Bundgaardfreedman1472
Alcohol is a well-recognized hepatic carcinogen. Alcohol is metabolized into genotoxic acetaldehyde in hepatocytes, which is catalyzed by aldehyde dehydrogenase 2 (ALDH2). The detailed underlying mechanisms of alcohol-related hepatocellular carcinoma (HCC) remains unclear, at least partially, due to the absence of appropriate experimental models. Current studies suggest that rodents are not good models of the most common liver diseases that trigger HCC including alcoholic liver injury. We hypothesize that ethanol could induce transformation of immortalized normal liver cells, which may serve as a versatile tool for studying alcoholic HCC. Besides, we believe that knockout of ALDH2 will help to shorten the time course of transformation, as ALDH2 deficiency will significantly increase the accumulation of acetaldehyde in hepatocytes. Using this model, the dynamic changes of carcinogenesis-related molecular events could be easily examined. Furthermore, the transformed cells isolated from soft agar could be inoculated to mice for studying invasion, metastasis, and also for screening prophylactics.
Nonalcoholic fatty liver disease (NAFLD) is a disease of high prevalence without any approved treatment. Nonalcoholic steatohepatitis (NASH) is an advanced phenotype of the disease and the main focus of ongoing clinical trials. Denosumab, a human monoclonal antibody, which binds and inhibits the receptor activator of nuclear factor kappa-B ligand (RANKL), is a licensed medication for postmenopausal, male and glucocorticoid-induced osteoporosis, as well as for metastatic bone disease associated with specific cancers. Hepatic RANKL upregulation has been shown in a transgenic mice model.
We hypothesized that hepatic RANKL upregulation may be associated with hepatic steatosis and inflammation, thus playing a role in the pathogenesis of NAFLD.
If this hypothesis is verified, denosumab, an established anti-osteoporotic medication, may be considered as a candidate for NASH in drug-repurposing studies.
If this hypothesis is verified, denosumab, an established anti-osteoporotic medication, may be considered as a candidate for NASH in drug-repurposing studies.Lack of vascularization results in increased demand for oxygen and creates a defined feature of the tumor microenvironment known as tumor hypoxia. It is well established that in response to hypoxia, hypoxia-inducible factor-1 α (HIF-1α) is induced which is an important factor in angiogenesis, invasion and metastasis. In turn, HIF-1α regulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF). Ascribed to abnormal characteristics of tumor angiogenic networks, antiangiogenic therapy approaches can even worsen the hypoxic condition and can create cancer cells with stemness features. Hence oxygen delivery via perfluorocarbon (PFC) to hypoxic sites seems to result in unstable HIF expression and consequent inactivation of angiogenesis cascade and metastasis and therefore, inhibition of cancer cells stemness.
Previous work suggests provider recommendation improves vaccine delivery. Less examined is the role of practice's front office staff and nurses in vaccine communication. Messaging and communication about vaccines should be consistent across all levels of the pediatric practice.
We distributed surveys to clinicians, nurses, front office staff, and parents of adolescents 11-17years in pediatric and family medicine office practices. We inquired about perceived importance of adolescent vaccines and the use of recommendations to families about receiving vaccines. We also asked front office staff about concerns from families about vaccines as well as vaccine refusal for themselves and their child.
Nurses perceived that the HPV vaccine was less important than the MenACWY and Tdap vaccines (% very important 84% v. 95% and 94%; P<.01). Parents also perceived HPV vaccine as being less important than MenACWY and Tdap vaccines (59% v 68% and 79%; P<.01. Between groups, parents perceived all vaccines as being less important than front office staff. Nurses and clinicians reported using a strong recommendation less often for HPV vaccine compared to the MenACWY and Tdap (70% v 84% and 84%; P<.01 for nurses, and 77% v. 88% and 86%; P<.05 for clinicians). Front office staff were more likely to report concerns from parents about HPV vaccine than from MenACWY and Tdap after the visit is complete.
Parents, front office staff and nurses differ on the importance of vaccines. Interventions to improve vaccine communication and delivery must include all who work in the practice.
Parents, front office staff and nurses differ on the importance of vaccines. Interventions to improve vaccine communication and delivery must include all who work in the practice.Arsenic (As) exposure poses a serious threat to human health. The present study investigated the effects of organic Se on As accumulation, migration, and As bioaccessibility in As-stressed radish. The results showed that organic Se can effectively block the accumulation of As in radish, reduce As bioaccessibility, and promote the conversion of As from inorganic to organic form. The total As content decreased with increasing Se application in raw radish roots, the gastric fraction and the gastrointestinal fraction. Compared to the control (CK) group, the As bioaccessibility in the 24Se treatment of the yeast Se and malt Se groups decreased by 26% and 37%, respectively. These findings provide new comprehensive information for the application of organic Se to alleviate the toxicological effects of As and reduce the health risks of As in edible plants. In the future, it is necessary to carry out a deeper study of the interaction between Se and As through advanced analytical methods.To understand the taste of the Ruditapes philippinarum, 14 novel umami peptides were isolated and identified by gel chromatography, HPLC and UPLC-ESI-QTOF-MS/MS. Separations were combined with sensory evaluations and electronic tongue determinations. The peptide sequences were GRVSNCAA, SEEK, KEMQKN, KSAEN, QIEELEGK, TDVEQEGD, HNESQN, RGEPNND, TGDPEK, KGGGGP, TYLPVH, PAATIPE, GPAGPAGPR and AGAGPTP. All peptides had umami and umami-enhancing qualities, KSAEN and QIEELEGK had higher sensory evaluation than the others, while PAATIPE and HNESQN had the best umami-enhancing taste in a 0.35% MSG solution. Molecular docking of the peptides with T1R1/T1R3 indicated that Ser123, Ser146 and Tyr143 may be important in the interaction of the peptides with T1R3. Arg303, Ser123 and Asp166 appear to be involved in the synergistic effect of umami peptides combined with monosodium glutamate. Fetuin The omission test and the addition test confirmed that the 14 umami peptides contributed to the umami taste of R. philippinarum.