-
Albright Drejer posted an update 1 day, 6 hours ago
0.23641/asha.11984364.We recently performed two studies exploring the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human colorectal cancers from the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in colorectal cancers from Syria. We reveal that 17 (~17%) of 102 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high/intermediate grade invasive carcinomas. These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they might cooperate on the initiation and/or progression of these cancers. Thus, we believe that future studies are necessary to confirm the co-presence of these oncoviruses and their cooperative role in human colorectal carcinogenesis.CTPphosphocholine cytidylyltransferase (CCT) α and CCTβ catalyze the rate-limiting step in phosphatidylcholine (PC) biosynthesis. CCTα is activated by association of its α-helical M-domain with nuclear membranes, which is negatively regulated by phosphorylation of the adjacent P-domain. To understand how phosphorylation regulates CCT activity, we developed phosphosite-specific antibodies for pS319 and pY359+pS362 at the N- and C-terminus of the P-domain, respectively. Oleate treatment of cultured cells triggered CCTα translocation to the nuclear envelope (NE) and nuclear lipid droplets (nLDs) and rapid dephosphorylation of pS319. Removal of oleate led to dissociation of CCTα from the NE and increased phosphorylation of S319. Choline depletion of cells also caused CCTα translocation to the NE and S319 dephosphorylation. In contrast, Y359 and S362 were constitutively phosphorylated during oleate addition and removal, and CCTα-pY359+pS362 translocated to the NE and nLDs of oleate-treated cells. Mutagenesis revealed that phosphorylation of S319 is regulated independently of Y359+S362, and that CCTα-S315D+S319D was defective in localization to the NE. We conclude that the P-domain undergoes negative charge polarization due to dephosphorylation of S319 and possibly other proline-directed sites and retention of Y359 and S362 phosphorylation, and that dephosphorylation of S319 and S315 is involved in CCTα recruitment to nuclear membranes.Background The high cost and insufficient supply of HPV vaccines have substantially slowed their implementation in lower-income countries. This study aimed to assess the incremental cost-effectiveness of two doses of human papillomavirus (HPV) vaccination (bivalent 16/18 vaccine; 2vHPV) compared to a no-vaccination scenario and a three-dose scenario in one province in China.Methods A static Markov model was used to model a lifetime cohort of 100,000 girls aged 12 years at the start of vaccination. A two-dose vaccination schedule was assumed to be non-inferior to a three-dose schedule in terms of vaccine efficacy, and both vaccination schemes were assumed to provide lifelong protection. Incremental costs, health effects and incremental cost-effectiveness ratios were used to measure the outcomes when comparing the different strategies.Results Compared to no vaccination, the incremental cost-effectiveness ratio (Chinese yuan per quality-adjusted life year) of the two-dose vaccination strategy is 12,472, and the 2-dose strategy is calculated to be cost saving relative to the 3-dose vaccination strategy.Conclusions Introducing the 2vHPV vaccine would be highly cost effective at a per-dose vaccine price of CNY 500, which has implications for cervical cancer control in China and other resource-limited countries.The novel coronavirus infection (COVID-19 or Coronavirus disease 2019) that emerged from Wuhan, Hubei province of China has spread to many countries worldwide. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS in the past decades. However, to date, no licensed antiviral treatment or vaccine exists for MERS and SARS. Most of the efforts for developing CoV vaccines and drugs target the spike glycoprotein or S protein, the major inducer of neutralizing antibodies. Although a few candidates have shown efficacy in in vitro studies, not many have progressed to randomized animal or human trials, hence may have limited use to counter COVID-19 infection. This article highlights ongoing advances in designing vaccines and therapeutics to counter COVID-19 while also focusing on such experiences and advances as made with earlier SARS- and MERS-CoVs, which together could enable efforts to halt this emerging virus infection.Background Compared with trivalent influenza vaccines, quadrivalent influenza vaccines are expected to provide wider protection against influenza B virus infections. We developed a novel quadrivalent subunit influenza vaccine which was distinct from the influenza vaccines available on the market in production process. In this research, we evaluated the safety and immunogenicity of the quadrivalent subunit influenza vaccine in animal models.Methods In toxicity assessment, 40 SD rats were randomly assigned to be intramuscularly injected with 1.0 ml of the tested vaccine (33 μg/ml) or 0.9% sodium chloride solution. In irritation assessment, eight rabbits were randomly assigned to receive 0.5 ml of tested vaccine or phosphate buffer solution intramuscularly. Trichostatin A Thirty-two guinea pigs were randomly assigned to be intramuscularly injected with high-dose tested vaccine (0.5 ml), low-dose tested vaccine (0.05 ml), ovalbumin, or 0.9% sodium chloride solution, respectively, for sensitization assessment. In immunogenicity nd two-dose quadri-vaccine groups were comparable to those in the tri-vaccine or mono-vaccine groups for shared influenza strains. However, the GMTs of HI antibodies against H1N1 (P = 0.025) and BV (P = 0.049) at day 42 in one-dose quadri-vaccine group were significantly lower than those in the tri-vaccine or mono-vaccine groups. The GMTs of HI antibodies against H1N1, H3N1, BY, and BV at day 28 and day 42 were comparable between one-dose quadri-vaccine and two-dose quadri-vaccine groups.Conclusions The quadrivalent subunit influenza vaccine was safe and immunogenic in animal models. One dose of the vaccine could elicit a satisfactory antibody response in mice.