Recent studies of muscle-invasive bladder cancer show that FGFR3 mutations are generally found in a luminal papillary tumour subtype that is characterised by better survival than other molecular subtypes. To better understand the role of FGFR3 in invasive bladder cancer, we examined the process of tumour development induced by the tobacco carcinogen OH-BBN in genetically engineered models that express mutationally activated FGFR3 S249C or FGFR3 K644E in the urothelium. Both occurrence and progression of OH-BBN-driven tumours were increased in the presence of an S249C mutation compared to wild-type control mice. Interestingly, at an early tumour initiation stage, the acute inflammatory response in OH-BBN-treated bladders was suppressed in the presence of an S249C mutation. However, at later stages of tumour progression, increased inflammation was observed in S249C tumours, long after the carcinogen administration had ceased. Early-phase neutrophil depletion using an anti-Ly6G monoclonal antibody resulted in an increased neutrophil-to-lymphocyte ratio at later stages of pathogenesis, indicative of enhanced tumour pathogenesis, which supports the hypothesis that suppression of acute inflammation could play a causative role. Statistical analyses of correlation showed that while initial bladder phenotypes in morphology and inflammation were FGFR3-dependent, increased levels of inflammation were associated with tumour progression at the later stage. This study provides a novel insight into the tumour-promoting effect of FGFR3 mutations via regulation of inflammation at the pre-tumour stage in the bladder. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
BackgroundThe Malaysian Tualang honey (TH) is not only cytotoxic to human breast cancer cell lines but it has recently been reported to promote the anticancer activity induced by tamoxifen in MCF-7 and MDA-MB-231 cells suggesting its potential as an adjuvant for the chemotherapeutic agent. However, tamoxifen produces adverse effects that could be due to its ability to induce cellular DNA damage. Therefore, the study is undertaken to determine the possible modulation of the activity of 4-hydroxytamoxifen (OHT), an active metabolite of tamoxifen, by TH in non-cancerous epithelial cell line, MCF-10A, in comparison with MCF-7 cells.MethodsMCF-7 and MCF-10A cells were treated with TH, OHT or the combination of both and cytotoxicity and antiproliferative activity were determined using LDH and MTT assays, respectively. The effect on cellular DNA integrity was analysed by comet assay and the expression of DNA repair enzymes was determined by Western blotting.ResultsOHT exposure was cytotoxic to both cell lines whereas TH was cytotoxic to MCF-7 cells only. TH also significantly decreased the cytotoxic effect of OHT in MCF-10A but not in MCF-7 cells. TH induced proliferation of MCF10A cells but OHT caused growth inhibition that was abrogated by the concomitant treatment with TH. While TH enhanced the OHT-induced DNA damage in the cancer cells, it dampened the genotoxic effect of OHT in the non-cancerous cells. This was supported by the increased expression of DNA repair proteins, Ku70 and Ku80, in MCF-10A cells by TH.ConclusionThe findings indicate that TH could afford protection of non-cancerous cells from the toxic effects of tamoxifen by increasing the efficiency of DNA repair mechanism in these cells.
Yogurt enriched with probiotic bacteria benefits health by strengthening the abdominal ecosystem. A short shelf-life and poor survivability of probiotic in yogurt remains a great problem in production and manufacturing processes. Cell immobilization is believed as a suitable way to lengthen the probiotic survivability and prolong yogurt shelf-life. One of the cheap sources of natural immobilization carrier is okara, a soybean by-product. Due to its overproduction, the okara is becoming a source of pollution. The use of okara as a food additive in dairy products such as yogurt is potentially one strategic approach to minimize pollution. Therefore, this study has evaluated the effect of fortification with increasing concentrations of okara on texture, probiotic survivability, nutritive value, and sensory qualities of yogurt. On day 1, the yogurt fortified with 1% okara was the most preferable to panelists because of its high texture consistency, the lightest color, more sour taste, low sugar and fat contents, and high viability of probiotic bacteria. Based on this finding, we suggested 1% okara is the best formulation for symbiotic yogurt production.
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or mostly known as COVID-19, has infected millions of people and led to a public health crisis. Various aspects including the economy and daily routine of life have also been severely affected. At the time being, treatment using previously FDA-approved antiviral such as hydroxychloroquine and remdesivir, as well as using convalescent plasma does not guarantee full recovery of COVID-19 infection. Thus, the search for effective treatment against COVID-19 is actively going on including using natural products. Bee products such as honey (with trehalulose sugar), propolis, royal jelly, bee pollen, and bee bread, are among the natural products that hold promises in attenuating COVID-19, either as an alternative source of the antiviral activity or to enhance the activity of current standard ward treatments. Besides being used in the human diet since ancient times, numerous pre-clinical and clinical studies have shown their pharmacological activities in improving general well-being as well as reducing the risk of developing various diseases. This review will consider a range of honey bee and stingless bee products and evaluate the evidence available for their therapeutic potential against COVID-19 infection. Here, we review the biological properties of bee products and evaluate the evidence available for their therapeutic potential in reducing the risk of developing COVID-19 as well as curing it.
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