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Background Our study aims to investigate the effect of colon cancer-associated transcript-1 (CCAT-1) on colon cancer cells' activity and metabolism under different glucose environments in vitro and in vivo. Methods The levels of proliferation, migration, glucose, lactic acid, glucose metabolism-related enzymes, apoptosis genes, epithelial-mesenchymal transition (EMT) marker proteins, and PI3K/Akt/C-MYC pathway in CCAT-1-silenced SW620 cells cultured with different glucose levels were tested. Twenty BALB/C nude mice with hyperglycemia or normal blood sugar were transplanted with CCAT-1-silenced SW620 cells, blood glucose levels, lactic acid, insulin, and volume of transplanted tumor cells, the expression of EMT marker proteins, and PI3K/Akt/C-MYC pathway was detected. Results The levels of proliferation, migration, glucose, lactic acid, LDH-A, PKM2, and HK2 decreased, apoptosis increased in SW620 cells cultured with low glucose or silenced CCAT-1 (P more...

CD8+ T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+ T-cell subsets were confirmed to be closely related to HCV infection such as TCM , TEM , TEM RA, Tc17, and CD8+ Treg. Herein, we report a new subset of interleukin (IL)-17/interferon (IFN)-γ producing CD8+ T (Tc17/IFN-γ) cells that markedly correlate with CD28+ CD244+ cells, IL-17 levels, and HCV RNA in HCV patients. During early treatment with peg-IFN-a2a plus ribavirin, the imbalance of these Tc17/IFN-γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4-week course of treatment with peg-IFN-a2a plus ribavirin and found that the percentage of CD8+ CD28+ CD244+ T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+ CD244+ T cells were the only CD8+ T-cell group that secreted both IL-17 and IFN-γ in this axis and blockade with anti-CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+ CD244+ Tc17/IFN-γ cells may play an important role in persistent HCV infection. more...

The anti-aging activity of marine macroalgae Gracilaria lemaneiformis polysaccharide (GP) on Caenorhabditis elegans was evaluated by observing the lifespan, reproduction, pharyngeal pumping and stress response of worms. Moreover, quantitative fluorescence of polyglutamic acid and nuclear localization of DAF-16 were observed. The results showed that GP treatment enhanced the mean lifespan by over 16.47% and significantly increased the reproduction duration of worm in the high dose group (1000 μg/mL). GP exhibited little potent effects under the thermotolerance and oxidative stress. The number of polyglutamic acid aggregates in three dosage groups decreased by 24.82%, 32.08% and 30.93% (p 0.05) compared to the control. The middle dose group strongly induced DAF-16 nuclear translocation over intermediate and cytosolic localizations compared to the control (p 0.001). It was inferred that GP extended the adult lifespan of wild-type and polyQ nematodes through the insulin pathway DAF-16. more...

As a partner antimalarial for artemisinin drug-based combination therapy (ACT), piperaquine (PQ) can be metabolized into two major metabolites, including piperaquine N-oxide (M1) and piperaquine N,N-dioxide (M2). To better understand the antimalarial potency of PQ, the antimalarial activity of the PQ metabolites (M1 and M2) was studied in vitro (in Plasmodium falciparum strains Pf3D7 and PfDd2) and in vivo (in the murine species Plasmodium yoelii) in this study. The recrudescence and survival time of infected mice were also recorded after drug treatment. The pharmacokinetic profiles of PQ and its two metabolites (M1 and M2) were investigated in healthy subjects after oral doses of two widely used ACT regimens, i.e., dihydroartemisinin plus piperaquine phosphate (Duo-Cotecxin) and artemisinin plus piperaquine (Artequick). Remarkable antiplasmodial activity was found for PQ (50% growth-inhibitory concentration [IC50], 4.5 nM against Pf3D7 and 6.9 nM against PfDd2; 90% effective dose [ED90], 1.3 mg/kg of body weight), M1 (IC50, 25.5 nM against Pf3D7 and 38.7 nM against PfDd2; ED90, 1.3 mg/kg), and M2 (IC50, 31.2 nM against Pf3D7 and 33.8 nM against PfDd2; ED90, 2.9 mg/kg). Compared with PQ, M1 showed comparable efficacy in terms of recrudescence and survival time and M2 had relatively weaker antimalarial potency. PQ and its two metabolites displayed a long elimination half-life (∼11 days for PQ, ∼9 days for M1, and ∼4 days for M2), and they accumulated after repeated administrations. The contribution of the two PQ metabolites to the efficacy of piperaquine as a partner drug of ACT for the treatment of malaria should be considered for PQ dose optimization. more...

The inhibition of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) potentially represents a new treatment option for malaria, as P. falciparum relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors of PfDHODH. The most potent compound, 26, showed high inhibition activity against PfDHODH (IC50 = 23 nM), with >400-fold species selectivity over human dihydroorotate dehydrogenase (hDHODH). The brand-new inhibitor scaffold targeting PfDHODH reported in this work may lead to the discovery of new antimalarial agents. more...

With the decline of oil reserves and production, the gas-to-liquids (GTL) part of Fischer–Tropsch (F-T) synthesis technology has become increasing important. Synthesis gas (H2 + CO) with a stoichiometric ratio (H2/CO) at 2 or ranging from 1 to 2 is generally used in major synthesis-gas-based chemicals production. There are growing interests in the development of an alternative technology, other than the expensive natural-gas-based catalytic process, for cost-effective production of synthesis gas with a flexible hydrogen/carbon monoxide (H2/CO) ratio. Direct production of synthesis gas using coal as a cheap feedstock is attractive but challenging due to its low H2/CO ratio of generated synthesis gas. Three typical U.S. coals of different ranks were tested in a 2.5 in. coal gasifier to investigate their gasification reactivity and adjustability on H2/CO ratio of generated synthesis gas with or without the addition of methane. Tests indicated that lower-rank coals (lignite and sub-bituminous) have higher gas... more...