New Potential MicroRNA Biomarkers in Human Immunodeficiency Virus Elite Controllers, Human Immunodeficiency Virus Infections, and Coinfections with Hepatitis B Virus or Hepatitis C Virus.

INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.

Human papillomavirus maybe is a critical player in the regulation of chemoresistance related factors (P53, Rb, TWIST, Bcl-2, Bcl-XL, c-IAP2, cytochrome C, and caspase 3) in breast cancer.

As one of the frequent malignancies, breast cancer (BCa) is the foremost reason for cancer-related deaths among women. The role of Human papillomavirus (HPV) in chemoresistance has rarely been investigated in previous studies. The current study sets out to the possible role of HPV in BCa chemoresistance. In this research, 90 BCa tissue and 33 normal breast tissue were collected. We evaluated the presence of the HPV genome along with the viral (E2, E6, E7) and cellular gene expression associated with cell resistance to death. Statically significant differences in the prevalence of HPV between the BCa group (25.2% or 23/90) and the control group (21.8% or 7/32) were not found. HPV-16 and HPV-18 genotypes were the abundant HPV genotypes. Resistance to the Adriamycin-Cyclophosphamide (AC), paclitaxel regimen was elevated in the HPV- group (56/70) in comparison to the HPV+ group (14/70). Nevertheless, there was no significant difference in the prevalence of resistance to AC + paclitaxel + triple-negative breast cancer combination therapy between the HPV+ group (9/20) and in the HPV- group (11/20). In the BCa group in contrast to the control group, the expression level of Bcl-2, BCL-XL, and c-IAP2 demonstrated a significant decrease, while, the expression level of cytochrome C and caspase 3 was significantly increased. This study suggests that HPV infection might contribute to BCa chemoresistance through disrupt cellular genes involved in cell death.

The role of HPV gene expression and selected cellular MiRNAs in lung cancer development.

BACKGROUND: The high mortality rate of lung cancer can be justified that strong need to explore new aspect of tumor biology. Human papillomavirus (HPV) has been detected as risk factor for the development of lung cancer. The aim of this study was to determine the role of HPV and cellular/miRNAs genes expression in the epithelial-mesenchymal transition (EMT) and development of lung cancer. METHODS: In this case-control study, 109 lung cancer tissue and 52 controls were included. We analyzed the presence of HPV infection, its genotypes (in positive samples) and the expression of viral genes (E2, E6 and E7). Also, We examined the expression of celluar factors including (a) p53 and retinoblastoma (Rb) (as anti-carcinogenic genes), (b) EMT related genes, (c) selected miRNAs. RESULTS: Our results reported 51.4% and 23.1% of HPV genome in tumor tissues and control tissues samples, respectively. There was a significant association between the HPV positive status and lung cancer (OR = 3.26, 95% C.I = 1.47-7.02, P = 0.001). HPV type 16 was the most prevalent genotype in tissues. The expression of p53, RB, TIMP1, CCNG-1, E-cad and PTPN13 were decreased while MMP-2 and N-cad were increased in HPV-positive tumor/control tissues compared to HPV-negative tissues. Also, among miRNAs, let-7, miR-23, miR-34, miR-125, miR-146 were downregulated and miR-20, miR-424 were upregulated in HPV-positve tissues compared to HPV-negative tissues. CONCLUSION: This study demonstrated that HPV infection and interaction with cellular genes and miRNAs promote EMT which involved in the lung cancer development.

The detection of canine anti-sperm antibody following parenteral immunization of bitches against homogenized whole sperm.

BACKGROUNDS: The development of a canine-specific method of immunocontraception is one of the non-invasive controlling strategies for humanely decreasing the dog population. This study was aimed to investigate the potential of whole sperm in stimulating the immune system and producing specific anti-sperm antibodies (ASAs) in female dogs. Mature, mixed-breed bitches were subcutaneously immunized with high (200 × 106 cells/mL) and low (100 × 106 cells/mL) doses of sperm vaccine, emulsified with Freund's adjuvants. Booster immunizations were given at weeks 1, 2, 4, and 6, and serum samples were collected at days 0, 14, 28, 42, 63, and 84 prior to each immunization. Reproductive tract samples, including vaginal and uterine lavages, were also collected by flushing each section with sterile PBS at the end of the experiment. Canine anti-sperm antibody titer and specificity in sera and genital secretions were measured using an enzyme-linked immunosorbent assay technique. RESULTS: Specific anti-sperm antibodies were detected in the serum of both high and low dose groups and were significantly higher than those observed in the controls. A high dose of sperm induced elevated immune responses over the low dose antigen. Immunization with a high dose of sperm increased the level of ASAs in the uterine secretions and vaginal secretions significantly. Higher ASAs were observed to have transduced to the uterine lumen compared to the vagina. CONCLUSIONS: Based on the results obtained in this study, parenteral immunization with whole sperm can induce a high level of specific antibodies in the serum and genital secretions of female dogs and the response would be dose-dependent.

CONTEXTE: Le développement d'une méthode d'immunocontraception spécifique à la race canine constitue l'une des stratégies non invasives pour réduire humainement la population canine. Cette étude a pour objectif d'évaluer le potentiel du sperme entier à stimuler le système immunitaire des femelles et à produire des anticorps anti-sperme spécifiques (ASA) chez ces dernières. Des chiennes matures de race croisée sont immunisées par voir sous-cutanée avec soit de fortes doses (200 millions de cellules/mL) soit de faibles doses (100 millions de cellules/mL) de vaccin constitué de sperme entier émulsifié avec des adjuvants de Freund. Des vaccinations de rappel sont faites aux semaines 1, 2, 4 et 6, et des échantillons sanguins sont prélevés aux jours 0, 14, 28, 42, 63 et 84 avant chaque immunisation. Des échantillons de l'appareil reproducteur, incluant des lavages vaginaux et utérins, sont recueillis par flushing de chaque section avec du PBS stérile à la fin de l'expérimentation. Le titre et la spécificité des anticorps anti-sperme entier canin dans le sérum et les sécrétions génitales ont été mesurés par la technique de dosage ELISA. RÉSULTATS: Des anticorps anti-sperme entier spécifiques ont été détectés dans le sérum des femelles immunisées tant avec de faibles que de fortes doses, et de façon significativement plus élevé que chez le groupe témoin. Une dose forte de sperme entier induit des réponses immunitaires élevées par rapport à l'antigène à faible dose. L'immunisation avec une forte dose de sperme entier augmente de façon significative le niveau d'ASA dans les sécrétions utérines et dans les sécrétions vaginales. On a observé que les ASA ont plus été transduits vers la lumière utérine que vers la lumière vaginale. CONCLUSIONS: Basée sur les résultats obtenus dans la présente étude, l'immunisation parentérale par du sperme entier peut induire un taux élevé d'anticorps spécifiques dans le sérum et le sécrétions génitales de chiennes ; et la réponse serait dose-dépendante.