Masoumeh Tavakoli-Yaraki

Prevalence of human respiratory syncytial virus circulating in Iran.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and is associated with a great burden on patients, parents, and society. While no treatment is yet available, results from recent phase 2 clinical trials of cell-entry inhibitors and RSV vaccines are promising. To prepare for introduction of these novel therapeutics, good understanding of its molecular epidemiology and continuous RSV surveillance data are necessary. This paper provides an overview of RSV prevalence and genotype distribution in Iran from 1996 to 2013. This meta-analysis includes 21 published studies. In total, 775 (18.7%) of 4140 respiratory specimens were positive for RSV infection. The male-female ratio of RSV-positive patients was 1.5:1. Significant peaks of RSV infection were detected during the cold season (November-March). RSV infection was mainly observed in patients <2 years of age. Phylogenetic studies showed that genotypes GA1, GA2, GA5, and BA co-circulated in Iran in 2007-2013. This review highlights the necessity of introducing standard molecular surveillance programs to inform the epidemiological, clinical, and pathological characteristics of various RSV genotypes. Improved understanding of the molecular epidemiology will be useful for development of novel RSV therapeutics.

A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?

Cancer stem cell (CSC) markers could serve as potential prognostic procedure. This study is aimed to investigate the local expression of doublecortin-like kinase 1 (DCLK1) and Lgr5 in colorectal cancer tissues (CRC) at both protein and messenger RNA (mRNA) level, followed by providing a comparison of the local and circulating expression pattern of these markers, based on our present and previous study. The mRNA expression level of DCLK1 and Lgr5 was evaluated using comparative real-time PCR method applying 58 fresh tumor tissues and their correspondent normal margins. Immunohistochemistry was applied to analyze the protein expression level of DCLK1 and Lgr5 in paraffin-embedded CRC tissues. The correlation of DCLK1 and Lgr5 expression pattern with clinicopathological characteristics was assessed. A higher mRNA expression level of DCLK1 (3.28-fold change, p < 0.001) and Lgr5 (2.29-fold change, p < 0.001) was observed in CRC fresh tissues compared to the normal adjacent margins, and the expression level was higher in patients with higher grade and stages of disease and patients who underwent neoadjuvant chemoradiotherapy (CRT). The protein expression level of DCLK1 and Lgr5 was also increased significantly in tumor tissues compared to normal colon tissues which were positively correlated to tumor stage and grade and neoadjuvant CRT. Taken together, the results of protein analysis were in accordance with mRNA assessment. The local expression pattern of DCLK1 and Lgr5 was also in accordance with their expression level in circulation. However, some minor inconsistencies were observed which may be attributed to several factors including the possible effect of CRT on CSC reprogramming.

The role of microRNAs in respiratory viral infection: friend or foe?

MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs in host–pathogen interactions. Aberrant miRNA expression seems to play a central role in the pathology of several respiratory viruses, promoting development and progression of infection. miRNAs may thus serve as therapeutic and prognostic factors for respiratory viral infectious disease caused by a variety of agents. We present a comprehensive review of recent findings related to the role of miRNAs in different respiratory viral infections and discuss possible therapeutic opportunities aiming to attenuate the burden of viral infections. Our review supports the emerging concept that cellular and viral‐encoded miRNAs might be broadly implicated in human respiratory viral infections, with either positive or negative effects on virus life cycle. Copyright

Effects of cannabinoids and their receptors on viral infections

Cannabinoids, the active ingredient in marijuana, and their derivatives have received remarkable attention in the last two decades because they can affect tumor growth and metastasis. There is a large body of evidence from in vivo and in vitro models showing that cannabinoids and their receptors influence the immune system, viral pathogenesis, and viral replication. The present study reviews current insights into the role of cannabinoids and their receptors on viral infections. The results reported here indicate that cannabinoids and their receptors have different sequels for viral infection. Although activation or inhibition of cannabinoid receptors in the majority of viral infections are proper targets for development of safe and effective treatments, caution is required before using pharmaceutical cannabinoids as a treatment agent for patients with viral infections. J. Med. Virol. 88:1–12, 2016.

Evaluation of the expression level of 12/15 lipoxygenase and the related inflammatory factors (CCL5, CCL3) in respiratory syncytial virus infection in mice model

Human respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and imposes a great burden on patients, parents, and society. Disease is thought to be caused, at least partially, by an excessive immune response. Pulmonary leukocyte infiltration is the result of a coordinated expression of diverse chemokines with distinct cellular specificities. Lipoxygenases (LOXs), as a key enzyme catalyzing deoxygenation of poly unsaturated fatty acids, regulate inflammation and have been suggested to play an important role in the immune response in viral infection. To expand our understanding on the possible role of LOX in respiratory viral infection, we studied the 12/15- lipoxygenase expression in RSV-related airway inflammation, and the related inflammatory chemokines, Chemokine (C-C motif) ligand 5 (CCL5) and Chemokine (C-C motif) ligand 3(CC L3) in both lung tissue and Bronchoalveolar lavage (BAL) fluid during experimental RSV infection. RSV infection induced mRNA expression of CCL5 and CCL3 in both BAL and lung tissue cells. In addition RSV infection enhanced expression of 12/15-LOX in both BAL and lung cells. In conclusion, we confirm that RSV infection leads to the increased expression of 12/15 LOX and the related chemokines CCL5 and CCL3 in BAL fluid and lung tissue cells suggesting that the 12/15 LOX pathway could serve as a candidate target for prevention and treatment of RSV infection.

Sodium butyrate promotes apoptosis in breast cancer cells through reactive oxygen species (ROS) formation and mitochondrial impairment.

BackgroundSodium butyrate (NaBu) is a short-chain fatty acid which serves as a histon deacetylase inhibitor and has received considerable interest as a possible regulator of cancer cell death. The regulatory effect of NaBu on cancer cell growth or death has yet to be illustrated in many cancers including breast cancer. This study is aimed to elucidate the possible effect of NaBu on regulation of breast cancer growth and apoptosis.MethodsThe cytotoxic effect of NaBu on the growth of breast cancer cells (MCF-7 and MDA-MB-468) and normal breast cells (MCF-10A) was determined using MTT assay. Annexin-V-FITC staining and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry, the level of mitochondrial membrane potential (Δψm), Reactive oxygen species (ROS)formation and caspase activity were determined accordingly.ResultsBased on our data, NaBu induced a dose and time-dependent cell toxicity in breast cancer cells which was related to the cell cycle arrest and induction of apoptosis. The impact of NaBu on MCF-10A cell toxicity, cell cycle distribution and apoptosis was inconsiderable. NaBu-elicited apoptosis was accompanied by the elevated level of ROS, increased caspase activity and reduced mitochondrial membrane potential (Δψm) in MCF-7 and MDA-MB-468 cells and with no effect on the above mentioned factors in MCF-10A cells.ConclusionsOur study provided insight in to the role of NaBu on the regulation of breast cancer cell growth and lighten up the pro-apoptotic activity of NaBu.

Opioids and Viral Infections : A Double-Edged Sword

Opioids and their receptors have received remarkable attention because they have the ability to alter immune function, which affects disease progression. In vitro and in vivo findings as well as observations in humans indicate that opioids and their receptors positively or negatively affect viral replication and virus-mediated pathology. The present study reviews recent insights in the role of opioids and their receptors in viral infections and discusses possible therapeutic opportunities. This review supports the emerging concept that opioids and their receptors have both favorable and unfavorable effects on viral disease, depending on the type of virus. Targeting of the opioid system is a potential option for developing effective therapies; however caution is required in relation to the beneficial functions of opioid systems.

Involvement of 15-lipoxygenase-1 in the regulation of breast cancer cell death induced by sodium butyrate.

Abstract15-Lipoxygenase-1 (15-Lox-1) as a member of fatty acid dioxygenases family has received considerable attention as an effector of cancer cell growth. The relevance of sodium butyrate on 15-Lox-1 pathway has not been determined in breast cancer. This study is aimed to investigate the possible involvement of 15-Lox-1 in the regulation of breast cancer cell growth by sodium butyrate. MTT assay was used to assess the cytotoxicity effect and Annexin-V-FITC staining was applied for detection of apoptosis using flow cytometry. The involvement of 15-Lox-1 was examined using 15-Lox-1 specific inhibitor and enzyme gene expression level and activity was further analyzed by Real-time PCR and measurement of 13(S)-HODE. The results revealed that sodium butyrate increased the expression of 15-Lox-1 and production of 13(S)HODE. 15-Lox-1 was also involved in the sodium butyrate-induced breast cancer cell cytotoxicity and apoptosis. This study provided more evidences on the positive effectiveness of 15-Lox-1/13(S)-HODE on controlling growth of breast cancer cells.

Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice

ABSTRACT An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI). The frequency distribution of respiratory syncytial virus (RSV)-the main cause of severe cases of bronchiolitis and pneumonia in children-was studied in all collected samples. The mechanism through which CB2 affects clinical outcomes in case of RSV infection was studied in Balb/c mice model using AM630 as a CB2 antagonist. The potential therapeutic effect of CB2 activation during RSV infection was studied using a selective agonist, JWH133. The CB2 Q63R variation was associated with increased risk of hospitalization in children with ARTI. Children carrying the QQ genotype were more prone to developing severe ARTI (OR = 3.275, 95% CI: 1.221–8.705; p = 0.019). Of all the children enrolled in the study, 83 patients (46.1%) were found positive for RSV infection. The associated risk of developing severe ARTI following RSV infection increased more than two-fold in children carrying the Q allele (OR = 2.148, 95% CI: 1.092–4.224; p = 0.026). In mice, the blockade of CB2 by AM630 during RSV infection enhanced the influx of BAL cells and production of cytokines/chemokines while exaggerating lung pathology. CB2 activation by JWH133 reduces the influx of BAL cells and production of cytokines/chemokines while alleviating lung pathology. Collectively, CB2 is associated with RSV severity during infancy and may serve as a therapeutic target in RSV infection through the alleviation of virus-associated immunopathology.

A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis

Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease, with unknown etiology. Vitamins, as important micronutrients playing different roles in body, seem to be important in MS pathogenesis. In vitro, in vivo and human studies, supports the protective role of some vitamins in MS occurrence or progression. Current study reviews recent insights and reports about the importance of vitamins in MS incidence or progression. In accordance, the importance of all water and fat-soluble vitamins in MS pathogenesis based on observational studies in human population and their role in the function of immune system as well as possible therapeutic opportunities are discussed in depth throughout this review.