Introduction: Recently, MicroRNAs have gained increasing popularity as a novel nucleic acid-mediated medicine to regulate cancer-related protein expression. MicroRNA-21 (miR-21) is known as an oncogenic microRNA which is overexpressed in almost all cancers, including ovarian carcinoma that causes cisplatin (cis-Pt) resistance and vascular endothelial growth factor (VEGF) upregulation. So, miRNA-based therapy can be regarded as knocking down miR-21 expression, inducing tumor cell apoptosis, and suppressing tumor-associated angiogenesis. Methods: PEG5k-carboxymethylated polyethyleneimine nanohydrogels (PEG5k-CMPEI) were loaded with AntagomiR-21 (As-21) at different ratios of nitrogen to phosphorus (N/P). Particle size and ζ potential were determined for the As-21 loaded nanohydrogels. In the cellular experiments, miR-21 expression, cytotoxicity, and cis-Pt sensitivity were studied on A2780 ovarian cancer cell lines. Finally, tumor cell apoptosis and tumor cell-associated angiogenesis were explored in vitro and in vivo. Results: The nanohydrogels, featuring homogeneous size distribution and redox-responsiveness, were steadily loaded by As-21 at the optimum N/P ratio of 5 without any aggregation as determined by transmission electron microscopy (TEM). As-21-loaded nanohydrogels caused sequence-specific suppression of miR-21 expression and provoked apoptosis through ROS generation and caspase 3 activation. Cisplatin cytotoxicity was remarkably enhanced in A2780R as compared to A2780S following co-incubation with As-21-loaded nanohydrogels. Interestingly, the condition of the medium derived from As-21 nanohydrogel-treated A2780R cells inhibited VEGF suppression in human umbilical vein endothelial cells (HUVECs) and the formation of tubes in Matrigel. Moreover, the condition medium caused angiogenesis inhibition in the chicken chorioallantoic membrane (CAM) model. Conclusion: These results suggest that nanohydrogel-based delivery of As-21 can be a promising neoadjuvant therapy for treating resistant tumors via apoptosis induction and angiogenesis suppression.
The aim of present study was to identify the clinical signs, gross and histopathological findings in turkeys experimentally infected with highly pathogenic avian influenza virus A/duck/Vietnam/12/2005 (H5N1). Specific pathogens free of white turkeys having 6 weeks old were inoculated with 0.1 mL of the virus with 10 EID. Death was event at 3 DPI. Gross lesions observed after necropsy were splenomegaly, 5 50 pulmonary edema, severe congestion in lungs, hyperemia in brain as well as cecal-tonsil and congestion in skeletal muscle. Histopathological finding were multi organ necrosis and/or inflammation. The most consistent and severely affected organs were spleen, lungs, brain, pancreas and cecal-tonsil. It would be worth to mention that the lungs and spleen were most affected organs, among the others grossly and histopathologically, However to our knowledge, this is the first description of histopathological finding of highly pathogenic avian influenza virus A/Duck/Vietnam/12/2005 (H5N1) in turkey.
Influenza viruses can induce cell death in their host through apoptosis or necrosis.The H9N2 is a subtype of the Avian Influenza Virus (AIV) that can cause severe damage to reproductive organs of laying hens. The present study aimed to investigate the effect of the H9N2 influenza virus on apoptosis of testicular cells in chicken embryos. To this end, A/Chicken/Tehran/ZMT-101/99(H9N2) was inoculated to 210 embryonated fifteen-day-old eggs laid by SPF hens. Then, according to the experiment design, live embryos were dissected on the 19th and 21st days of fetal life and on the 25th day after birth for pathological and molecular studies and evaluation of gene expression in testicular tissue. Dissected tissues were stained with hematoxylin and eosin (HE) and studied under an optical microscope at 400x magnification. For molecular studies, viral RNA was extracted from testicular tissues, replicated by RT-PCR, and finally evaluated H9N2. Then, the genes expression involved in the testicular tissue cells apoptosis was evaluated through real-time PCR. Pathological studies indicated that H9N2 caused lesions in testicular tissue orchitis, seminiferous, and nephritis of the host. Molecular studies also showed that H9N2 replication in the host body increases BAX and Caspase 3 expression and reduces the expression of Bcl-2 and Bcl-XL. These changes in gene expression increased apoptosis and induced cell death in the host. In summary, the study findings suggested that H9N2 can increase the expression of pro-apoptotic genes and reduce the expression of anti-apoptotic genes, resulting in severe destruction of testicular tissue caused by cell apoptosis.
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