Hepatocellular carcinoma (HCC) is a frequent cause of cancer-related death; therefore, more effective anticancer therapies for the treatment of HCC are needed. Histone deacetylase (HDAC) inhibitors serve as promising anticancer drugs because they can induce cell growth arrest and apoptosis. We previously reported that 3-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-5-yl]-N-hydroxyacrylamide (MPT0G009)—a novel 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines compound—demonstrated potent pan-HDAC inhibition and anti-inflammatory effects. In this study, we evaluated the anti-HCC activity of MPT0G009 in vitro and in vivo. Growth inhibition, apoptosis, and inhibited HDAC activity induced by MPT0G009 were more potent than a marketed HDAC inhibitor SAHA (Vorinostat). Furthermore, MPT0G009-induced apoptosis of Hep3B cells was characterized by an increase in apoptotic (sub-G1) population, loss of mitochondrial membrane potential, activation of caspase cascade, increased levels of pro-apoptotic protein (Bim), and decreased levels of anti-apoptotic proteins (Bcl-2, Bcl-xL, and FLICE-inhibitory protein); the downregulation FLIP by MPT0G009 is mediated through proteasome-mediated degradation and transcriptional suppression. In addition, combinations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with lower concentrations (0.1 μM) of MPT0G009 were synergistic in cell growth inhibition and apoptosis in HCC cells. In the in vivo model, MPT0G009 markedly reduced Hep3B xenograft tumor volume, inhibited HDAC activities, and induced apoptosis in the Hep3B xenografts. Our results demonstrate that MPT0G009 is a potential new candidate drug for HCC therapy.

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Objective: To evaluate the safety and effectiveness of overnight orthokeratology lenses with Roflufocon E, a highly gas-permeable lens material, for the temporary and reversible correction of myopia.Methods: Myopic individuals from 9 to 45 years of age were eligible for inclusion in the study. Participants ≤12 years of age were required to have myopia between -1.00~-4.00D and astigmatism ≤-1.50D, and for those 13-45 years of age myopia between -1.00~-6.00D and astigmatism ≤-1.50D. All participants were required to have normal, healthy eyes and not be receiving any ocular medications or systemic medications likely to affect the results of visual acuity.Each participants wore the lenses for 8 to 9 hours while asleep, and they were evaluated on day 1 and weeks 1, 2, 4, 8, 12, 24, and 36. Success was defined as uncorrected visual acuity (UCVA) ≥ 0.8(0.1LogMAR). Orthokeratology wear was discontinued after the week 36 visit. There then followed a further three follow-up visits on day 1 and weeks 1 and 4 after the final evaluation visit.Results: A total of 85 participants (67.1% male) with a mean age of 15.9 ± 6.87 years were recruited. Baseline UCVA were 0.18±0.16(0.76±0.25LogMAR) for the ≤-4.00D group and 0.06±0.07(0.95±0.11LogMAR) for the >-4.00D group. A consistent increase in UCVA was noted from day 1 to week 36. The success rate increased with length of time. The success rates were 99.0% and 95.7% in the <-4.00 and >-4.00 groups respectively, from day1 to week 36. No severe complications were noted. Conclusion:The safety and efficacy study outlined here shows orthokeratology to be a safe and effective way to control myopia. Wearing orthokeratology long-term can profoundly reduce myopia, with excellent UCVA during the day, and is applicable to teenagers in controlling myopia.

NMDA receptors are involved in central nerve conduction and are distributed in the forebrain, pituitary gland, hypothalamus, and marginal lobe systems. They are the basic mechanisms of memory and learning.