Oncolytic Newcastle disease virus reduces growth of cervical cancer cell by inducing apoptosis.

Although Oncolytic viruses have been regarded as a promising tool for targeted therapy of cancer, accomplishing high efficacy and specificity with this strategy is challenging. Oncolytic virotherapy is one of the novel therapeutic methods recently used for the therapy of human malignancies. Cervical cancer is on the major public health problem and the second most common cause of cancer death among females in less developed countries. The aim of this study was mainly to determine the apoptosis effect of oncolytic Newcastle disease virus (NDV) in TC-1 cell line. In the current study, the oncolytic NDV, vaccine strain LaSota, was used to infect murine TC-1 cells of human papillomavirus (HPV)-associated carcinoma which expressing human papillomavirus 16 (HPV-16) E6/E7 antigens in vitro. The effectiveness of NDV for cervical cancer cell line was investigated by evaluating the antitumor activity of oncolytic NDV and the involved mechanisms. Antitumor activities of oncolytic NDV were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. In addition, molecular changes of early stage of apoptosis and the role of reactive oxygen species (ROS) were analyzed by flow cytometry and Western Blot in NDV-treated TC-1 cells. The results showed that NDV treatment significantly decreased the viability of a TC-1 cell line and suppressed the growth by inducing apoptotic cell death. In addition, we demonstrated that NDV-induced apoptosis of TC-1 cells is mediated by ROS production. In summary, our findings suggest that oncolytic NDV is a possible therapeutic candidate as a selective antitumor agent for the treatment of cervical cancer.

The Occurrence and Risk Assessment of Exposure to Aflatoxin M1 in Ultra-High Temperature and Pasteurized Milk in Hamadan Province of Iran.

OBJECTIVES: Aflatoxins are a category of poisonous compounds found in most plants, milk and dairy products. The present research was carried out to detect the presence of aflatoxin M1 (AFM1) in samples of milk collected from Hamadan province, Iran. METHODS: Twenty five samples of ultra-high temperature (UHT) and 63 samples of pasteurized milk were collected and the amount of AFM1 was measured by an Enzyme-Linked Immunosorbent Assay method. In addition, the estimated daily intake (EDI) and hazard index (HI) of AFM1 was determined by the following equations:(EDI= mean concentration of AFM1 × daily consumption of milk/body weight; HI= EDI/Tolerance Daily Intake). RESULTS: AFM1 was detected in 21 (84%) UHT milk samples and in 55 (87.30%) pasteurized milk samples. Seven (28%) samples of UHT and 21 (33.33%) pasteurized milk samples had higher AFM1 content than the limit allowed in the European Union and Iranian National Standard Limits (0.05 µg/kg). None of the samples exceeded the US Food and Drug Administration limit (0.5 µg/kg) for AFM1. EDI and HI for AM1 through milk were 0.107 ng/kg body weight/day, and 0.535, respectively. CONCLUSION: A significant percentage of milk produced by different factories in Iran (84% of UHT and 87.3% of pasteurized milk) was contaminated with AFM1. Therefore, more control and monitoring of livestock feeding in dairy companies may help reduce milk contamination with AFM1. As the HI value was lower than 1, it can be assumed that there was no risk of developing liver cancer due to milk consumption.

Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains.

OBJECTIVES: Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans. METHODS: Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus. RESULTS: Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue. CONCLUSION: These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease.

Factors that Correlate with Poor Glycemic Control in Type 2 Diabetes Mellitus Patients with Complications.

OBJECTIVES: Inadequate glycemic control amongst patients with Type 2 diabetes mellitus (T2DM) indicates a major public health problem and a significant risk factor for the progression and complications caused by diabetes. Glycemic control is the main therapeutic objective for the prevention of organ damage and other complications arising from diabetes. METHODS: This was a retrospective observational study of T2DM patients with complications, who were aged 40 years and older. The study was conducted retrospectively on medical records (in-patient and out-patient) obtained from a South Indian teaching hospital, Manipal, India. The patients included in the study had fasting blood sugar, postprandial blood sugar and HbA1c measured at least twice during follow-ups the previous year. Patients' HbA1c levels were categorized into good control ≤7% (≤53mmol/mol), and poor control >7% (>53mmol/mol), and patients' characteristics were analyzed. RESULTS: A total of 657 patients were included in the study. The mean age was 59.67 (SD = 9.617) years, with 152 (23.1%) females and 505 (76.9%) males, and 514 (78.2%) patients had poor glycemic control. Most of the patients were on insulin mono-therapy [n = 271 (42.1%)], about a third of the patients were on combination therapy that included an oral hypoglycemic agent and insulin [n = 236 (36.6%)]. Patients with a history of more than 10 years of diabetes [n = 293 (44.6%)], had a family history of diabetes [n = 256 (39%)] and obesity [n = 95 (14.5%)], all had poor glycemic control. CONCLUSION: This present study indicated a significant association of gender (female), age, high-density lipoprotein level, duration of diabetes and type of medication, with poor glycemic control in T2DM patients that had secondary medical complications.

α:Non-α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea.

OBJECTIVES: To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or ß-like) synthesis. METHODS: A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg·day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. RESULTS: Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. CONCLUSIONS: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major.

Aflatoxin M1 in raw cow and buffalo milk in Shush city of Iran.

Aflatoxin M1 (AFM1) contamination is evaluated in 120 samples of raw milk from cow and buffalo (60 each), collected randomly in the Shush (southwest Iran). Enzyme-linked immunoabsorbent assay (ELISA) was applied to analyse AFM1 in the samples. AFM1 was detected in 44 (69%) raw cow milk samples with a mean of 55 ng/l at a range of 3.6-419 ng/l) and in 46 (79%) raw buffalo milk samples with a mean of 116 ng/l at a range of 13-423 ng/l. In all samples, the AFM1 concentration was lower than the Iranian national standard and FDA limit of 500 ng/l. According to the European Union and Codex Alimentarius Commission, 18 (28%) and 32 (52%) of cow and buffalo raw milk samples are above the 50 ng/l limit, respectively. Results showed that AFM1 contamination of raw milk could pose a problem for public health, since all age groups, including infants and children, consume this product.

Optimization of multiple shoot induction and plant regeneration in Indian barley (Hordeum vulgare) cultivars using mature embryos.

Barley is the fourth most important crop in the world. Development of a regeneration system using immature embryos is both time consuming and laborious. The present study was initiated with a view to develop a regeneration system in six genotypes of Indian barley (Hordeum vulgare) cultivars as a prerequisite to transformation. The mature embryos were excised from seeds and cultured on MS medium supplemented with high and low concentrations of cytokinins and auxins respectively. The MS medium containing 3 mg/L N(6)-benzylaminopurine (BA) and 0.5 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) was found to be the most effective for multiple shoot formation in HOR7231 cultivar that could produce 12 shoots per explant. The other cultivars HOR4409 and HOR3844 produced a minimum number of adventitious shoots (1.33 and 1.67 respectively) on MS medium supplemented with 1 mg/L BA and 0.3 mg/L 2,4-D. The elongated shoots were separated and successfully rooted on MS medium containing 1 mg/L indole-3-acetic acid (IAA). The response of different barley cultivars was found to be varying with respect to multiple shoot production. This is the first report of multiple shoot induction and plantlet regeneration in Indian cultivar of barley which would be useful for genetic transformation.