SMCs) and a subsequent smooth muscle hyperplasia. However, the mechanism underlying the flow pattern-specific initiation of EC-to-SMC signaling remains elusive. Our previous study demonstrated that endothelial microRNA-126-3p (miR-126-3p) acts as a key intercellular molecule to increase turnover of the recipient SMCs, and that its release is reduced by atheroprotective laminar shear (12 dynes/cm²) toECs. Here we provide evidence that atherogenic oscillatory shear (0.5 ± 4 dynes/cm²), but not atheroprotective pulsatile shear (12 ± 4 dynes/cm²), increases the endothelial secretion of nonmembrane-bound miR-126-3p and other microRNAs (miRNAs) via the activation of SNAREs, vesicle-associated membrane protein 3 (VAMP3) and synaptosomal-associated protein 23 (SNAP23). Knockdown of VAMP3 and SNAP23 reduces endothelial secretion of miR-126-3p and miR-200a-3p, as well as the proliferation, migration, and suppression of contractile markers in SMCs caused by EC-coculture. Pharmacological intervention of mammalian target of rapamycin complex 1 in ECs blocks endothelial secretion and EC-to-SMC transfer ofmiR-126-3p through transcriptional inhibition of VAMP3 and SNAP23. Systemic inhibition of VAMP3 and SNAP23 by rapamycin or periadventitial application of the endocytosis inhibitor dynasore ameliorates the disturbed flow-induced neointimal formation, whereas intraluminal overexpression of SNAP23 aggravates it. Our findings demonstrate the flow-pattern--specificity of SNARE activation and its contribution to the miRNA-mediated EC-SMC communication. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that the dysregulation of miRNAs expression is involved in the tumorigenesis by acting as tumor suppressors or oncogenes. However, no study investigates the function and mechanisms of miR-24 in nasopharyngeal carcinoma (NPC). Methods: Quantitative RT-PCR, MTT, colony formation, soft-agar, wound healing, Transwell migration and invasion assays, and xenograft tumor growth and lung metastasis models were performed to test the expression levels and functions of miR-24 in NPC. Luciferase reporter assay, quantitative RT-PCR, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-24. Results: The results showed that MiR-24 was obviously downregulated in NPC cell lines and tissue samples (P < 0.05). Ectopic expression of miR-24 inhibited the cell viability, proliferation, migration, and invasion in vitro (all P < 0.05), and suppressed the xenograft tumor growth and lung metastasis formation in vivo (all P < 0.05). Fascin homologue 1 (FSCN1) was verified as a direct target of miR-24, and silencing FSCN1 expression with small interfering RNA inhibited NPC cell proliferation and invasion (all P < 0.05). Conclusions: Overall, miR-24 acts as a novel tumor suppressor in the development and progression of NPC through targeting FSCN1, which providing new insight into the mechanisms of NPC carcinogenesis and suggesting the possibility of miR-24 as a therapeutic target. [ABSTRACT FROM AUTHOR]

The lipoprotein lipase deficient (LPL–/–) mice and high fat-diet (HFD) induced hypertriglyceridemic mice were used to investigate the effects of cardiotonic pill (CP) on RBC rheologic abnormalities. Mice were randomly divided into the following five groups: the control group; the untreated HFD group; the untreated LPL–/– group; the treated HFD group; and the treated LPL–/– group, and the treated HFD and LPL–/– mice were administered with CP twice a day (400 mg/kg/day) orally for four weeks. Then, plasma triglyceride (TG), RBC deformation index (DI), orientation index (DI)or and RBC electrophoretic time (EPT) were measured. Compared with the untreated HFD mice, TG level and EPT reduced and DI and (DI)or increased markedly in the treated HFD mice (P<0.05). However, compared with the untreated LPL–/– mice, these parameters in the treated LPL–/– mice had no statistically significant changes (P>0.05). Our data show that CP can lower plasma TG level and ameliorate RBC rheologic abnormalities in the HFD-induced hypertriglyceridemic mice, but it losses its capacity in the LPL deficient animals. The results indicate that LPL may be one of the important targets for CP regulating lipometabolism and rheologic abnormalities. [ABSTRACT FROM AUTHOR]

Objective. A combination of vasopressin and epinephrine may be more effective than epinephrine alone in cardiopulmonary resuscitation (CPR), but evidence is lacking to make clinical recommendations. This meta-analysis compares the efficacy of vasopressin and epinephrine used together versus epinephrine alone in cardiac arrest (CA). Methods. We searched MEDLINE and EMBASE for randomized trials comparing the efficacy of vasopressin and epinephrine versus epinephrine alone in adults with cardiac arrest. The primary outcome was the return of spontaneous circulation (ROSC) and the survival rate on admission and discharge. We also analyzed ROSC in subgroups of patients presenting with different arrest rhythms, such as asystole, pulseless electrical activity (PEA), ventricular fibrillation (VF). Results. We analyzed 6 randomized trials out of 485 articles. We did not find evidence supporting the superiority of vasopressin and epinephrine used in combination, except for the survival rate at 24h 2.99 95% CI(1.43,6.28). No evidence supports the conclusion that vasopressin combined with epinephrine is better than epinephrine alone for ROSC, even amongst subgroups of patients. Conclusion. This systematic review of the efficacy of vasopressin and epinephrine use found that its combined use is better for 24h survival rate but only in one study which included 122 patients. Further investigation will be needed to support the use of this combination for cardiac arrest management. [ABSTRACT FROM AUTHOR]