Evaluation of angiotensin converting enzyme 2 (ACE2), angiotensin II (Ang II), miR-141-3p, and miR-421 levels in SARS-CoV-2 patients: a case-control study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that uses angiotensin converting enzyme 2 (ACE2), a pivotal member of the renin-angiotensin system (RAS), as its cell-entry receptor. Another member of the RAS, angiotensin II (Ang II), is the major biologically active component in this system. There is growing evidence suggesting that serum miRNAs could serve as prognostic biomarkers for SARS-CoV-2 infection and regulate ACE2 expression. Therefore, the aim of this study is to evaluate the changes in the serum levels of sACE2 and Ang II, as well as the expression level of miR-141-3p and miR-421 in SARS-CoV-2 positive and negative subjects. METHODS: In the present study, the serum levels of sACE2 and Ang II were measured in 94 SARS-CoV-2 positive patients and 94 SARS-CoV-2 negative subjects with some symptoms similar to those of SARS-CoV-2 positive patients using the ELISA method. In addition, the expression level of miR-141-3p and miR-421 as ACE2 regulators and biomarkers was evaluated using quantitative real-time PCR (qRT-PCR) method. RESULTS: The mean serum sACE2 concentration in the SARS-CoV-2-positive group was 3.268 ± 0.410 ng/ml, whereas in the SARS-CoV-2 negative group, it was 3.564 ± 0.437 ng/ml. Additionally, the mean serum Ang II level in the SARS-CoV-2 positive and negative groups were 60.67 ± 6.192 ng/L and 67.97 ± 6.837 ng/L, respectively. However, there was no significant difference in the serum levels of sACE2 (P value: 0.516) and Ang II (P value: 0.134) between the SARS-CoV-2 positive and negative groups. Meanwhile, our findings indicated that the expression levels of miR-141-3p and miR-421 in SARS-CoV-2 positive group were significantly lower and higher than SARS-CoV-2 negative group, respectively (P value < 0.001). CONCLUSIONS: Taken together, the results of this study showed that the serum levels of sACE2 and Ang II in SARS-CoV-2 positive and negative subjects were not significantly different, but the expression levels of miR-141-3p and miR-421 were altered in SARS-CoV-2 positive patients which need more investigation to be used as biomarkers for COVID-19 diagnosis.

Aflatoxin B1 and viruses' combined pathogenesis: A mini systematics review of invitro and invivo studies.

INTRODUCTION: The combined pathogenesis of Aflatoxin B1 (AFB1) and several viruses such as HBV, EBV and influenza virus have been investigated yet the molecular mechanism of their interaction and possible synergistic effects is not fully understood. OBJECTIVES: The aim of the current systematic review was to review in-vitro and in-vivo studies investigating the combined pathogenesis of aflatoxins and viruses. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PECO (Population, Exposure, Comparator, and Outcome) criteria for invitro and invivo studies were used to evaluate the eligibility of the studies for systematic review. RESULTS: 21 studies were eligible for qualitative analysis based on the inclusion criteria. Of all the included studies, 9 (42.9 %) were invivo, 7 (33.3 %) were invitro-invivo and 5(23.8) articles conducted only invitro assay. Furthermore 14 (66.6 %) article explored hepatitis B virus (HBV) combination with AFB1, 4 (19 %) studied influenza A virus (SIV), 2 (9.7 %) were about Epstein-Barr virus (EBV) and only 1 (4.7 %) included hepatitis C virus (HCV). CONCLUSION: The limited collected evidence suggests that AFB1 enhanced EBV and influenza virus pathogenesis. AFB1 also operated as a cofactor for HBV and EBV-mediated carcinogenesis. On the other hand HBV and HCV also induced AFB-1 carcinogenesis. Due to the limited amount of included studies and the inconsistency of their results further studies especially on HBV and SIV are essential for better understanding of their combined mechanisms.

P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening.

BACKGROUND: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer. METHODS: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details. RESULTS: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16. CONCLUSION: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.

Relative Frequency of Blood-Borne Viruses in Hemodialysis-Dependent and Kidney Transplant Recipients in Iran.

BACKGROUND: Hemodialysis (HD) patients and kidney transplant (KT) recipients are exposed to be infected by blood-borne viruses (BBVs). Current study was conducted to evaluate the prevalence of BBVs in HD and KT patients in the whole Iranian population. METHODS: From Jan 2016 to Dec 2017, 174 hemodialysis and 139 kidney transplant recipients enrolled in this survey. After blood sampling, serum samples were detected for HBV, HCV, HCMV, HIV and HTLV antibodies. Seropositive samples confirmed by Polymerase chain reaction (PCR) method. RESULTS: Overall, 6 (3.44%) and 3 (2.15%) of hemodialysis-dependent and transplantation patients had evidence of HCV infection, whereas no patients were HIV and HBV positive, two cases (1.14%) of hemodialysis and one case (0.71%) of transplantation patients demonstrated the HTLV-1 infection. 52 (37.4%) of patients received graft were positive for HCMV antibody. In addition, our study showed a co-infection of HCMV with HCV (3 patients, 2.15%) in transplantation patients. CONCLUSION: Prevalence of BBVs infection was lower in comparison to the previous studies. The current strict infection control practices in Iran appear to be effective in limiting dialysis and related infections after transplantation. Because BBVs infections constantly occur especially in dialysis and after transplantation units, our data will be useful to build a new strategic plan for the elimination of BBVs infection in kidney therapycenters.

Comparison of Snail1, ZEB1, E-Cadherin Expression Levels in HPV-Induced Cervical Cancer.

BACKGROUND: Molecular profiling techniques are the rapid detection of biomarkers in the human papillomavirus (HPV) infected cells. We aimed to measure the expression level of three cell factors including Snail1, ZEB-1, and E-cadherin in cervical cancer (CC), precancerous and healthy samples, simultaneously, to find potential biomarkers. METHODS: The expression level of the mentioned cell factors were investigated in 72 CC patients, precancerous patients, and healthy controls by using Real-Time PCR. RESULTS: The results demonstrated a significant reduction in the expression level of E-cadherin in cancer and precancerous cases than that in healthy cases; whereas the expression level of ZEB-1 and Snail1 were upregulated in cancer and precancerous samples. The receiver operating characteristic (ROC) analyses shows the highest AUC value emerged for Snail1: 1(95% CI: 1-1) in comparing CC and healthy groups with a sensitivity of 100.0 % and specificity of 100.0%. CONCLUSION: The molecular biomarker Snail1 may be helpful to early diagnosis and prognosis of CC in the HPV-infected human populations. Considering the increased expression level of Snail1 in cancer and precancerous tissue compared to healthy tissue as well as the area under the ROC curve, Snail1 can be used for early detection of CC.

Anoikis resistance and oncoviruses.

Anoikis is known as a special type of programmed cell death which occurs in response to loss of correct cell-extracellular matrix (ECM) connections. This process could be as pivotal event in normal development and tissue homeostasis and found as important mechanism in cancer invasiveness and metastasis. The persistent infection with oncoviruses including EBV (Epstein Bar virus), HPV (Human Papillomaviruses), HBV (Hepatitis B virus), KSHV (Human herpesvirus 8), HTLV-1 (Human T-lymphotropic virus-1), and HCV (Hepatitis C virus) accounted as one of main risk factor for cancer progression. Some of them play critical roles in metastasis, especially in anoikis resistance which could contribute to metastasis of tumor cells. The better understanding of effects of oncoviruses on anoikis could contribute to finding of effective therapeutic platforms for treatment of virus-associated cancers. This paper highlighted effects of these oncoviruses on anoikis protection in cancer.