Clancyvoss5732

Maintenance on topiramate and phentermine alone significantly decreased cocaine self-administration although these effects were modest in magnitude. Combining topiramate and phentermine robustly decreased cocaine self-administration. Topiramate and phentermine were well tolerated alone and combined, as well as in conjunction with cocaine.

The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.

The results of the present study support advancing topiramate-phentermine combinations as a putative pharmacotherapeutic for cocaine use disorder.Clinically, acute cerium dioxide poisoning or damage is very rare. Here, the investigator reported a case about the patient who accidental ingested cerium dioxide nanoparticles during work shift. The patient recovered well after the treatment with removal of cerium and restoring coagulation factor activity. The author also reviewed relative literatures to discuss the potential mechanism of coagulation disorders following cerium dioxide nanoparticles ingestion. TI17 This case is the first report in the world about acute oral poisoning due to cerium dioxide nanoparticles, with the exact exposure concentration.In the present study, we have investigated the effects of three (elutriate, polar and non-polar) different soil extraction methods from the Lemna solid waste dumpsite (Calabar, Nigeria) on the biotransformation, antioxidant and cellular defense responses of PLHC-1 cell line. Following a 48 h exposure period to different concentrations of each extract, the PLHC-1 cells were evaluated for enzymatic activities - glutathione peroxidase (Gpx), glutathione reductase (Gr), glutathione S-transferase (Gst), 7-ethoxy-, pentoxy-, and benzyloxyresorufin O-deethylase (EROD, PROD and BROD) and mRNA expressions for catalase (cat), gpx, gst, cyp1a, cyp3a, mammalian target of rapamycin (mtor), nuclear factor erythroid 2-related factor 2 (nrf2) and Kelch-like erythroid cell-derived protein (keap-1). Overall, our results showed parameter-, extract- and concentration-specific increases in transcripts and functional product levels for biotransformation, antioxidant and cellular defense/cytoprotective responses, compared with contediments, for ecotoxicological monitoring programs.Liver cancer is of the devastating human cancers and its incidence is increasing at an alarming rate. The clinical outcomes are far from descent due to lack of efficient therapeutic targets and chemotherapeutic agents. Studies have revealed the therapeutic implications of microRNAs in the management of different human cancers. This study was designed to explore the role and therapeutic potential of miR-638 in liver cancer via modulation of zeste homolog 2 (EZH2). The results revealed significant (P less then 0.05) downregulation of miR-638 in human liver cancer tissues and cell lines. Overexpression of miR-638 led to a significant (P less then 0.05) decline in liver cancer cell proliferation. Nonetheless, inhibition of miR-638 could promote the proliferation of the human liver cancer cells. The DAPI and annexin V/PI staining assays revealed that miR-638 induces apoptosis in human liver cancer cells which was accompanied by enhancement of Bax and depletion of Bcl-2 expression. Furthermore, miR-638 overexpression also leads to a significant (P less then 0.05) increase of autophagosomes and autolysosomes in liver cancer cells suggestive of autophagy. The induction of autophagy was further confirmed by increase and decrease in expression of LC3B-II and Beclin-1 proteins, respectively. In contrary, inhibition of miR-638 prevented both apoptosis and autophagy of the liver cancer cells. In silico analysis and the dual luciferase assay revealed EZH2 as the molecular target of miR-638 at post-transcriptional level. The qRT-PCR showed that EZH2 to be significantly (P less then 0.05) upregulated in the human liver cancer tissues and cell lines. However, the expression of EZH2 was considerably suppressed upon miR-638 overexpression in SNU-423 cells. Taken together, these findings suggest the tumor-suppressive role of miR-638/EZH2 axis liver cancer and point towards the potential of miR-638 as therapeutic target in the treatment of liver cancer.We investigated the feasibility of densely polyethylene glycol (PEG2000)-modified liposomes as mucus-penetrating particles (MPPs) for oral delivery of systemically absorbed peptides. The oral absorption of MPPs and mucoadhesive liposomes modified with glycol chitosan (GCS) was compared. In an in vitro artificial mucus model, the densely PEGylated liposomes showed mucus permeability. Intracellular uptake of liposomes was evaluated in a Caco-2 and mucus-secreting Caco-2/HT29 co-culture. Intracellular uptake of MPPs was unaffected by mucus in the co-culture system, whereas the cellular uptake of GCS-liposomes was lower with a mucus layer than in Caco-2 alone. Rat in vivo oral absorption of liposomes was evaluated by using fluorescein isothiocyanate dextran (FD) as a model peptide drug. Oral absorption was higher for densely PEGylated than for unmodified liposomes and was PEG-concentration dependent, but excessive PEGylation decreased FD blood concentration. PEGylated liposomes incorporating spermine (SPM) as an absorption enhancer were then designed and showed the highest in vivo absorption of FD of all tested formulations. The pharmacological effects of the oral liposomes were evaluated by using elcatonin and did not correlate with FD oral absorption. The non-PEGylated SPM liposomes showed the highest pharmacological effect, suggesting the need for drug-specific optimization of liposomal components and surface modifiers.Ionizing radiation is a conventional therapy for cancer patients, but patients often experience distant metastasis and recurrence, which lead to a poor prognosis after the implementation of this treatment. Moreover, the underlying mechanisms by which radioresistance contributes to metastatic potential is still elusive. Here, we explored the molecular mechanisms that contribute to radioresistance in bladder cancer. To achieve this, we established two irradiation-resistant (IR) cell lines, T24R and 5637R, which were derived from parental bladder cancer cell lines. Cell viability was detected by CCK-8 assay, while migration and invasion abilities were examined by wound healing and Transwell chamber assays, respectively. Furthermore, the role of Cdc20 in the regulation of epithelial to mesenchymal transition (EMT) in IR cells was explored by Western blotting, immunoprecipitation and immunofluorescence staining. The IR cells exhibited EMT properties, and our data showed that Cdc20 expression was significantly elevated in IR cells.