Molecular epidemiology of enteroviruses and predominance of echovirus 30 in an Iranian population with aseptic meningitis

Human enteroviruses are the most prevalent causes of aseptic meningitis worldwide. However, despite such predominancy, defining the enteroviral etiology of aseptic meningitis remains a diagnostic dilemma for the clinician in Iran. Therefore, this study was conducted to characterize the prevalence and clinical significance of enteroviral aseptic meningitis as well as the predominant enterovirus serotypes among patients with aseptic meningitis in the South of Iran. Cerebrospinal fluid (CSF) specimens were obtained from 73 patients with aseptic meningitis (52.1% males and 47.9% females), ages ranging from 1 month to 88 years. Following the extraction of nucleic acid, the detection of enteroviruses was performed by RT-PCR, targeting the 5′ untranslated region of the genome, and sequencing. Enteroviruses were found in 46.6% of samples (34/73). The most predominant serotype was echovirus 30, followed by coxsackievirus B5 and poliovirus type 1 Sabin strain. The enterovirus infections were more prevalent among female patients (58.8%) and those below 5 years of age (52.9%). Although enterovirus infections were observed throughout the year, the infections were more prevalent during autumn with fever as the predominant clinical symptom. The outcomes revealed that enteroviruses are significant causes of aseptic meningitis in the South of Iran, while suspected cases of aseptic meningitis are usually monitored by bacterial culture and biochemical testing of CSF samples. Therefore, the etiology remains unknown in most cases. Molecular detection of viral pathogens should be included as a common approach in the screening of patients with aseptic meningitis to prevent unnecessary treatment and to improve clinical management

Anticancer activity of Sargassum oligocystum water extract against human cancer cell lines

Background and Objectives: Antitumor drug resistance and side effects of antitumor compounds are the most common problems in medicine. Therefore, finding new antitumor agents with low side effects could be interesting. This study was designed to assay antitumor activity of the extract from brown alga Sargassum oligocystum, gathered from Persian Gulf seashore, against K562 and Daudi human cancer cell lines. Materials and Methods: The research was performed as an in vitro study. The effect of the alga extract on proliferation of cell lines were measured by two methods: MTT assay and trypan blue exclusion test. Results and Conclusion: The most effective antitumor activity has been shown at concentrations 500 μg/ml and 400 μg/ml of the alga extract against Daudi and K562 cell lines, respectively. The results showed that the extracts of brown alga Sargassum oligocystum have remarkable antitumor activity against K562 and Daudi cell lines. It is justified to be suggested for further research such as algal extract fractionation and purification and in vivo studies in order to formulate natural compounds with antitumor activities

Antiviral activity of Holothuria sp. a sea cucumber against herpes simplex virus type 1 (HSV-1)

BACKGROUND: Finding the new bioactive compounds with antiviral activity from the natural resources are in interest of many drug discovery scientists. Sea cucumber is among the marine organisms a traditional food item in Asia with different applications in traditional medicine. METHODS: In current study, a cold water extract of the Holothuria sp, one type Persian Gulf’s sea cucumber was evaluated for its antiviral effects against KOS strain of Herpes Simplex Virus tyoe 1 (HSV-1) in cell culture. The half maximal inhibitory concentration (IC50) values were calculated for anti-adsorption activity and intracellular antiviral activity of the crude extract separately. RESULTS: The extract exhibited antiviral activity not only against the virus adsorption to the cells, but also on virus intracellular replication.The CC50 for sea cucumber extract was 32.57 mg/ml. The IC50 values for the inhibition of the virus adsorption to the cells and virus intracellular replication were 120.2 and 189.9 μg/ml respectively. Selectivity index (SI) value for anti-adsorption activity was 189 while that value for the extract’s intracellular antiviral activity was 172. CONCLUSIONS: The results showed that Holothuria sp, water extract has remarkable antiviral effect against HSV-1 in cell culture and it is crucial to investigate the mechanism(s) of action of extract. Moreover, identification of the effective compound(s) within the extract would be necessary for future studies towards developing the new natural antiviral agent against HSV-1

Human Papillomavirus and Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study regarding Tobacco and Alcohol Consumption

We aimed to determine the role of HPV in the pathogenesis and outcome of oropharyngeal squamous cell carcinoma (OSCC) in lifelong nonsmoking and nondrinking patients. A case-case analysis was performed to compare the presence of HPV-DNA in tumor cells of 16 nonsmoking and nondrinking with 16 matched smoking and drinking patients (matching criteria: age at incidence, gender, tumor sublocation, tumor stage). HPV was detected using 2 PCR tests, FISH analysis, and p16INK4A immunostaining. Nonsmoking and nondrinking patients had more HPV-positive tumors than smoking and drinking patients (n = 12; 75% versus n = 2; 13%; P < 0.001). All HPV-positive tumors showed p16INK4A overexpression, and 1 HPV-negative tumor had p16INK4A overexpression, (P < 0.001). Overall survival and disease-specific survival were higher for HPV-positive compared to HPV-negative cases (P = 0.027, P = 0.039, resp.). In conclusion, HPV is strongly associated with OSCC of nonsmoking and nondrinking patients. Specific diagnostic and therapeutic actions should be considered for these patients to achieve a better prognosis

Non-smoking and Non-drinking patients with Head and Neck Squamous Cell Carcinoma, A Distinct Population

195 patients with head and neck squamous cell carcinoma (HNSCC) who had no history of smoking tobacco or drinking alcohol are described. The data is retrieved from the database at the University Medical Center Utrecht which contains information on patient characteristics, risk factors, and tumor classification, including data on development of recurrences, second primary tumors and follow up. During the period 1980-2003, 4404 patients with squamous cell carcinoma of the lip, oral cavity, oropharynx, hypopharynx and larynx were registered. The clinicopathological characteristics of 195 (4.4%) non-smoking and non-drinking patients were analyzed and compared with data for all Dutch patients with HNSCC obtained from the Netherlands Cancer Registry. Non-smoking and non-drinking patients with HNSCC had distinct characteristics. They were typically female, had advanced age at disease presentation and had tumors mainly of the oral cavity. The incidence of second primary tumors (SPTs) was high, mainly occurring in the oral cavity. The prognostic relevance of tobacco and alcohol for patients with HNSCC was addressed. To this end, univariate and multivariate survival analysis were performed for 2012 patients, including 183 non-smoking and non-drinking patients and 1829 patients who consumed both tobacco and alcohol. HNSCC-specific survival was not significantly different for patients who smoked and drank and those who did not. Overall survival was significantly affected by tobacco and alcohol. The expression of tumor suppressor gene p53 and proliferation marker Ki-67 in non-tumorous (tumor-adjacent) mucosal epithelial cells were analyzed to study whether biomarker expression is associated with a history of smoking and drinking and with single and multiple HNSCC. Non-smoking and non-drinking patients with multiple and single tumors, smoking and drinking patients with multiple and single tumors were selected. p53 expression was significantly higher in users of tobacco and alcohol than in non-users. Ki-67 expression was not affected by tobacco and alcohol use. Both Ki-67 and p53 were similarly expressed in the groups with single and multiple tumors and thus not significantly related to the number of tumors. Hence, the significance of these proteins as biomarkers indicating premalignant mucosal alterations in HNSCC was considered as doubtful. A case-case analysis was performed to compare presence of Human papilloma virus (HPV) in tumor cells of 16 non-smoking and non-drinking with 16 matched smoking and drinking patients with oropharyngeal localized tumors. Non-smoking and non-drinking patients had more HPV-positive tumors than smoking and drinking patients. Overall survival and disease-specific survival were better for HPV-positive compared to HPV-negative cases. DNA microarray detected 49 differentially expressed genes for non-smoking and non-drinking patients compared to smoking and drinking patients. Amongst others, 7 genes related to Interferon-γ (IFN-γ) were downregulated. These genes play an important role in controlling the immune response upon pathogenic challenge. Moreover, 2 genes linked to NFKB pathway, which is a key regulator in TRD/TRAIL-mediated apoptosis were upregulated. Our findings suggest that the non-smoking and non-drinking patients with HNSCC have a different immune response to their tumor when compared to their smoking and drinking counterparts which may reflect a different underlying carcinogenetic mechanism

Prevalence, risk factors and molecular evaluation of hepatitis E virus infection among pregnant women resident in the northern shores of Persian Gulf, Iran

BACKGROUND: Although Iran is reported to be an endemic country for hepatitis E virus (HEV), data on the prevalence of HEV infection among pregnant women are scarce and the epidemiology of HEV is unknown in most parts of the country. Therefore, this study was conducted to elucidate the prevalence, risk factors and genotypic pattern of HEV infection among pregnant women resident in the northern shores of Persian Gulf. This is the first report on the epidemiology of HEV infection among pregnant women in this territory. METHODS: From October 2016 to May 2017, 1331 pregnant women participated in this study. The mean age +/- SD of participants was 27.93+/-5.7 years with a range of 14-45 years. Serum samples of pregnant women were screened for the presence of anti-HEV total antibodies, anti-HEV IgG and anti-HEV IgM using commercially available ELISA kits (DIA.PRO, Milan, Italy). All anti-HEV IgG and anti-HEV IgM positive samples were tested for HEV RNA using two independent reverse transcriptase polymerase chain reaction (RT-PCR) assays, targeting ORF2 and ORF3 of HEV genome. In addition, 92 anti-HEV seronegative samples as well as 50 pooled seronegative samples were evaluated by two independent RT-PCR assays for validation of results. RESULTS: Of the 1331 pregnant women, 84 women (6.3%, 95% CI: 5.1%-7.7%) were positive for anti-HEV antibodies, of which 83 women had anti-HEV IgG, and 11 women (0.83%, 95% CI: 0.47%-1.47%) had anti-HEV IgM. The highest rate of HEV seroprevalence was observed among Afghan immigrants (68.0%), uneducated pregnant women (46.51%) and those residents in Bushehr city (8.75%). All anti-HEV IgG and/or IgM positive samples were found to be negative for HEV RNA. In addition, all of the evaluated anti-HEV seronegative samples were negative for HEV RNA. HEV seropositivity among pregnant women was statistically associated with age, ethnicity, place of residence, number of pregnancies, and level of education. So that, low education levels, Afghan, residence in Bushehr city, age group >34 years, and more parities were risk factors for exposure to HEV. In contrast, HEV seropositivity was not associated with stage of gestation, history of abortion, and time of sampling. CONCLUSION: The northern shores of Persian Gulf in Iran, with HEV seroprevalence of 6.3%, can be classified as an endemic geographical region for hepatitis E, and residents of Bushehr city, Afghan immigrants and uneducated women are the main at-risk populations in this territory

Prevalence and Predominant Genotype of Hepatitis C Virus Infection and Associated Risk Factors among Pregnant Women in Iran

Objective. Knowledge regarding the prevalence and risk factors of hepatitis C virus (HCV) infection among pregnant women can give clue to health care providers regarding the appropriate management of HCV infection. Therefore, this study was conducted to determine the prevalence, genotypic pattern, and risk factors of HCV infection among pregnant women in the northern shores of the Persian Gulf, south of Iran. Methods. From January 2018 to June 2019, serum samples were obtained from 1425 pregnant women, ages ranging from 14 to 46 years (28.1±5.99). Serum samples were tested for detection of anti-HCV antibodies using an enzyme-linked immunosorbent assay (ELISA) (HCV Ab ELISA kit, Dia.Pro, Milan, Italy). Following the extraction of nucleic acid, the molecular evaluation of HCV infection was performed by seminested reverse transcriptase-polymerase chain reaction assay (RT-PCR), targeting the 5′ untranslated region (5′UTR) and core of HCV genome and sequencing. Results. Of the 1425 pregnant women, 19 women (1.33%, 95% CI: 0.85%-2.07%) were positive for anti-HCV antibodies. The majority of HCV-seropositive women were in the third trimester of pregnancy, educated, and had a history of blood transfusion, abortion, surgery, or dentistry. Moreover, Arab and Fars pregnant women and those aged >39 years had the highest rate of HCV seroprevalence. Nevertheless, none of these variables were significantly associated with HCV seropositivity. In contrast, HCV seropositivity was associated with place of residency, so that residents of Khormuj city had significantly higher HCV seroprevalence compared to the residents of other cities (OR: 7.05; 95% CI: 1.75-28.39; P=0.006). According to the molecular evaluation, 9 of the 19 HCV-seropositive pregnant women (47.37%) had HCV viremia with genotype 3a. Conclusion. This study reports the HCV prevalence of 1.33% for anti-HCV antibodies and 0.63% for HCV RNA among pregnant women in the south of Iran. Considering the asymptomatic nature of chronic HCV infection and the fact that vertical transmission is possible in women with detectable viremia, therefore, screening of women before pregnancy is recommended to reduce the risk of HCV infection and its complications during pregnancy