BackgroundA number of studies have implicated the direct involvement of the liver in dengue virus (DENV) infection, and it has been widely shown that liver cells subsequently undergo apoptosis. The mechanism by which liver cells undergo apoptosis in response to DENV infection remains unclear. To provide further information on the mechanism of apoptosis in DENV infected liver cells, HepG2 cells were infected with DENV 2 and analyzed for the induction of ER stress, apoptosis and autophagy.ResultsIn response to DENV infection, HepG2 cells showed the induction of both the ER resident unfolded protein response as well as the Noxa/PUMA stress response pathways. Proteolytic activation of caspases 4, 7, 8 and 9 was observed as well as changes in mitochondrial transmembrane potential. Increased monodansylcadaverine staining was observed in DENV infected cells, consistent with the previously reported induction of autophagy.ConclusionsThese results are consistent with a model in which the induction of multiple ER stress pathways is coupled with the induction of multiple cell death pathways as a mechanism to ensure the removal of infected liver cells from the system.

Pro-inflammatory mediators produced during inflammatory response have been demonstrated to initiate and aggravate pathological development of several chronic diseases. Plant bioactive constituents have been reported to exert anti-inflammatory activities. Various parts of Moringa oleifera have long been used as habitual diets and traditional remedy along the tropical region. Anti-inflammatory activity of boiled M. oleifera pod extract was assessed by measuring pro-inflammatory mediator expression in the lipopolysaccharide-induced murine RAW264.7 macrophage cells. Prior treatment with 31-250 μg/mL M. oleifera extract for 1 h inhibited elevation of mRNA and protein level of interleukine-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenease-2, induced by lipopolysaccharide for 24 h in a dose-dependent manner. The suppressive effect was mediated partly by inhibiting phosphorylation of inhibitor kappa B protein and mitogen-activated protein kinases. These results indicate that the anti-inflammatory activity from bioactive compounds present in the M. oleifera pod constituents may contribute to ameliorate the pathogenesis of inflammatory-associated chronic diseases.

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Suitable diet for cancer survivors remains an unresolved challenge. Increased glucose utilization is a hallmark of various cancers. Therefore, alternative carbohydrate supplying normal tissue but retarding cancer growth is needed. This study investigated the effect of sugar alcohols on the proliferation of oral cancer cells compared to nontransformed cells and explored the mechanism. Six oral squamous cell carcinoma (CAL-27, FaDu, SCC4, SCC9, SCC15, and SCC25) and one nontransformed oral keratinocyte (OKF6/TERT2) lines were cultured in media containing 1 mg/ml glucose and 5.8 mg/ml xylitol or sorbitol, yielding equal energy input to control group (4.5 mg/ml glucose). Partial substitution of glucose with sugar alcohols especially xylitol significantly suppressed proliferation of oral cancer but not nontransformed cells. Despite the addition of isocaloric quantities of the sugars, cancer cells exposed to low glucose plus xylitol had retarded ATP generation and decreased activity of phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis. Furthermore, D-xylulose, its key metabolic intermediate, enhanced the anticancer effect of xylitol. These findings suggested a selective anticancer activity of xylitol and the potential mechanism involving inhibition of glucose utilization. Partial substitution of glucose with xylitol may be a proper nutrient for oral cancer survivors, deserving further investigation in animal and clinical settings.

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BackgroundDue to their extensive self-renewal and multilineage differentiation capacity, human embryonic stem cells (hESCs) have great potential for studying developmental biology, disease modeling, and developing cell replacement therapy. The first hESC line was generated in 1998 by culturing inner cell mass (ICM) cells isolated from human blastocysts using an immunosurgery technique. Since then, many techniques including mechanical ICM isolation, laser dissection, and whole embryo culture have been used to derive hESC lines. However, the hESC derivation efficiency remains low, usually less than 50%, and it requires a large number of human embryos to derive a significant number of hESC lines. Due to a shortage of and restricted access to human embryos, a novel approach with better hESC derivation efficiency is badly needed to decrease the number of embryos used.MethodsWe hypothesized that the low hESC derivation efficiency might be due to extensive proliferation of trophoblast (TE) cells which could interfere with ICM proliferation. We therefore developed a methodology to minimize TE cell proliferation by culturing ICM in a feeder-free system for 3 days before transferring them onto feeder cells.ResultsThis minimized trophoblast cell proliferation (MTP) technique could be successfully used to derive hESCs from normal, abnormal, and frozen–thawed embryos with better derivation efficiency of more than 50% (range 50–100%; median 70%).ConclusionsWe successfully developed a better hESC derivation methodology using the “MTP” culture system. This methodology can be effectively used to derive hESCs from both normal and abnormal embryos under feeder-free conditions with higher efficiency when compared with other methodologies. With this methodology, large-scale production of clinical-grade hESCs is feasible.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0866-5) contains supplementary material, which is available to authorized users.