Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second major cause of cancerous deaths in the world, accounting for 80-90% of all cases of liver cancer with an assessed global incidence of 782,000 new cases and approximate 746,000 deaths in 2012. Preoperative laboratory data (des-γ carboxyprothrombin (DCP), α-fetoprotein (AFP), Indocyanine green retention 15 min (ICG-R15), and γ-glutamyl transferase (GGT)) should be completely assessed before deciding a treatment and predicting prognosis in order to improve the prognosis for patients with HCC. A few recent studies have suggested GGT as an independent prognostic indicator in cases with HCC. And the data of our and other research teams revealed that combination of GGT and ICG-R15 or other factors may improve the efficiency of GGT as a prognostic predictor. In addition of clinical studies, a few mechanistic studies had been performed and GGT was suggested to promote tumor progression and poor prognosis through inducing DNA damage and genome instability, releasing reactive oxygen species to activating invasion-related signaling pathway, blocking chemotherapy, regulating microRNAs, and managing CpG island methylation. Although there were a few mechanistic studies, further and accurate researches were still in need.
In this study, a series of novel scaffold-based 3-(((substituted phenyl)amino)methyl)-2-methylquinazolin-4(3H)-one compounds, 3a-3r, was synthesized, characterized, and screened for its in vitro activity against the H37Ra strain of Mycobacterium tuberculosis. A number of analogs were found to have highly potent anti-tuberculosis activity. Compound 3m in particular had potent activity equal to that of the standard anti-tuberculosis drug rifampicin. New leads can be generated with the model developed in this study and this model will be optimized with the eventual goal of preparing new anti-tuberculosis agents.
Human Embryonic Lung fibroblasts (HEL cells) are widely used as a normal cell in studies of cell biology and can be easily maintained in the resting phase. Here we aimed to discover compounds that exhibit cytotoxicity against HEL cells in the dividing phase, but not in the resting phase. The cytotoxicity of each compound against HEL cells either in the resting phase or in the dividing phase was determined by MTT assay. Ratios of the IC50 of cells in the resting phase and that of cells in the dividing phase (RRD) for these compounds were compared. We selected 44 compounds that exhibited toxic effects on HEL cells in the dividing phase from a chemical library containing 325 anticancer drugs and enzyme inhibitors. The RRD values of those compounds were widely distributed. Paclitaxel and docetaxel, which are clinically used as anticancer drugs, had RRD values larger than 2000. On the other hand, the RRD value of dimethyl sulfoxide, an organic solvent, was 1. The cytotoxic effect of paclitaxel on HEL cells in the dividing phase was attenuated by aphidicolin, hydroxyurea, and nocodazole, confirming that the cytotoxic effects of paclitaxel are dependent on cells being in the dividing phase. Thapsigargin, whose RRD value was 800, the third highest RRD value in the library, exhibited therapeutic effects in a mouse model of FM3A ascites carcinoma. We suggest that compounds with high RRD values for HEL cells are candidate anticancer chemotherapy seeds.
Influenza A and B virus infections are serious public health concerns globally. However, the concerns regarding influenza B infection have been underestimated. The currently used anti-influenza drugs have not provided equal efficacy for both influenza A and B viruses. Susceptibility to neuraminidase (NA) inhibitors has been observed to be lower for influenza B viruses than for influenza A viruses. Moreover, the emergence of resistance to anti-influenza drugs underscores the need to develop new drugs. Recently, we reported that methylglyoxal (MGO) suppressed influenza A virus replication in a strain-independent manner. Therefore, we hypothesize that MGO exhibits anti-influenza activity against B strains. This study aimed to evaluate the anti-influenza viral activity of MGO against influenza B strains by using Madin-Darby canine kidney (MDCK) cells. Several types of influenza B viruses were used to determine the activity of MGO. The susceptibilities of influenza A and B viruses to NA inhibitors were compared. MGO inhibited influenza B virus replication, with 50% inhibitory concentrations ranging from 23-140 μM, which indicated greater sensitivity of influenza B viruses than influenza A viruses. Our results show that MGO has potent inhibitory activity against influenza B viruses, including NA inhibitor-resistant strains.
Antibody drug conjugates (ADC) are important next-generation biopharmaceuticals and thus require stringent structure characterization as is the case for monoclonal antibodies. We have tested several biophysical techniques, i.e., circular dichroism, analytical ultracentrifugation, differential scanning calorimetry and fluorescence spectroscopy, to characterize a fluorescein-labeled monoclonal antibody as a model ADC. These techniques indicated possible small structure and stability changes by the conjugation, while largely retaining the tertiary structure of the antibody, consistent with unaltered biological activities. Thus, the above biophysical techniques are effective at detecting changes in the structural properties of ADC.
The objective of this study was to explore the relationship between carbohydrate metabolism and the number of steps walked daily, as evaluated by accelerometer, among Japanese women in the second trimester of pregnancy. This longitudinal study was conducted at a university hospital in Tokyo, Japan, from August 2012 to January 2013. Healthy pregnant women at 14 to 18 gestational weeks were recruited. Participants wore accelerometers on the waist for 4 weeks. Casual glucose and hemoglobin A1c (HbA1c) levels were compared between two groups based on whether participants habitually walked ≥ 6,000 steps/day or < 6,000 steps/day. Fifty-one pregnant women were included in the present study; data from 35 were analyzed. There were 22 women in the group that habitually walked ≥ 6,000 steps/day and 13 in the group habitually walking < 6,000 steps/day. Although the median serum casual glucose level at the end of the investigation was 90.0 mg/dL in the group walking < 6,000 steps/day, the level in the group walking ≥ 6000 steps/day was 83.5 mg/dL (p = 0.01). HbA1c levels were not significantly different between the two groups. Our results suggest that walking as a daily habitual physical activity is effective for controlling casual glucose levels in the second trimester of pregnancy.
Biotin responsive basal ganglia disease (BBGD), is a potentially treatable inherited metabolic disorder which clinically presents as sub-acute encephalopathy in children. Early diagnosis and treatment of this disorder results in good clinical recovery in childhood. However, there is no report in the literature on the long term outcome of these treated patients in adult life. We report two patients with BBGD who were metabolically stable on treatment and developed depression later in life. These cases highlight the association of depression with basal ganglia disorders and demonstrate that depression is the potential long term complication of BBGD.
Biobanking entails large-scale collection of human biological specimens that are linked to the donors' health and personal information, and has several applications in clinical research. Human biological specimens, such as blood, urine and tissue, have become immensely important to medical research: they offer a valuable source of genetic material that researchers can use to identify disease-associated genetic variation and to determine interactions between genes and environmental factors. Identification of genetic contributions to disease can lead to the development of new diagnostic tests and targeted treatments. Over the last decade, both common diseases and rare genetic disorders have been reported in Saudi Arabia. The need to generate extensive genetic data on these diseases has led to the establishment of several Saudi Arabian biobanks. Fortunately, these vital efforts have the support of the Saudi Government and researchers. However, the success of any biobank also requires public support and the willingness of the population to donate their biological material along with information on their medical records. Thus, the Saudi public needs to be informed of the benefits of maintaining biobanks, their participation needs to be encouraged through donation of biological material, and any public concerns regarding the confidential treatment of medical data need to be addressed. This article reviews the most common genetic diseases identified in the Saudi population, it describes biobanks and it examines how biobanks can support biomedical research in the area. Moreover, this article proposes measures that might help to increase public awareness of biobanks and the preparedness of the Saudi Arabian population to donate biological material.