Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

Six abomasums of yaks (Bosgrunniens) were studied with gross dissection and histological methods. It was found that the mucosa of the yak abomasum was covered with simple columnar epithelium. There were lots of spiral folds (10) in the fundic glandular area. The developed membrane of lamina propria was occupied by high density glands. According to the morphological characteristics of the glands, the abomasum was divided into the cardiac, gastric and pyloric glands. Cardiac glands were curved tubular glands with the intumescent bottom and small glandular cavity. Fundic glands were simple tubular glands or branched tubular glands, where the chief, parietal and mucous neck cells can be observed clearly. Pyloric glands were curled tubular glands, the closer to the deep of the lamina propria, the more obvious the glands curl. Staining of glycoconjugate revealed that the mucosal epithelium of the cardiac gastric and pyloric glands and gastric pits epithelium mainly secreted neutral glycoconjugate, but other portions of cardiac and gastric glands secreted mixed and acid glycoconjugate respectively. By Gordon-Sweet's reticular fiber staining, it was found that the mucous neck cells possessed the characteristic of argyrophilic phenomenon. There was a large number of argyrophilic granules in the supranuclear cytoplasm in contrast with the chief cells. Furthermore, there were isolated lymphoid nodules and diffuse lymphoid tissue in the abomasum glands, especially in corpus abomasi. Grimelius silver staining showed that the argyrophil cells were located in the glandular epithelium and lamina propria of glands, which can also be observed in connective tissue. These endocrine cells dispersed individually in epithelial cells, occasionally in 35 cell groups. Therefore, the yaks were grazed throughout the year on diverse natural grassland and had evolved morphological characteristics of the abomasum enabling them to consume a wide variety of plant species, thereby better adapting them to harsh plateau environment.

Seis abomaso yak (Bosgrunniens) fueron estudiados con disección y métodos histológicos. Se encontró que la mucosa del abomaso yak estaba cubierta de epitelio columnar simple. Se observaron pliegues en espiral (10) en la zona glandular fúndica. La membrana desarrollada de la lámina propia contenía glándulas de alta densidad. De acuerdo con las características morfológicas de las glándulas, el abomaso se dividió en las glándulas cardíacas, gástricas y pilórica. Las glándulas cardíacas se curvan en glándulas tubulares con la parte inferior intumescente y una pequeña cavidad glandular. Las glándulas fúndicas eran glándulas tubulares simples o glándulas tubulares ramificadas, donde se pueden observar con claridad las células principales, parietales y mucosas del cuello. Las glándulas pilóricas fueron glándulas tubulares curvadas, cuanto más cercanas a la lámina propia, más evidente fue su forma ondulada. La tinción glucoconjugada reveló que el epitelio de la mucosa de las glándulas gástricas cardiacas, pilóricas y el epitelio de las fosas gástricas secretaron principalmente un glucoconjugado neutro, pero otras porciones cárdicas y de las glándulas gástricas secretaron un glucoconjugado mixto y ácido, respectivamente. A la tinción de fibras reticulares, se encontró que las células mucosas del cuello poseían características argirófilas. Se observó un gran número de gránulos en el citoplasma supranuclear en contraste con las células principales. Además, no fueron aislados los nódulos linfoides y presentaba tejido linfoide difuso en las glándulas de abomaso, especialmente en el cuerpo del abomaso. La tinción Gordon Sweet indicó que las células argirofílicas se localizaron en el epitelio y lámina propia glandular, lo que también se observó en el tejido conectivo. Estas células endocrinas se dispersan individualmente en las células epiteliales, de vez en cuando en grupos celulares de 3-5. De esta forma, los yak pastorean durante todo el año, en diversos pastizales naturales, y han evolucionado sus características morfológicas que les permiten consumir una amplia variedad de especies de plantas, con lo que se adaptan mejor a las condiciones inhóspitas.

Objetivo : A visfatina é uma adipocina recentemente descoberta que contribui com as condições relacionadas à glicose e à obesidade. Até hoje, pouco se sabe da sua resposta à metformina, um agente sensibilizador de insulina, e ao exercício. Nosso objetivo foi investigar o impacto do tratamento com metformina e/ou da natação sobre a visfatina no soro e no tecido adiposo subcutâneo (TAS), tecido adiposo perirrenal (TAP) e músculo esquelético (ME) em ratos com obesidade induzida por dieta com alto teor de gordura. Materiais e métodos : Ratos Sprague-Dawley foram alimentados com uma dieta normal ou com alto teor de gordura por 16 semanas para o desenvolvimento de um modelo de obesidade. Os ratos do modelo de obesidade foram, então, randomizados para a metformina, natação ou terapia de combinação com metformina e natação, além do grupo controle de obesidade induzida por alto teor de gordura e do grupo controle normal. Cada grupo apresentava 10 ratos. Parâmetros zoométricos e glicêmicos, perfil lipídico e níveis de visfatina sérica foram avaliados no momento inicial e após seis semanas de tratamento. Os níveis de visfatina em TAS, TAP e ME foram determinados por Western Blot. Resultados : A metformina e a natação melhoraram o perfil lipídico e aumentaram a sensibilidade à insulina, com redução do peso corporal. Tanto a metformina quanto a natação levaram à regulação para baixo dos níveis de visfatina no TAS e TAP, enquanto a terapia de combinação apresentou os maiores benefícios, mas não foram observadas alterações nos níveis de visfatina no ME. Conclusão : Nossos resultados indicam que a regulação para baixo da visfatina no TAS e TAP pode ser um dos mecanismos pelos quais a metformina e a natação inibem a obesidade.

Objective : Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Materials and methods : Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Results : Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Conclusion : Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.

Considering the effects of the changes of the pore water pressure around the opening, the construction sequence of the tunnel and the interaction between the liner and the surrounding geomaterial on the mechanical response of the tunnel and in conjunction with the analyses of the continuity and boundary conditions for the stress and displacement and hydraulic conditions, the elastic problem for a deep pressure tunnel with impermeable liner in a saturated elastic porous media that obeys Terzaghi's effective stress principle is investigated. The influences of the relative liner thickness and rigidity and the relative distance of the point under investigation to the tunnel axis on the stress-displacement fields for various combinations of the mechanical and geometric parameters are evaluated and discussed.