HIF-dependent gene regulation was performed by a dual reporter gene assay, using a firefly luciferase construct and a reference Renilla luciferase construct pRL-TK (Promega, Madison, WI). A putative promoter of miR-322 containing the consensus sequence of the HRE was constructed by PCR from rat genomic DNA by using the primers: 5- CCG CTC GAG TAC TTA GTT TAA CTA CAG ACT C -3 (forward) and 5- CGA CGC GTG GGG CCG CTC TGG GGT ACC TGC -3 (reverse). Luciferase activity was measured in cell extracts with a Lumat LB9508 luminometer (Berthold, Bad Wildbad, Germany).

Ghosh et al. have reported that human miR-424, the homolog of rodent miR-322, stabilizes HIF-1α leading to its accumulation in the nucleus in human umbilical vein endothelial cells (HUVEC)23. Therefore, we determined whether manipulating miR-322 expression could affect the levels of HIF-1α in rat PASMCs. Cells were transfected with recombinant lentivirus expressing miR-322 (miR-322), or no miRNA sequence as a negative control (miR-Con). Stably transfected cells were generated by puromycin selection. As shown in Fig. 4a, exposure to hypoxia induced HIF-1α accumulation in the nucleus of PASMCs. qRT-PCR revealed an over 12-fold increase in miR-322 in the cells overexpressing miR-322 compared with control cells (Fig. 4b). Western blot showed that the accumulation of HIF-1α increased in the nucleus when overexpressing miR-322 in normoxia (Fig. 4c). Cells were also transfected with dTud constructs for miR-322 knockdown studies. As shown in Fig. 4b, cells with miR-322 inhibition (anti-322) exhibited significantly reduced expression in miR-322 compared to its control cells (anti-Con). Knockdown of miR-322 abolished the stabilization of HIF-1α in PASMCs under hypoxic condition (Fig. 4c). Taken together these results indicate that hypoxia-induced miR-322 is involved in regulating the stability of HIF-1α in PASMCs.

Hi P.D. I read your book, Dumping Iron, and have to say that many of your thoughts there make a great deal of sense. The idea that many of the beneficial effects of ASA could be due to slow blood loss and the resultant decrease in ferritin levels is both clever and original. It fits with even the latest evidence that ASA takes 5 years or more to give protection. It also makes sense in pre-menopausal women who have low ferritin and low heart disease, but this protection disappears in menopausal women who no longer bleed. Estrogen clearly wasn’t the answer. Well done

What began as a single case has snowballed into a major risk-assessment puzzle. The European Medicines Agency (EMA) is considering not only valsartan and losartan, but candesartan, irbesartan, and olmesartan in its efforts to find root cause (7). Both FDA and the General European Official Medicines Control Laboratories Network (GEON) published methods

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Anesiva, Inc. (NasdaqGM: ANSV ) Anesiva, Inc. seeks to be a leader in the development of novel pharmaceutical products for pain management. The company’s lead product candidate is Adlea, a novel small molecule formulation of capsaicin that is currently in development for the management of acute pain following orthopedic surgeries. Adlea has been shown in ACTIVE-2 and in previous clinical trials to provide well-tolerated and extended pain relief after only a single administration in multiple indications for site-specific, acute and chronic, moderate-to-severe pain.

        We initiated a Phase 2 clinical trial with zilucoplan for gMG in the fourth quarter of 2017. In December 2018, we announced positive top-line results from our Phase 2 clinical trial evaluating zilucoplan for the treatment of gMG. The Phase 2, multi-center, randomized, double-blind, placebo-controlled trial was designed to evaluate the safety, tolerability, and preliminary efficacy of zilucoplan in patients with gMG, regardless of prior therapies, who had a Myasthenia Gravis Foundation of America, or MGFA, Disease Class of II-IVa at screening, and a Quantitative Myasthenia Gravis, or QMG, score of at least 12 at screening and randomization.

Genetic Technologies (ASX:GTG.AX ; NASDAQGM: GENE ) specializes in licensing, genetic testing and research. GTG’s exclusive access to a wide range of genetic tests enables it to expand its testing services throughout the Asia-Pacific region. GTG’s pipeline of innovative research projects will potentially add considerable value to its licensing and genetic testing businesses.

This service supports our customers’ needs and shortens time-to-market: from research grade chemicals and peptide custom synthesis, to custom synthesis of complex organic molecules, GMP peptide manufacturing of NCEs, and generic peptides and peptides in their finished dosage form.

Li, J. et al. Inhibition of p38 mitogen-activated protein kinase and transforming growth factor-beta1/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy. The American journal of pathology. 169, 1527–1540 (2006).

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