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The substantial merit of Cordyceps s.l. spp. in terms of medicinal benefits is largely appreciated. Nevertheless, only few studies have characterized and examined the clinical complications of the use of health tonics containing these species. Here, we epitypified C. formosana isolates that were collected and characterized as Ophiocordyceps formosana based on morphological characteristics, molecular phylogenetic analyses, and metabolite profiling. Thus, we renamed and transferred C. formosana to the new protologue Ophiocordyceps formosana (Kobayasi & Shimizu) Wang, Tsai, Tzean & Shen comb. nov. Additionally, the pharmacological potential of O. formosana was evaluated based on the hot-water extract from its mycelium. The relative amounts of the known bioactive ingredients that are unique to Cordyceps s.l. species in O. formosana were found to be similar to the amounts in O. sinensis and C. militaris, indicating the potential applicability of O. formosana for pharmacological uses. Additionally, we found that O. formosana exhibited antioxidation activities in vitro and in vivo that were similar to those of O. sinensis and C. militaris. Furthermore, O. formosana also displayed conspicuously effective antitumor activity compared with the tested Cordyceps s.l. species. Intrinsically, O. formosana exhibited less toxicity than the other Cordyceps species. Together, our data suggest that the metabolites of O. formosana may play active roles in complementary medicine. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Focal adhesion kinase is implicated in the regulation of cell adhesion, migration, survival, and cell-cycle progression. However, the functions of focal adhesion kinase in endothelial cell (EC) in vivo remain unclear. This study aims to examine the role of FAK in EC function and angiogenesis in vivo by transgenic mice approach. Method: We generated transgenic mice which overexpressed chicken FAK in vascular endothelial cell under the control of the Tie-2 promoter and enhancer. FAK transgene was detected by RT-PCR, immunoprecipitation, and Western blot. The effect of FAK overexpression on angiogenesis was determined using skin wound healing and ischemia skeleton muscle models. Results: Expression of FAK transgene was detected in all vessel-rich tissues. Expression of FAK protein was verified by antibody specific for the exogenous chicken FAK in lung homogenates and isolated EC. In the wound-induced angiogenesis model, the number of vessels in the granulation tissue of healing wound was significantly increased in the transgenic mouse compared to that of wild-type control mice. Similarly, in the ischemia skeleton muscle model, the density of capillaries was significantly increased in the transgenic mouse. Conclusion: These results indicate that FAK may play an important role in the promotion of angiogenesis in vivo. [Copyright &y& Elsevier]

Camellia sinensis (L.) O. Kuntze, commonly known as tea, is widely cultivated around the world in tropical and subtropical areas. Tea is mainly manufactured using young shoots of tea plants. Therefore, it is essential to control foliar diseases. Gray blight disease is caused by pestalotiopsis-like taxa and is known as one of the most destructive tea diseases. Although several studies have provided the groundwork for the fungal diseases associated with C. sinensis in Taiwan, gray blight disease has not been characterized based on diversity, molecular systematics, or pathogenicity. The goal of this study was to identify and characterize the causative agents of tea gray blight disease. A total of 98 pestalotiopsis-like isolates associated with symptomatic leaves of C. sinensis from major tea fields in Taiwan were investigated. Based on phylogenies of single and concatenated DNA sequences (internal transcribed spacer, β-tubulin, translation elongation factor 1-α) together with morphology, we resolved most of the pestalotiopsis-like species in this study. The study revealed seven well-classified taxa and seven tentative clades in three genera: Pestalotiopsis , Pseudopestalotiopsis , and Neopestalotiopsis . One novel species, Pseudopestalotiopsis annellata , was introduced. Five new records, Pseudopestalotiopsis chinensis , Pseudopestalotiopsis camelliae-sinensis , Pestalotiopsis camelliae , Pestalotiopsis yanglingensis , and Pestalotiopsis trachicarpicola , were introduced for the first time in Taiwan. Pseudopestalotiopsis chinensis was the taxon most frequently isolated from C. sinensis in this study. Furthermore, results of pathogenicity assessments exhibited that, with wound inoculation, all assayed isolates in this study were pathogenic on tea leaves. Pseudopestalotiopsis chinensis and Pseudopestalotiopsis camelliae-sinensis were identified as the major pathogens associated with gray blight disease of tea in Taiwan. To our knowledge, this is the first study of the diversity, pathogenicity, and characterization of pestalotiopsis-like fungi causing tea gray blight disease in Taiwan.

Lysophosphatidic acid (LPA) is a bioactive lipid growth factor which is present in high levels in serum and platelets. LPA binds to its specific G-protein-coupled receptors, including LPA 1 to LPA 6 , thereby regulating various physiological functions, including cancer growth, angiogenesis, and lymphangiogenesis. Our previous study showed that LPA promotes the expression of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C in prostate cancer (PCa) cells. Interestingly, LPA has been shown to regulate the expression of calreticulin (CRT), a multifunctional chaperone protein, but the roles of CRT in PCa progression remain unclear. Here we investigated the involvement of CRT in LPA-mediated VEGF-C expression and lymphangiogenesis in PCa. Knockdown of CRT significantly reduced LPA-induced VEGF-C expression in PC-3 cells. Moreover, LPA promoted CRT expression through LPA receptors LPA 1 and LPA 3 , reactive oxygen species (ROS) production, and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α). Tumor-xenografted mouse experiments further showed that CRT knockdown suppressed tumor growth and lymphangiogenesis. Notably, clinical evidence indicated that the LPA-producing enzyme autotaxin (ATX) is related to CRT and that CRT level is highly associated with lymphatic vessel density and VEGF-C expression. Interestingly, the pharmacological antagonist of LPA receptors significantly reduced the lymphatic vessel density in tumor and lymph node metastasis in tumor-bearing nude mice. Together, our results demonstrated that CRT is critical in PCa progression through the mediation of LPA-induced VEGF-C expression, implying that targeting the LPA signaling axis is a potential therapeutic strategy for PCa., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Loss of lung-fluid homeostasis is the hallmark of acute lung injury (ALI). Association of catenins and actin cytoskeleton with vascular endothelial (VE)-cadherin is generally considered the main mechanism for stabilizing adherens junctions (AJs), thereby preventing disruption of lung vascular barrier function. The present study identifies endothelial focal adhesion kinase (FAK), a nonreceptor tyrosine kinase that canonically regulates focal adhesion turnover, as a novel AJ-stabilizing mechanism. In wild-type mice, induction of ALI by intraperitoneal administration of lipopolysaccharide or cecal ligation and puncture markedly decreased FAK expression in lungs. Using a mouse model in which FAK was conditionally deleted only in endothelial cells (ECs), we show that loss of EC-FAK mimicked key features of ALI (diffuse lung hemorrhage, increased transvascular albumin influx, edema, and neutrophil accumulation in the lung). EC-FAK deletion disrupted AJs due to impairment of the fine balance between the activities of RhoA and Rac1 GTPases. Deletion of EC-FAK facilitated RhoA's interaction with p115-RhoA guanine exchange factor, leading to activation of RhoA. Activated RhoA antagonized Rac1 activity, destabilizing AJs. Inhibition of Rho kinase, a downstream effector of RhoA, reinstated normal endothelial barrier function in FAK-/- ECs and lung vascular integrity in EC-FAK-/- mice. Our findings demonstrate that EC-FAK plays an essential role in maintaining AJs and thereby lung vascular barrier function by establishing the normal balance between RhoA and Rac1 activities.

Manipulating an incorporated scaffold to direct cell behaviors play a key role in tissue engineering. In this study, we developed novel nano-topographic oxidized silicon nanosponges capable of being modified with various chemicals of a few nm in thickness to gain further insight into the fundamental biology of cell-environment interactions in vitro. A wet etching technique was applied to fabricate the silicon nanosponges in a high-throughput manner and was followed by vapor deposition of various organo-silane chemicals to enable self-assembly on the surfaces of the silicon nanosponges. When Chinese hamster ovary cells were cultured on these chemically modified nano-topographic structures, they displayed distinct morphogenesis, adherent responses, and biochemical properties in comparison with those of their planar oxidized silicon counterparts. There were predominant nano-actin punches and slender protrusions formed while cells were cultured on the nano-topographic structures, indicating that cell behaviors can be influenced by the physical characteristic derived from nano-topography, in addition to the hydrophobicity of contact surfaces. This study demonstrates potential applications of these nano-topographic biomaterials for controlling cell development in tissue engineering as well as in basic cell biology research.

The enzyme beta1,4-N-acetylgalactosaminyltransferase III (beta4GalNAc-T3) exhibits in vitro activity of synthesizing N,N'-diacetyllactosediamine, GalNAcbeta1,4GlcNAc. Here, we investigate the expression of beta4GalNAc-T3 in primary colon tumors and the effects of its overexpression on HCT116 colon cancer cells. Real-time reverse transcription-PCR showed that the expression of beta4GalNAc-T3 was up-regulated in 72.5% (n = 40) of primary colon tumors compared with their normal counterparts. beta4GalNAc-T3 overexpression resulted in enhanced cell-extracellular matrix adhesion, migration, anchorage-independent cell growth, and invasion of colon cancer cells. Moreover, beta4GalNAc-T3 overexpression increased tumor growth and metastasis and decreased survival of tumor-bearing nude mice. beta4GalNAc-T3 overexpression showed increased tyrosine phosphorylation of focal adhesion kinase and paxillin Y118 as well as increased extracellular signal-regulated kinase phosphorylation. These results suggest that up-regulation of beta4GalNAc-T3 may play a critical role in promoting tumor malignancy and that integrin and mitogen-activated protein kinase signaling pathways could be involved in the underlying mechanism.