Objectives-Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective of this study was to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary liver cancer and their possible effect modifications on various environmental risk factors.Methods-A population-based case-control study was conducted in Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques.Results-The frequency of MTHFR 677 C/C wild homo-zygotes genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratios (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06-2.61), 1.21(95% CI: 0.65-2.28) respectively when compared with the MTHFR 677 C/C genotype. Subjects carrying any T genotype have the increased risk of 1.55(95% CI: 1.01-2.40) for development of primary hepatocellular carcinoma. A high degree of linkage disequilibrium was observed between the C677T and A1298C polymorphisms, with the D′ of 0.887 and p < 0.01. The MTHFR 677 any T genotype was suggested to have potentially more than multiplicative interactions with raw water drinking with p-value for adjusted interaction of 0.03. Conclusion-We observed that the MTHFR 677 C/T genotype was associated with an increased risk of primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might modify the effects of raw water drinking on the risk of primary hepatocellular carcinoma.
Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems and involved in a number of pathophysiological conditions, including pulmonary arterial hypertension, autoimmune and psychiatric disorders, in which it is thus a valuable drug target. Here, we report the cryo-electron microscopy structure of the human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein. Different from all reported peptide-bound class B1 GPCR structures, the N-terminal α-helix of VIP2R adopts a unique conformation that deeply inserts into a cleft between PACAP27 and the extracellular loop 1, thereby stabilizing the peptide-receptor interface. Its truncation or extension significantly decreased VIP2R-mediated cAMP accumulation. Our results provide additional information on peptide recognition and receptor activation among class B1 GPCRs and may facilitate the design of better therapeutics.
Rosin was reacted with hydroxyethyl methacrylate to produce a macromonomer. This macromonomer was used to partly replace styrene for the novel preparation of polymer microspheres with divinylbenzene via suspension polymerization. Orthogonal experiments were conducted to analyze the factors influencing the particle size, particle size distribution, swelling ratio and degree of crosslinking of the polymer microspheres. Fourier transform IR spectroscopy, thermogravimetry and scanning electron microscopy were used to examine the structures, thermal properties and morphologies, respectively, of the polymer microspheres. The results showed that the amount of dispersant had the greatest influence on particle size and distribution. On the other hand, the monomer ratio greatly influenced the swelling ratio and degree of crosslinking of the polymer microspheres. The decomposition temperature of the polymer microspheres increased upon introduction of the rosin moiety into the product. Open pores were abundant on the surface of the polymer microspheres due to the existence of the porogen, which provided a base for adsorption and separation. The present study opens a novel route for using naturally occurring rosin. Copyright © 2012 Society of Chemical Industry
Reacting acrylic rosin with 2-hydroxyethyl methacrylate (HEMA) produced an ester (acrylic rosin ester, RAH) with double bonds that was used as a cross-linking monomer for the preparation of polystyrene microspheres through suspension polymerization, replacing the traditional monomer divinyl benzene. The effects of monomer weight ratio, reaction temperature, gelatin level, and stirring speed on the polymer microspheres were investigated. The structures, morphologies , and properties of the polymer microspheres were analyzed and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, optical microscopy, and laser particle size analysis. The results indicated that the polymer microspheres with the best spherical shape were prepared with a monomer weight ratio of m St/m RAH = 2:1, with azodiisobutyronitrile and gelatin in the amounts of 1 and 6 wt % of total monomers. The particle size of the polymer microspheres varied with the reaction conditions.
Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and relaxin/insulin-like peptides. The latter bind to the human relaxin family peptide receptors (RXFPs). Here, we report three cryo-electron microscopy structures of RXFP4–Gi protein complexes in the presence of the endogenous ligand insulin-like peptide 5 (INSL5) or one of the two small molecule agonists, compound 4 and DC591053. The B chain of INSL5 adopts a single α-helix that penetrates into the orthosteric pocket, while the A chain sits above the orthosteric pocket, revealing a peptide-binding mode previously unknown. Together with mutagenesis and functional analyses, the key determinants responsible for the peptidomimetic agonism and subtype selectivity were identified. Our findings not only provide insights into ligand recognition and subtype selectivity among class A G protein-coupled receptors, but also expand the knowledge of signaling mechanisms in the insulin superfamily.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.