The potential of epigallocatechin gallate in the chemoprevention and therapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), one of the most notorious malignancies globally, has a high fatality and poor prognosis. Though remarkable breakthroughs have been made in the therapeutic strategies recently, the overall survival of HCC remains unsatisfactory. Consequently, the therapy of HCC remains a great challenge. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from the leaves of the tea bush, has been extensively investigated for its antitumor effects. In this review, we summarize the previous literature to elucidate the roles of EGCG in the chemoprophylaxis and therapy of HCC. Accumulating evidence has confirmed EGCG prevents and inhibits the hepatic tumorigenesis and progression through multiple biological mechanisms, mainly involving hepatitis virus infection, oxidative stress, proliferation, invasion, migration, angiogenesis, apoptosis, autophagy, and tumor metabolism. Furthermore, EGCG enhances the efficacy and sensitivity of chemotherapy, radiotherapy, and targeted therapy in HCC. In conclusion, preclinical studies have confirmed the potential of EGCG for chemoprevention and therapy of HCC under multifarious experimental models and conditions. Nevertheless, there is an urgent need to explore the safety and efficacy of EGCG in the clinical practice of HCC

A Facile Synthesis of ZnCo\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e4\u3c/sub\u3e Nanocluster Particles and the Performance as Anode Materials for Lithium Ion Batteries

ZnCo2O4 nanocluster particles (NCPs) were prepared through a designed hydrothermal method, with the assistance of a surfactant, sodium dodecyl benzene sulfonate. The crystalline structure and surface morphology of ZnCo2O4 were investigated by XRD, XPS, SEM, TEM, and BET analyses. The results of SEM and TEM suggest a clear nanocluster particle structure of cubic ZnCo2O4 (~100 nm in diameter), which consists of aggregated primary nanoparticles (~10 nm in diameter), is achieved. The electrochemical behavior of synthesized ZnCo2O4 NCPs was investigated by galvanostatic discharge/charge measurements and cyclic voltammetry. The ZnCo2O4 NCPs exhibit a high reversible capacity of 700 mAh g−1 over 100 cycles under a current density of 100 mA g−1 with an excellent coulombic efficiency of 98.9% and a considerable cycling stability. This work demonstrates a facile technique designed to synthesize ZnCo2O4 NCPs which show great potential as anode materials for lithium ion batteries

Signalling pathways regulating galactosaminoglycan synthesis and structure in vascular smooth muscle: implications for lipoprotein binding and atherosclerosis

Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in blood vessels by modified proteoglycans (PGs) with hyperelongated glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated hyperelongation regulates the composition and size of PGs in a manner that would cause low density lipoprotein (LDLs) retention in vessel wall. Galactosaminoglycans are a class of GAGs, commonly observed on PGs. Multiple enzymes are involved in galactosaminoglycan biosynthesis. Galactosaminoglycan synthesis is regulated by various signalling pathways which are amenable to pharmacological manipulation to treat atherosclerosis. Receptor mediated signalling pathways including protein tyrosine kinase receptors (PTKRs), serine/threonine kinase receptors (S/TKRs) and G-protein coupled receptors (GPCRs) pathways regulate galactosaminoglycan synthesizing enzyme expression. Increased expression of these enzymes modify galactosaminoglycan chain structure by making them hyperelongated. This review focuses on the signalling pathways regulating the expression of genes involved in galactosaminoglycan synthesis and modification. Furthemore, there are multiple other processes for inhibiting the interactions between LDL and galactosaminoglycans such as peptide mimetics of ApoB100 and anti-galactosaminoglycan antibodies and the therapeutic potential of these strategies is also addressed

Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine.

SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8-90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals. We performed in-depth medical examinations and exome sequencing in the homozygous individuals. All homozygous individuals had persistent hypercholanemia (P = 5.8 × 10-29). Exome sequencing excluded the involvement of other BA metabolism-associated genes in the hypercholanemia. Although asymptomatic, all individuals had low vitamin D levels. Of six adults that were subjected to bone mineral density analysis, three presented with osteoporosis/osteopenia. Sex hormones and blood lipids were deviated in all subjects. Homozygosity of p.Ser267Phe in SLC10A1 is associated with asymptomatic hypercholanemia. Individuals with homozygous p.Ser267Phe in SLC10A1 are prone to vitamin D deficiency, deviated sex hormones and blood lipids. Surveillance of these parameters may also be needed in patients treated with drugs targeting NTCP.This project is supported by the National Natural Science Foundation of China (31471193, 81570539, 81370535, 91331204 and 31525014). S.X. acknowledges financial support from the Strategic Priority Research Program (XDB13040100) and Key Research Program of Frontier Sciences (QYZDJ-SSW-SYS009) of the Chinese Academy of Sciences (CAS)

A Highly Dense Genetic Map for Ginkgo biloba Constructed Using Sequence-Based Markers

Ginkgo biloba L. is a well-known living gymnosperm fossil that has medicinal and ornamental value. In this study, a high density genetic map was constructed with megagametophytes of 94 seeds from a single Ginkgo tree by employing the specific-locus amplified fragment (SLAF) sequencing technique. The average sequencing depth was 11.20×, which yielded 538,031 high-quality SLAFs. Among these SLAFs, 204,361 were heterozygous in the maternal tree and segregated in the progeny. The established map contained 12,263 SLAFs that were assigned to 12 linkage groups (LGs). The number of LGs on this map equaled the number of chromosomes in Ginkgo. The total map length was 1,671.77 cM, with an average distance of 0.89 cM between adjacent marker bins. Map evaluation based on the haplotype map and the heat map validated the high quality of the established map. Because Ginkgo is an economically and biologically important tree, strenuous efforts have been exerted to sequence its genome. This new map, built using sequence-based markers, will serve in the future as a fundamental platform for anchoring sequence assemblies along Ginkgo chromosomes. This map also provides a desirable platform for various genetic studies of Ginkgo, including gene/quantitative trait locus mapping and marker-aided selection

Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma production and bioinformatics prediction

<p>Abstract</p> <p>Background</p> <p>Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epitopes. Analysis of the functional importance of side-chains by mutational study may exaggerate the effect by imposing a structural disturbance or an unusual steric, electrostatic or hydrophobic interaction.</p> <p>Results</p> <p>We demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover, S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN, SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine (A), lysine (K) or aspartic acid (D), respectively. ANN was used to estimate the binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were predicated to possess the most important role in peptide binding. Additionally, these one residue mutated peptides were synthesized, and IFN-gamma production induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased obviously.</p> <p>Conclusions</p> <p>We demonstrated that S366-374 is an optimal H-2 Kd CTL epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact with TCR on the surface of CD8-T cells.</p

Microstrip Antenna with High Gain and Strong Directivity Loaded with Cascaded Hexagonal Ring-Shaped Metamaterial

A new cascaded hexagonal ring-shaped metamaterial element is designed, which is arranged periodically and placed on the top of a traditional microstrip antenna to optimize the performance of the traditional antenna. The simulation results show that the new metamaterial microstrip antenna works at near 10 GHz, the impedance bandwidth is extended by 0.25 GHz and the gain is increased by 113.6% compared with a traditional microstrip antenna. Cross-shaped slots are etched on the ground plate of the microstrip antenna to widen the impedance bandwidth. It is shown that the impedance bandwidths at the resonant frequencies of 10 GHz and 14 GHz are broadened by 0.06 GHz and 0.56 GHz, respectively, and the gain of the slot-etched antenna is 13.454 dB. After the metamaterial unit structure is optimized, a nested double-hexagon ring-shaped electromagnetic metamaterial unit structure is proposed. The metamaterial slot microstrip antenna operates in two frequency bands of 10 GHz and 14 GHz; the relative bandwidths are increased to 16.9% and 19.4% with two working bandwidths of 1.74 GHz and 4.98 GHz, respectively; and the gain and directivity are also improved compared with the traditional microstrip antenna. The metamaterial unit structure proposed in this paper is of certain reference value for the variety of metamaterial and the application of metamaterial in traditional microstrip antennas