Author: Lin, Chang-Ni ; Wu, Yi-Ying ; Hsu, Keng-Fu ; Lin, Chun-Hong ; Kang, Chieh-Yi ; Hsu, Ching-Cheng ; Hsu, Pang-Hung ; Tsai, Yi-Cheng ; Lee, Gwo-Bin ; Liang, Yu-Ling

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy owing to its high chemoresistance and late diagnosis, which lead to a poor prognosis. Hence, developing new therapeutic modalities is important for OvCa patient treatment. Our previous results indicated that a novel aptamer, Tx-01, can specifically recognize serous carcinoma cells and tissues. Here, we aim to clarify the clinical role and possible molecular mechanisms of Tx-01 in OvCa. Immunostaining and statistical analysis were performed to detect the interaction of Tx-01 and heat shock protein 70/Notch1 intracellular domain (HSP70/NICD) in OvCa. The in vitro and in vivo experiments were carried out to demonstrate the potential mechanisms of Tx-01. Results show that Tx-01 reduced serous OvCa OVCAR3 cell migration and invasion and inhibited HSP70 nuclear translocation by interrupting the intracellular HSP70/NICD interaction. Furthermore, Tx-01 suppressed serous-type OVCAR3 cell tumor growth in vivo. Tx-01 acts as a prognostic factor through its interaction with membrane-bound HSP70 (mHSP70 that locates on the cell surface without direct interaction to NICD) on ascitic circulating tumor cells (CTCs) and is reported to be involved in natural killer (NK) cell recognition and activation. Our data demonstrated that Tx-01 interacted with HSP70 and showed therapeutic and prognostic effects in serous OvCa. Tx-01 might be a potential inhibitor for use in serous OvCa treatment.

01 Dec 2019·Veterinary ResearchQ2 · AGRICULTURAL & FORESTRY SCIENCE

HutZ is required for biofilm formation and contributes to the pathogenicity of Edwardsiella piscicida

Q2 · AGRICULTURAL & FORESTRY SCIENCE

ArticleOA

Author: Fang, Qing-Jian ; Shi, Yan-Jie ; Hu, Yong-Hua ; Gong, Chun-Guang ; Huang, Hui-Qin

AbstractEdwardsiella piscicidais a severe fish pathogen. Haem utilization systems play an important role in bacterial adversity adaptation and pathogenicity. In this study, a speculative haem utilization protein, HutZEp, was characterized inE. piscicida.hutZEpis encoded with two other genes,hutWandhutX, in an operon that is similar to the haem utilization operonhutWXZidentified inV. cholerae. However, protein activity analysis showed that HutZEpis probably not related to hemin utilization. To explore the biological role of HutZEp, a markerlesshutZEpin-frame mutant strain, TX01ΔhutZ, was constructed. Deletion ofhutZEpdid not significantly affect bacterial growth in normal medium, in iron-deficient conditions, or in the presence of haem but significantly retarded bacterial biofilm growth. The expression of known genes related to biofilm growth was not affected byhutZEpdeletion, which indicated that HutZEpwas probably a novel factor promoting biofilm formation inE. piscicida. Compared to the wild-type TX01, TX01ΔhutZexhibited markedly compromised tolerance to acid stress and host serum stress. Pathogenicity analysis showed that inactivation ofhutZEpsignificantly impaired the ability ofE. piscicidato invade and reproduce in host cells and to infect host tissue. In contrast to TX01, TX01ΔhutZwas defective in blocking host macrophage activation. The expression ofhutZEpwas directly regulated by the ferric uptake regulator Fur. This study is the first functional characterization of HutZ in a fish pathogen, and these findings suggested that HutZEpis essential forE. piscicidabiofilm formation and contributes to host infection.

01 Dec 2019·Fish & Shellfish ImmunologyQ2 · AGRICULTURAL & FORESTRY SCIENCE

Universal stress proteins contribute Edwardsiella piscicida adversity resistance and pathogenicity and promote blocking host immune response

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Han, Yue-Xin ; Fang, Qing-Jian ; Fang, Zai-Guang ; Huang, Hui-Qin ; Hu, Yong-Hua ; Shi, Yan-Jie

Universal stress proteins (Usps) exist ubiquitously in bacteria and other organisms. Usps play an important role in adaptation of bacteria to a variety of environmental stresses. There is increasing evidence that Usps facilitate pathogens to adapt host environment and are involved in pathogenicity. Edwardsiella piscicida (formerly included in E. tarda) is a severe fish pathogen and infects various important economic fish including tilapia (Oreochromis niloticus). In E. piscicida, a number of systems and factors that are involved in stress resistance and pathogenesis were identified. However, the function of Usps in E. piscicida is totally unknown. In this study, we examined the expressions of 13 usp genes in E. piscicida and found that most of these usp genes were up-regulated expression under high temperature, oxidative stress, acid stress, and host serum stress. Particularly, among these usp genes, usp13, exhibited dramatically high expression level upon several stress conditions. To investigate the biological role of usp13, a markerless usp13 in-frame mutant strain, TX01Δusp13, was constructed. Compared to the wild type TX01, TX01Δusp13 exhibited markedly compromised tolerance to high temperature, hydrogen peroxide, and low pH. Deletion of usp13 significantly retarded bacterial biofilm growth and decreased resistance against serum killing. Pathogenicity analysis showed that the inactivation of usp13 significantly impaired the ability of E. piscicida to invade into host cell and infect host tissue. Introduction of a trans-expressed usp13 gene restored the lost virulence of TX01Δusp13. In support of these results, host immune response induced by TX01 and TX01Δusp13 was examined, and the results showed reactive oxygen species (ROS) levels in TX01Δusp13-infected macrophages were significantly higher than those in TX01-infected cells. The expression level of several cytokines (IL-6, IL-8, IL-10, TNF-α, and CC2) in TX01Δusp13-infected fish was significantly higher than that in TX01-infected fish. These results suggested that the deletion of usp13 attenuated the ability of bacteria to overcome the host immune response to pathogen infection. Taken together, our study indicated Usp13 of E. piscicida was not only important participant in adversity resistance, but also was essential for E. piscicida pathogenicity and contributed to block host immune response to pathogen infection.

100 Deals associated with Filgrastim-txid

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Indication	Country/Location	Organization	Date
Acute Myeloid Leukemia	US	Tanvex BioPharma USA, Inc.	28 Jun 2024
Bone marrow depression	US	Tanvex BioPharma USA, Inc.	28 Jun 2024
Neutropenia	CA	Tanvex BioPharma USA, Inc.	01 Oct 2021

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