Association of p53 Codon 72 Polymorphism with Risk of Hypopharyngeal Squamous Cell Carcinoma in Taiwan

Backgroundp53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit.MethodsGenomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism.ResultsPatients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04).ConclusionThis study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer

The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker

The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia

Hypolipidemic Effects of Three Purgative Decoctions

In traditional Chinese medicine (TCM), purgation is indicated when a person suffers an illness due to the accumulation of evil internal heat. Obese individuals with a large belly, red face, thick and yellow tongue fur, constipation, and avoidance of heat are thought accumulates of evil internal heat, and they are also treated with purgatives such as Ta-Cheng-Chi-Tang (TCCT), Xiao-Chen-Chi-Tang (XCCT), and Tiao-Wei-Chen-Chi-Tang (TWCCT) by TCM doctors. In previous studies, our group found that TCCT has potent anti-inflammatory activity, and that XCCT is an effective antioxidant. Since rhubarb is the principle herb in these three prescriptions, we will first present a thorough review of the literature on the demonstrated effect (or lack of effect) of rhubarb and rhubarb-containing polyherbal preparations on lipid and weight control. We will then continue our research with an investigation of the anti-obesity and lipid-lowering effect of TCCT, XCCT, TWCCT, and rhubarb extracts using two animal models. TWCCT lowered the serum triglyceride concentration as much as fenofibrate in Triton WR-1339-treated mice. Daily supplementation with XCCT and TWCCT significantly attenuated the high-fat-diet-induced hypercholesterolemia in rats. In addition, TWCCT also significantly lowered the high-fat-diet-induced hypertriglycemia. Although feeding high-fat diet rats with these extracts did not cause loose stools or diarrhea or other deleterious effects on renal or hepatic function. None of these extracts lowered the body weight of rats fed on high-fat diet. In conclusion, the results suggest that XCCT and TWCCT might exert beneficial effects in the treatment of hyperlipidemia

Induction of apoptosis by the retinoid inducible growth regulator RIG1 depends on the NC motif in HtTA cervical cancer cells

<p>Abstract</p> <p>Background</p> <p>Retinoid-inducible gene 1 (RIG1), also known as tazarotene-induced gene 3 or retinoic-acid receptor responder 3, is a growth regulator, which induces apoptosis and differentiation. RIG1 is classified into the NC protein family. This study investigated functional domains and critical amino acids associated with RIG1-mediated cell death and apoptosis.</p> <p>Results</p> <p>Using enhanced green fluorescence protein (EGFP)-tagged RIG1 variants, RIG1 proteins with deletion at the NC domain significantly decreased cell death induced by RIG1, and fusion variants containing only the NC domain significantly induced apoptosis of HtTA cervical cancer cells. The EGFP-RIG1-induced apoptosis was significantly decreased in cells expressing N¹¹²C¹¹³motif double- (NC→FG) or triple- (NCR→FGE) mutated RIG1 variants. Using dodecapeptides, nuclear localization and profound cell death was observed in HtTA cells expressing wild type RIG1_111–123or Leu¹²¹-mutated RIG1_111–123:L→ C peptide, but peptides double- or triple-mutated at the NC motif alone, RIG1_111–123:NC→FG or RIG1_111–123:NCR→FGE, were cytoplasmically localized and did not induce apoptosis. The RIG1_111–123also induced apoptosis of A2058 melanoma cells but not normal human fibroblasts.</p> <p>Conclusion</p> <p>The NC domain, especially the NC motif, plays the major role in RIG1-mediated pro-apoptotic activity. The RIG1_111–123dodecapeptide exhibited strong pro-apoptotic activity and has potential as an anticancer drug.</p

Antiosteoporotic Activity of Dioscorea alata L. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation

The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes of Dioscorea alata L. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP) and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX) mice. Microcomputed tomography (μCT) analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD), trabecular bone volume/total volume (BV/TV), and trabecular bone number (Tb.N) in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy

RssAB Signaling Coordinates Early Development of Surface Multicellularity in Serratia marcescens

Bacteria can coordinate several multicellular behaviors in response to environmental changes. Among these, swarming and biofilm formation have attracted significant attention for their correlation with bacterial pathogenicity. However, little is known about when and where the signaling occurs to trigger either swarming or biofilm formation. We have previously identified an RssAB two-component system involved in the regulation of swarming motility and biofilm formation in Serratia marcescens. Here we monitored the RssAB signaling status within single cells by tracing the location of the translational fusion protein EGFP-RssB following development of swarming or biofilm formation. RssAB signaling is specifically activated before surface migration in swarming development and during the early stage of biofilm formation. The activation results in the release of RssB from its cognate inner membrane sensor kinase, RssA, to the cytoplasm where the downstream gene promoters are located. Such dynamic localization of RssB requires phosphorylation of this regulator. By revealing the temporal activation of RssAB signaling following development of surface multicellular behavior, our findings contribute to an improved understanding of how bacteria coordinate their lifestyle on a surface

Drumhead Surface States and Topological Nodal-Line Fermions in TlTaSe2

A topological nodal-line semimetal is a new condensed matter state with one-dimensional bulk nodal lines and two-dimensional drumhead surface bands. Based on first-principles calculations and our effective k . p model, we propose the existence of topological nodal-line fermions in the ternary transition- metal chalcogenide TlTaSe2. The noncentrosymmetric structure and strong spin-orbit coupling give rise to spinful nodal-line bulk states which are protected by a mirror reflection symmetry of this compound. This is remarkably distinguished from other proposed nodal-line semimetals such as Cu3NPb(Zn) in which nodal lines exist only in the limit of vanishing spin-orbit coupling. We show that the drumhead surface states in TlTaSe2, which are associated with the topological nodal lines, exhibit an unconventional chiral spin texture and an exotic Lifshitz transition as a consequence of the linkage among multiple drumhead surface-state pockets.Comment: Related papers at http://physics.princeton.edu/zahidhasangroup/index.htm