MAGE-A9, a well-characterized cancer testis antigen (CTA), belongs to a member of melanoma antigen gene (MAGE) family. In human malignancies, aberrant expression of MAGE genes correlated with poor clinical prognosis, increased tumor growth, metastases, and enrichment in stem cell populations of certain cancers. Cancer stem cells (CSCs) have been proposed to contribute to the major malignant phenotypes of liver cancer, including recurrence, metastasis and chemoresistance. However, expression and potential role of MAGE-A9 in liver cancer stem cells (LCSCs) still remain unclear. In the present study, we first analyzed the expression profiling of MAGE family genes in EpCAM+ and EpCAM- human hepatocellular carcinoma (HCC), based on public Gene Expression Omnibus (GEO) database. Among these examined MAGE members, MAGE-A9 is the only one with significantly higher expression in EpCAM+ HCC specimens as compared with EpCAM- HCC. Quantitative PCR analysis further confirmed that MAGE-A9 expression significantly elevated in a subtype of HCC patients that had features of hepatic stem/progenitor cells with high-level expression of EpCAM and α-fetoprotein (AFP). Moreover, MAGE-A9 displayed remarkably enriched expression in EpCAM+ HCC cells that were sorted by fluorescence-activated cell sorting and cultured HCC cell spheroids with characteristics of stem/progenitor cells. Functional experiments further revealed that MAGE-A9 overexpression promoted cell proliferation, colony formation, migration, chemoresistance, and tumorigenicity in the context of EpCAM+ HCC cells, whereas MAGE-A9 knockdown significantly inhibited anchorage-dependent and spheroid colony formation and in vivo tumorigenicity. Collectively, these data demonstrate that MAGE-A9 functions as an important regulator of LCSCs, and MAGE-A9 may serve as a potential therapeutic target against HCC stem/progenitor cells.
The present study analyzed the presence of human Torque Teno virus (TTV) in hospitalized patients from different departments. In total, 378 serum specimens were collected from the patients (171 with cardiovascular disease, 192 with tumor and 15 with gastroenteritis) and analyzed by ELISA and nest-polymerase chain reaction (PCR) to detect the presence of TTV. The results showed that 64 specimens (17%) were TTV positive from detection with the human ELISA kit, and the patients aged <30 years have a higher prevalence. TTV in males was more common than in female patients. In addition, nest-PCR was used to detect TTV within different phylogenetic groups among the 64 specimens, and the results showed that groups 1 (TA278 strain), 4 (KC009) and 5 (CT39) were much more prevalent than groups 2 (PMV isolate) and 3 (11 genotypes) in the different departmental patients.
Abstract-This paper describes the design of a sampling holder, Using a higher linearity bootstrapped switch, by using the bottom plate sampling to offset the effect of charge injection effect, By using the capacitance flip type structure to reduce power consumption, designing a high gain and high speed operational trans-conductance amplifier to improve gain and speed.
Background: Cerebrospinal fluid (CSF) shunt intervention is currently the standard and most effective treatment for idiopathic normal-pressure hydrocephalus (iNPH). However, many patients do not undergo surgery due to various reasons. The study aimed to assess the efficacy and safety of methazolamide (MTZ) in the treatment of iNPH.
Methods: A 12-week randomized, double-blind, drug-placebo clinical studywas conducted at the Aviation General Hospital. Participants with a diagnosis of possible or probable iNPH according to Japanese second iNPH guidelines were consecutively recruited from September 2019 to May 2021. All patients were inoperable or had refused surgical treatment due to various reasons. The patients were assigned (2:1) to the MTZ or placebo group via a computer-generated randomization list. The gait and cognition function were assessed, and brain MRI scans were taken before and 12 weeks after drug administration. The primary endpoint was the difference change in the Boon gait sum score relative to baseline between the drug and placebo groups. Secondary endpoints were differences in MMSE and MOCA scores. In addition, the adverse reactions were also monitored.
Results: Twenty participants were randomly included in the MTZ group and 12 in the placebo group. A total of 26 patients, 17 in the MTZ and 9 in the placebo group, were included in the final efficacy analysis. The difference in Boon sum score relative to baseline between the groups was -6.06 points (95% CI, -9.37 to -2.75; p =0.001) after 12 weeks of treatment. However, there was no significant difference in the MMSE and MoCA scores between the drug and placebo groups (MMSE 0.36, 95% CI, -2.36 to 3.09; p = 0.78; MoCA 0.001, 95% CI, -1.98 to 1.98; p = 1.00). No serious adverse reactions such as hypokalemia or acidosis occurred in any of the patients.
Conclusions: MTZ significantly improved the gait of iNPH patients without any adverse effects. Large sample studies are needed for further confirmation of our results.
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