azita zadeh

Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient’s cells. In this paper we examine the results of an investigational assessment of secukinumab gene therapy. In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the approved secukinumab as the standard reference. Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene therapies. In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases.

The “results section” of a scientific paper provides the results related to all measurements and outcomes that have been posted earlier in the materials and methods section. This section consists of text, figures, and tables presenting detailed data and facts without interpretation and discussion. Results may be presented in chronological order, general to specific order, most to least important order, or may be organized according to the topic/study groups or experiment/measured parameters. The primary content of this section includes the most relevant results that correspond to the central question stated in the introduction section, whether they support the hypothesis or not. Findings related to secondary outcomes and subgroup analyses may be reported in this section. All results should be presented in a clear, concise, and sensible manner. In this review, we discuss the function, content, and organization of the “results section,” as well as the principles and the most common tips for the writing of this section.

The materials and methods (M&M) section is the heart of a scientific paper and is subject to initial screening of the editor to decide whether the manuscript should be sent for external review. If the M&M section of a scientific paper be considered as a recipe, its ingredients would be who, what, when, where, how, and why. M&M should effectively respond to the study question/hypothesis using the following basic elements including materials, study design, study population/subjects or animals, methods of measurements/assessments, and statistical analysis. A well-organized M&M permits other scientists to evaluate the study findings and repeat the experiments. Although there are several disciplinary differences in the M&M, similar dos and don’ts may be considered to organize a well-written M&M. Briefly, authors need to provide clear-cut, adequate, and detailed information in the M&M section. In this review, the structure, the principles, and the most common recommendations for writing the M&M section are provided, both in general and study-specific; these could help authors effectively prepare the M&M section of a scientific biomedical manuscript.

In the late 1990s the non-communicable diseases were becoming increasingly more prevalent and a significant proportion of evidence in this regard had originated from industrialized “Western” countries. This had led to a landscape where most national and local health decisions regarding non-communicable diseases (NCDs) were informed by data generated elsewhere. Iran, as a large country in the Middle East was no exception and was going through significant population growth and urban development at the time. An initiative by the Iranian National Scientific Research Council funded an idea that was aimed at delineating the local epidemiology of NCDs and their risk factors in a manner that was unprecedented. The result was Tehran Lipid and Glucose Study (TLGS), the first and longest running cohort of its sort in Iran. Initial data out of TLGS reported the characteristics of 15005 people aged over 3 years in a representative population of Tehranians. Additionally, distribution and prevalence of cardiovascular risk factors among the study population were characterized. This population was selected through a multistage stratified cluster random sampling technique from the population of district 13 in Tehran. In addition, TLGS gave rise to a great deal of important and highly effective initial findings on national cut-off points for various variables, information about nutrition, hypertension, dyslipoproteinemia, and metabolic syndrome. TLGS also generated information about metabolic health indicators among children and adolescents. Here we present a brief overview of rationale, design, and initial findings of TLGS.

Context: The Tehran lipid and glucose study (TLGS) is one of the oldest population-based longitudinal cohort studies, providing knowledge about the incidence and risk factors of some non-communicable diseases (NCDs) in West Asia which hitherto was relatively scarce. We reviewed the methods and results related to the outcome measurements of this study. Evidence Acquisition: We reviewed all the TLGS papers which reported the incidence of NCDs. The TLGS was initiated in 1999 - 2001 on a population in district no. 13 of Tehran with the same age distribution of the overall Tehran population and with a middle socioeconomic status. Totally, 15005 individuals, aged ≥ 3 years, participated in the first examination; reexaminations were conducted in a triennial manner and 3550 individuals were added in the second examination. All participants were also followed up annually and asked about any medical event leading to hospitalization or death. A part of participants was assigned to an educational program for lifestyle modification. High incidence of cardiovascular disease (CVD), premature CVD, diabetes and hypertension (around 19, 6, 10 and 31 in men and 11, 5, 11 and 29 in women per 1000 person-year, respectively) besides the high incidence of pre-diabetes and pre-hypertension (around 46 and 76 in men and 37 and 49 in women per 1000 person-year, respectively) showed a worrying situation. Fortunately, the results of the community interventions were promising with around 20% reduction in the risk of metabolic syndrome up to six years. These precise detections of different outcomes in the TLGS provided valuable evidences for prediction and prevention of NCDs in Iran with some novelties in the middle-income countries in the world. The Tehran thyroid study (TTS) and the Tehran cardiometabolic genetic study (TCGS), conducted in the framework of the TLGS, are among few studies aiming to determine the natural course of thyroid function and to identify patterns of genetic polymorphisms related to cardiometabolic outcomes, respectively.

Context: Tehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects. Evidence Acquisition: For all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH). This review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5). Considering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics’ data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.

Tehran Lipid and Glucose Study (TLGS), an epidemiological study of non-communicable disease with 20 years follow up in a developing country in nutrition transition is a unique study in 15000 family based individuals, 3 - 75 years of age in a part of large city of Tehran. The success rate of recruitment for 20 years, intervention for lifestyle change, and thyroid, reproduction and cardiometabolic genetic studies derived from TLGS have paved suitable path towards precision medicine. In this review, baseline findings and changes of risk factors for the development of NCD including body weight, nutrition, physical activity, blood pressure, tobacco smoking, serum glucose and serum lipids as well as metabolic syndrome, chronic kidney disease, quality of life and biochemical findings in TLGS cohort have been summarized. The results of community based intervention for lifestyle change caused decreases in the prevalence of metabolic syndrome and the incidence of diabetes. It is concluded that TLGS has served as a model for other cohort studies in Iran and the region; it has helped to mobilize scientists in developing countries; it has established locally needed definitions of NCD variables; has served as a model for cohort studies in developing countries in nutrition transition with all socioeconomic constraints and has helped manpower education and development of local CVD risk scores for implementation of NCD management.

Environmental factors and hormonal disorders during prenatal life can impair the evolution and differentiation of fetus’s reproductive system. The aim of this study was to the examination of sperm quality and testis tissue in adult rats that had exposed to exogenous testosterone during their prenatal life.
Pregnant rats divided into two experimental and control groups. In experimental group, pregnant rats daily were subcutaneously injected with 3 mg exogenous testosterone during gestational days 16-19, and controls received solvent. The reproductive system was examined in male offspring of these animals after puberty. Data analysis was performed by using the SPSS software (version 15). Distributions between groups are compared by using the Mann-Whitney test.
In the offspring of experimental group, motility and the number of sperm were significantly decreased (P The present study showed that prenatal exposure to testosterone leads to decrease of sperm quality and changes in testis tissue in male rats, after puberty.

Cysteine proteinases (CPs) of Leishmania are considered to be attractive vaccine candidate in which their immunogenicity and immuno-modulatory effects have been confirmed. We have previously reported that a cocktail of two DNA plasmids encoding Leishmania major cysteine proteinases type I (CPB) and type II (CPA) induces a partial protective response in murine model of cutaneous leishmaniasis. The results also showed that the induced protective response was better than the responses given by each one the plasmids alone. However, in view of the capability of DNA plasmid for encoding several antigens, we investigated the possibility of using a single bivalent DNA vaccine, based on CP genes as an alternative mean of inducing protective immunity. Here we present evidence favoring that CPA and CPB delivered in the same plasmid DNA backbone either in separate locus or as a tandem fused gene induce partial protection against Leishmania major infection in susceptible BALB/c mice. Immunization of mice with these constructs promoted specific T-cell response of Th1 phenotype that is characterized by an increase in production of IFN-?. Our results confirm the previous observation about the possibility of DNA immunization against leishmaniasis using CP genes and lend support to the idea of using a single polyvalent plasmid DNA construct to elicit immune responses to several distinct antigens.