Project description:We profiled genome-wide gene expression in nasal scrapes following grass pollen challenge and Prednisone treatment. It was a randomized, double-blind, placebo-controlled, three-period, cross-over trial to evaluate the effects of single oral doses of 10 mg and 25 mg of prednisone on inflammatory mediators measured in nasal exudates after nasal allergen challenge in susceptible individuals with allergic rhinitis. It examined the ability to quantify responses to allergen challenge and resolve dose responsive treatment effects of prednisone.
Project description:Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n = 47) in a weekly dose of 20,000 IU or placebo (n = 47) for a period of three to five years
Project description:Precise control of protein synthesis by engineering sequence elements in 5’ untranslated region (5’UTR) remains a fundamental challenge. To accelerate our understanding of cis-regulatory code embedded in 5’UTR, we devised massively parallel reporter assays from a synthetic mRNA library composed of over one million 5’UTR variants. A completely randomized 10-nucleotide sequence preceding an upstream open reading frame (uORF) and downstream GFP leads to a broad range of mRNA translatability and stability in mammalian cells. While efficient translation protects mRNA from degradation, uORF translation triggers mRNA decay in a UPF1-dependent manner. We also identified translational inhibitory elements in 5’UTR with G-quadruplex as a mark for mRNA decay in the P-body. Unexpectedly, an unstructured A-rich element in 5’UTR, while enabling cap-independent translation, destabilizes mRNAs in the absence of translation. Our results not only expose diverse sequence features of 5’UTR in controlling mRNA translatability, but also reveal ribosome-dependent and -independent mRNA surveillance pathways.
Project description:For patients with unresectable colorectal cancer liver metastases, preclinical studies have shown that after the resistance of cetuximab, the treatment sensitivity can be restored by stopping cetuximab for a period of time. This is called the cetuximab re-challenge. And the circulating tumor DNA (ctDNA) test is reported a biomarker for the efficacy of cetuximab rechallenge. However, there is still no randomized controlled trial for verification. This study aims at patients after the first-line treatment of cetuximab has progressed. After the second-line non-cetuximab treatment has progressed, the effects of re-application of combined with cetuximab and chemotherapy alone are compared to verify the re-challenge effect.
Project description:To determine differential gene expression in peripheral blood of asthmatic individuals undergoing allergen inhalation challenge between early responders (ERs) and dual responders (DRs) following allergen inhalation challenge
Project description:The purpose of this experiment is to elucidate temporal activities and biological processes that can be inferred in response to a 200cGy challenging dose with or without a 10 cGy priming dose in embryonic human fibroblasts The experiment is designed around the human diploid embryonic lung fibroblast cell line WI38 (TP53 proficient), which was grown as a monolayer (2D) under physiological cell culture conditions (3% O2; 10% CO2). Cells are exposed to 2Gy (e.g., the challenge dose) of ionizing radiation (160 kV X-rays) with or without a priming dose of 10cGy (e.g., the adaptive dose) 4 hours prior to the challenge dose. Three biological replicates for each treatment group (e.g., with and without the priming dose) were collected 1, 2, 4 and 8 hours after the challenge dose. The time course was selected on the basis of our prior research on early response to ionizing radiation [1,2]. Purified total cellular RNA was extracted using an RNeasy Mini Kit (Qiagen) and quantified for Affymetrix microarray analysis using Human Gene 1.0 ST Array. Robust multi-array analysis (RMA) was performed to normalize data collected from the different samples. Samples were examined for quality control using the NUSE protocol. Reference [1] Groesser T. et al., Int J of Radiation Research, 2011. 87(7): p. 696-710. Reference [2] Han J. et al., Microscopy, 2010. 241(3): p. 315-326
Project description:The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans. A total of 31 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 8 vaccinated and 10 control animals subjected to a low dose challenge and 6 vaccinated and 7 control animals subjected to a high dose challenge
Project description:The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans. A total of 34 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 9 vaccinated and 9 control animals subjected to a low dose challenge and 7 vaccinated and 9 control animals subjected to a high dose challenge