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81.
Byeong Tak Jeon Rok Won Heo Hyun Joo Shin Chin-ok Yi Yu Hee Lee Han-nah Joung 《Bioscience, biotechnology, and biochemistry》2013,77(3):482-489
A Vigna nakashimae (VN) extract has been shown to have antidiabetic and anti-obesity effects. However, the mechanism underlying the effect of a VN extract on hepatic inflammation and endoplasmic reticulum (ER) stress remains unclear. In the present study, we investigated how a VN extract protects against the development of non-alcoholic fatty liver disease (NAFLD). A VN extract for 12 weeks reduced the body weight, serum metabolic parameters, cytokines, and hepatic steatosis in high-fat diet (HFD)-fed mice. A VN extract decreased HFD-induced hepatic acetyl CoA carboxylase and glucose transporter 4 expressions. In addition to the levels of high-mobility group box 1 and receptor for advanced glycation, the hepatic expression of ATF4 and caspase-3 was also reduced by a VN extract. Thus, these data indicate that a chronic VN extract prevented NAFLD through multiple mechanisms, including inflammation, ER stress, and apoptosis in the liver. 相似文献
82.
83.
Two silicone coatings have been evaluated for barnacle adhesion. One coating is an unfilled hydrosilation cured polydimethylsiloxane (PDMS) network, while the other is a room temperature vulcanized (RTV), filled, ethoxysiloxane cured PDMS elastomer, RTV11?. The adhesion strength of one species of barnacle, Balanus eburneus, to the hydrosilation coatings is in the range of 0.37–0.60 kg cm‐2 while the corresponding range for RTV11 is 0.64–0.90 kg cm‐2. The easier release of B. eburneus from the hydrosilation cured network compared to RTV11 is discussed in relationship to differences in bulk and surface properties. Preliminary results suggest bulk modulus may be the most important parameter in determining barnacle adhesion strength. In light or mechanical property analysis, a re‐evaluation of surface properties and chemical stability is presented. 相似文献
84.
Rong Jiang Bozena Frackowiak Youseung Shin Xinyi Song Weimin Chen Li Lin Michael D. Cameron Derek R. Duckett Theodore M. Kamenecka 《Bioorganic & medicinal chemistry letters》2013,23(9):2683-2687
Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure. 相似文献
85.
Non hemolytic short peptidomimetics as a new class of potent and broad-spectrum antimicrobial agents
Ravichandran N. Murugan Binu Jacob Eun-Hee Kim Mija Ahn Hoik Sohn Ji-Hyung Seo Chaejoon Cheong Jae-Kyung Hyun Kyung S. Lee Song Yub Shin Jeong Kyu Bang 《Bioorganic & medicinal chemistry letters》2013,23(16):4633-4636
Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics. 相似文献
86.
A set of grid type knowledge‐based energy functions is introduced for ?–χ1, ψ–χ1, ?–ψ, and χ1–χ2 torsion angle combinations. Boltzmann distribution is assumed for the torsion angle populations from protein X‐ray structures, and the functions are named as statistical torsion angle potential energy functions. The grid points around periodic boundaries are duplicated to force periodicity, and the remedy relieves the derivative discontinuity problem. The devised functions rapidly improve the quality of model structures. The potential bias in the functions and the usefulness of additional secondary structure information are also investigated. The proposed guiding functions are expected to facilitate protein structure modeling, such as protein structure prediction, protein design, and structure refinement. Proteins 2013. Proteins 2013; 81:1156–1165. © 2013 Wiley Periodicals, Inc. 相似文献
87.
Ping Sun John C. Clamp Dapeng Xu Bangqin Huang Mann Kyoon Shin Franziska Turner 《Proceedings. Biological sciences / The Royal Society》2013,280(1771)
Vorticella includes more than 100 currently recognized species and represents one of the most taxonomically challenging genera of ciliates. Molecular phylogenetic analysis of Vorticella has been performed so far with only sequences coding for small subunit ribosomal RNA (SSU rRNA); only a few of its species have been investigated using other genetic markers owing to a lack of similar sequences for comparison. Consequently, phylogenetic relationships within the genus remain unclear, and molecular discrimination between morphospecies is often difficult because most regions of the SSU rRNA gene are too highly conserved to be helpful. In this paper, we move molecular systematics for this group of ciliates to the infrageneric level by sequencing additional molecular markers—fast-evolving internal transcribed spacer (ITS) regions—in a broad sample of 66 individual samples of 28 morphospecies of Vorticella collected from Asia, North America and Europe. Our phylogenies all featured two strongly supported, highly divergent, paraphyletic clades (I, II) comprising the morphologically defined genus Vorticella. Three major lineages made up clade I, with a relatively well-resolved branching order in each one. The marked divergence of clade II from clade I confirms that the former should be recognized as a separate taxonomic unit as indicated by SSU rRNA phylogenies. We made the first attempt to elucidate relationships between species in clade II using both morphological and multi-gene approaches, and our data supported a close relationship between some morphospecies of Vorticella and Opisthonecta, indicating that relationships between species in the clade are far more complex than would be expected from their morphology. Different patterns of helix III of ITS2 secondary structure were clearly specific to clades and subclades of Vorticella and, therefore, may prove useful for resolving phylogenetic relationships in other groups of ciliates. 相似文献
88.
Tae-Hwan Ha HyungChul Ryu Sung-Eun Kim Ho Shin Kim Jihyae Ann Phuong-Thao Tran Van-Hai Hoang Karam Son Minghua Cui Sun Choi Peter M. Blumberg Robert Frank Gregor Bahrenberg Klaus Schiene Thomas Christoph Sven Frormann Jeewoo Lee 《Bioorganic & medicinal chemistry》2013,21(21):6657-6664
A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode. 相似文献
89.
Masaki Setoguchi Shin Iimura Yuuichi Sugimoto Yoshiyuki Yoneda Jun Chiba Toshiyuki Watanabe Fumihito Muro Yutaka Iigo Gensuke Takayama Mika Yokoyama Tomoe Taira Misato Aonuma Tohru Takashi Atsushi Nakayama Nobuo Machinaga 《Bioorganic & medicinal chemistry》2013,21(1):42-61
We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys. 相似文献
90.
Shin Hamada Kennichi Satoh Shin Miura Morihisa Hirota Atsushi Kanno Atsushi Masamune Kazuhiro Kikuta Kiyoshi Kume Jun Unno Shinichi Egawa Fuyuhiko Motoi Michiaki Unno Tooru Shimosegawa 《Journal of cellular physiology》2013,228(6):1255-1263
Invasive ductal adenocarcinoma (IDA) of the pancreas manifests poor prognosis due to the early invasion and distant metastasis. In contrast, intraductal papillary mucinous adenoma or carcinoma (IPMA or IPMC) reveals better clinical outcomes. Various molecular mechanisms contribute to these differences but entire picture is still unclear. Recent researches emphasized the important role of miRNA in biological processes including cancer invasion and metastasis. We previously described that miR‐126 is down‐regulated in IDA compared with IPMA or IPMC, and miR‐126 regulates the expression of invasion related molecule disintegrin and metalloproteinase domain‐containing protein 9 (ADAM9). Assessing the difference of miRNA expression profiles of IDA, IPMA, and IPMC, we newly identified miR‐197 as an up‐regulated miRNA specifically in IDA. Expression of miR‐197 in pancreatic cancer cells resulted in the induction of epithelial–mesenchymal transition (EMT) along with the down‐regulation of p120 catenin which is a putative target of miR‐197. Direct interaction between miR‐197 and p120 catenin mRNA sequence was confirmed by 3′UTR assay, and knockdown of p120 catenin recapitulated EMT induction in pancreatic cancer cells. In situ hybridization of miR‐197 and immunohistochemistry of p120 catenin showed mutually exclusive patterns suggesting pivotal role of miR‐197 in the regulation of p120 catenin. This miR‐197/p120 catenin axis could be a novel therapeutic target. J. Cell. Physiol. 228: 1255–1263, 2013. © 2012 Wiley Periodicals, Inc. 相似文献