Tehran University Medical Journal

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Differentiated cells can change to embryonic stem cells by reprograming. Generation of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative and personalized medicine. iPSCs can self-renew and differentiate into many cell types. iPSC cells offer a potentially unlimited source for targeted differentiation. Through the expression of a set of transcription factors, iPSCs can be generated from different kinds of embryonic and adult cells. This technology for the first time enabled the researchers to take differentiated cells from an individual, and convert them to another cell type of interest, which is particularly to that person. When the set of master transcription factors containing OCT4, SOX2, KLF4, and MYC is expressed ectopically in somatic cells, the transcriptional network is propelled to organize itself in such a way as to maintenance a pluripotent state. Since iPSCs are similar to Embryonic Stem Cell (ESC), they can be considered as sources for modeling different diseases. iPSCs which are induced from somatic cells of patient can be useful for screening and drugs selection, and also introduce treatment via grafting the cells. Although this technology has been successful in different fields, the tumorigenesis of viral vectors during induction of reprogramming is a major challenge. Nevertheless, iPSCs are valuable for clinical applications and research. By discovery of these cells many challenges related to the safety, efficacy, and bioethics of ESCs are solved. Pluripotency is defined in two aspect of functional and molecular, by which functional regards the capacity of cell is generate three kinds of embryonic layers and germ line, and molecular aspect regards the identifying of molecules and genes that support functional features. Identification of these genes has been placed at the center of fields related to development and stem cell research. In this review, we discuss the process of generation of these cells, as well as required genes and factors for pluripotency, and also current progress in generation of iPSCs utilizing tens of reliable and new studies.

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Embryonic stem cells are pluripotent stem cells which have the ability to indefinitely self-renew and differentiate into all differentiated cells of the body. Regarding their two main properties (unlimited self-renewal and multi-lineage differentiation), these cells have various biomedical applications in basic research and cell based therapy. Because the transplantation of differentiated cells that are derived from embryonic stem cells is allogenic, they face the problem of immune rejection following the transplantation of embryonic stem cell-derived cells into patients. In 2006, researchers from Japan reported the derivation of a new type of pluripotent stem cells which could overcome the problem of immune rejection that is associated with the application of embryonic stem cells. They designated these cells as induced pluripotent stem (iPS) cells, because their production was ‘induced’ from differentiated somatic cells using a combination of four embryonic stem cell-associated transcription factors. Importantly, these pluripotent stem cells exhibit all the key features of embryonic stem cells including unlimited self-renewal and multi-lineage differentiation potential, and can pass the most stringent test of pluripotency which is known as the tetraploid (4n) complementation. Hence, in addition to bypassing the problem of immune rejection, iPS cells have all of the potential applications of embryonic stem cells, including in developmental studies, toxicology research, drug discovery and disease modeling. Also, considering that they could be generated from patient’s own cells, iPS cells hold great promise in the future of patient-specific cell replacement therapies using pluripotent stem cells. In this review article, we will present a comprehensive review on the how and why of the generation of iPS cell from somatic cells of the body and discuss how they should be characterized in terms of morphologically, pluripotent stem cell behavior, and the molecular signature. In addition, their medical applications as well as some of the considerations and future challenges in their use will be discussed.

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Helicobacter pylori (H. pylori) is the causative agent in development of gastroduode-nal diseases, such as chronic atrophic gastritis, peptic ulcers, mucosa associated lym-phoid tissue (MALT) lymphoma, and gastric cancer. H. pylori has been associated with inflammation in cardia, showing the fact that infection with this bacterium could also be a risk factor for gastric cardia cancer. Gastric cancer is the fourth most common cancer worldwide. This is the second leading cause of cancer-related deaths, and ap-proximately 700,000 people succumb each year to gastric adenocarcinoma. It has been estimated that 69% of the Iranian population currently harbor H. pylori infection. The prevalence of duodenal ulcer and gastric cancer is high in Iranian populations. However, this has been largely influenced by geographic and/or ethnic origin. Epidemi-ology studies have shown that host, environmental, and bacterial factors determine the outcome of H. pylori infection. The bacterium contains allelic diversity and high genet-ic variability into core- and virulence-genes and that this diversity is geographically and ethnically structured. The genetic diversity within H. pylori is greater than within most other bacteria, and its diversity is more than 50-fold higher than that of human DNA. The maintenance of high diversification makes this bacterium to cope with particular challenges in individual hosts. It has been reported that the recombination contributed to the creation of new genes and gene family. Furthermore, the microevolution in cagA and vacA genes is a common event, leading to a change in the virulence phenotype. These factors contribute to the bacterial survival in acidic conditions in stomach and protect it from host immune system, causing tissue damage and clinical disease. In this review article, we discussed the correlation between H. pylori virulence factors and clin-ical outcomes, microevolution of H. pylori virulence genes in a single host, microevolu-tion of H. pylori during primary infection and progression of atrophic gastritis to ade-nocarcinoma, and H. pylori infection status in Iran. Finally, we put forward the hy-pothesis that if the pattern of nucleotide sequence evolution shifts from recombination (r) to mutation (m) and the r/m ratio is reduced, bacterial pathogenicity may be re-duced while maintaining the bacterial life. However, this hypothesis should be further studied with future experiments.

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Background: Uterine myomas are benign tumors of the uterus and the most common solid pelvic tumors causing symptoms in approximately 25% of women in their reproductive years. However, its etiology and pathogenesis remain obscure there is increasing evidence that endometriosis is inherited as a complex genetic trait. Recent studies indicated the involvement of glutathione S-transferase M1 (GSTM1) gene in the pathogenesis of this disease and current investigations are devoted to the other members of phase II detoxification system genes such as glutathione S-transferase T1 (GSTT1). Therefore, current study was carried out to investigate the distribution of GSTM1 and GSTT1polymorphisms in Iranian population in order to estimate possible impact of null-alleles of each gene in development of this disease. Methods: In this study, 50 patients with endometriosis diagnosed by both pathology and laparoscopic findings according to the revised American Fertility Society classification of endometriosis were recruited from subjects referred to the Pasteur Institute of Iran between November 2012 to September 2013. Accordingly, controls (n=50) were subjects without any of aforementioned gynecologic conditions. The genomic DNA was extracted from peripheral blood leucocytes using the salting out method and GSTM1 and GSTT1 genotyping for gene deletions were carried out using Gap-polymerase chain re-action. Logistic regression analysis was applied to assess whether there was any significant risk increase between the case group with higher null genotypes compared to control group. The level of statistical significance was set at 0.05 and all analyses were conducted using the SPSS version 18.0 (SPSS Inc., Chicago, IL). Results: There was significant evidence that the distribution of the GSTM1 and GSTT1 genotypes differed between the patients and the controls with an allelic odds ratio (OR) of 3.56 (95%CI: 1.35-9.37, P=0.01) and 3.92 (95%CI: 1.4-10 P=0.009) respectively. Data analysis also revealed that individuals with both GSTM1 and GSTT1 null genotypes (-/-) had higher risk to develop the disease in comparison to the people with the both present (+/+) genotype (OR:19.23, P=0.007). Conclusion: The findings suggest that the GSTM1 and GSTT1 genetic polymorphisms are associated with the development of endometriosis in Iranian women which is in agreement with previous results obtained in other populations. However, the ethnic variations of polymorphisms should be evaluated in detail and differences should be incorporated into investigations of susceptibility variants for this disease.

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Eyes and the vision system allow the human being to receive information from the environment to the extent that 90% of the man’s information is acquired through observation, thus health and correct function of this organ have always been important. Diseases threatening vision such as Acute Macular Degeneration and Diabetic Retinopathy deprive millions of people of seeing every year while access to proper cures can prevent many ocular damages. Despite scientific progress in the medical fields over the recent decades there still exist many challenges in the field of ophthalmology and ocular diseases. As for ocular treatments, major challenges stem from pharmaceutical weaknesses, in other words in spite of access to the suitable drugs for ocular complications we have not yet succeeded to achieve an appropriate method to apply these drugs. By appropriate application of drugs we may deliver the active pharmaceutical ingredient to the target organ with the least side-effect, the most benefit and the highest level of patient compliance. Incapability of effective delivery of drug to the eye arises from the special physiology and anatomy of this organ. The static barriers such as Blood-Aqueous and Blood-Retinal and dynamic barriers such as conjunctival blood circulation and lymphatic clearance will reduce the bioavailability of ocular drugs. Overcoming the above-mentioned weaknesses requires a complete knowledge of the eye characteristics as well as acquaintance with novel drug delivery system. When speaking of drug delivery system (DDS) it means employing a two-part structure consist of active pharmaceutical ingredient (API) and carrier that in fact characteristics of formulated DDS will determine by the carrier. We may hope that by applying and designing modern pharmaceutical systems that mainly take advantage of nanoparticles we would be able to overcome many challenges of ocular drug delivery. The present study is aimed at reviewing the eye structure, challenges faced by ocular drug delivery, familiarity with nanotechnology and approaches of this science in the area of ophthalmology as well as mechanisms of designing a local system for effective drug delivery to the eye tissue.

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Growing and developing are influenced by genetic, social and environmental factors and it's most important and initial phase step is formed of the early life of the fetus and infant. According to the world health organization, the incidence of preterm birth and low birth weight are increasing in most countries that most of it related to developing countries. Low birth weight (LBW) and preterm birth are one the most important causes of death in the world and therefore are considered as one of the major health problems that can affect growing and developing so that it can threaten public health. Advances in medical technology in recent decades at intensive care unit, increased survival of premature infants and high-risk specialist care is needed, but failed, to reduce the complications of premature birth but it couldn’t reduce complications of preterm birth. There is also an increased recognition of the potential disconnect between perinatal outcomes and long-term outcomes. The administration of oxygen and postnatal steroids are prime examples of interventions that may have immediate positive effects but negative long-term effects. Many premature babies will be encounter with mobility problems, cognitive, neurosensory impairments, cerebral palsy, cognitive and language delays, neuromotor developmental delay, blindness and hearing loss, behavioral and psychosocial disorders, learning difficulties and dysfunction in scholastic performances in the future. These disadvantages appear to persist into adulthood and therefore have broad implications for society. Without a doubt, one of the tragedies of the world is people with physical or mental damage caused by premature birth, many of these disorders are not early diagnosed and the prediction of long term complications of infants discharged from the NICU is difficult. Although nourodevelopmental follow-up of these babies is a necessary part of the neonatal assessment but there is no standard process for it. The present review article aims to introduce the care process and tools that is used for following-up these babies, also introduces the application of screening tools for neuro-developmental care.

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In situ hybridization (ISH) is a method that uses labeled complementary single strand DNA or RNA to localize specific DNA or RNA sequences in an intact cell or in a fixed tissue section. The main steps of ISH consist of: probe selection, tissue or sample preparation, pre-hybridization treatment, hybridization and washing, detection and control procedure. Probe selection is one of the important aspects of successful hybridization. ISH sensitivity and specificity can be influenced by: probe construct, efficiency of labeling, percentage of GC, probe length and signal detection systems. Different methods such as nick translation, random priming, end tailing and T4 DNA polymerase replacement are used for probe generation. Both radioactive and non-radioactive labels can be used in order to probe labeling. Nucleic acid maintenance in samples, prevention of morphological changes of samples and probe penetration into tissue section are the main aims of sample preparation step. Then, a small amount of solution containing probe, is added on slides containing tissue sections for hybridization process, then slides are incubated overnight. Next day, washes are carried out to remove the probes which are not bound to target DNA or RNA. Finally, in order to be sure that the observed labeling is specific to the target sequence, using several control procedures is very important. Various techniques based on ISH consist of: Fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), genomic in situ hybridization (GISH), comparative genomic hybridization (CGH), spectral karyotyping (SKY) and multiplex fluorescence in situ hybridization (MFISH). One of the most common techniques of ISH is fluorescence in situ hybridization. FISH can be used to: 1) detect small deletions and duplications that are not visible using microscope analysis, 2) detect how many chromosomes of a certain type are present in each cell and 3) confirm rearrangements that are suspected after microscope analysis. In this technique different fluorescent labels are attached to the probes. In this review article ISH, its different types, their application, advantages and disadvantages have been considered.

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Cancer/Testis antigens (CTAs) as a group of tumor antigens are the novel subjects for developing cancer vaccine and immunotherapy approaches. They aberrantly express in tumors with highest normal expression in testis, and limited or no expression in normal tissues. There are important similarities between the processes of germ-cell and cancer cell development Spermatogenesis begins at puberty when expression of novel cell-surface antigens occurs when the immune system has been refined the ability to distinguish self from non-self. Whereas macrophage and lymphocytes are commonly found within interstitial spaces of the testis, these antigen-presenting cells are rarely seen within the seminiferous tubules. These observations have led to the concept of the immune privileged site for testis. Localized normal expression of the CT genes in testis that makes them immunogenic for immune system, in one side, and their abnormal expression in different kinds of cancer cells, in the other side, has make them as promising target for developing cancer vaccines and new cancer therapeutics approaches. In malignancies, gene regulation is disrupted which results aberrant expression of CT antigen in a proportion of tumors of various types. For some CTAs, data support their fundamental role in tumorigenesis. Several authors believe it is not clear whether they have an essential role in tumorigenesis or they are by-products of chromatin variations in cancer. There is a growing list of CTAs within them advanced clinical trials are running by using some of them in cancers like lung cancer, malignant melanoma and neuroblastoma. In this review we discuss the gene TSGA10 as an example of CT genes. TSGA10 expresses in its highest levels in elongating spermatids and localized in the fibrous sheath of mature sperm. This gene is proposed as a serological biomarker in cutaneous lymphoma. Its abnormal expression has been reported in different cancers such as acute lymphoblastic leukemia, breast, brain, gastrointestinal and a range of other cancers either in mRNA or protein levels. It has an important role in angiogenesis in cancer tumors because of its effects in the gene hypoxia-inducible factor (HIF1). Absence or lack of TSGA10 expression has been reported in ascosporic infertile men.

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Fibronectin (FN) is one of the essential component of the extra cellular matrix and their important role is as regulator of cellular activities and also fibronectin is an important scaffold for maintaining tissue. Fibronectin conformational changes expose additional binding sites that participate in fibril formation and in conversion of fibrils into a stabilized, insoluble form. In fact fibronectin is a connected glycoprotein disulfide dimer with sedimentation coefficient of approximately S 13 and 440 kDa molecular mass which is exist in many extracellular matrix and plasma with concentration of approximately 300 µg/ml that during the regeneration body tissues acts in severely regulated stages until regenerate the damaged tissue. Fibronectin has domains for interacting with other extra cellular matrix proteins, cell surface receptors, glycosaminoglycans (GAGs), and other FN molecules. This combination of domains allows FNs to bind simultaneously to cells and to molecules within the surrounding matrix. Also fibronectin have binding sites for collagen/ gelatin, heparin, fibrinogen, and other molecules. In the present study important roles of fibronectin in development, regeneration especially in nerves system and important role of it in treatment of some diseases have been reviewed. Present study has reviewed 77 publications by using of PubMed, NCBI, Elsevier, EBSCO and Nature databases for describing the important roles of fibronectin in biological systems. Studies have shown that fibronectin has diverse roles such as: cellular adhesion, embryonic differentiation, assembly of extra cellular matrix, connecting and cell growth, transformation as well as cell migration that each of this roles depends to fibronectins action site. Considering the important role of fibronectin in attachment of cancer cells to basal lamina, spread neoplasm, tissue regeneration and formation of extra cellular matrix better identification the properties as well as physiological applications of fibronectin in tissues and bodies of animals can provide the better understanding of physiological mechanisms and pathophysiological effects of cells on each other, and also provides the new ways for treatment a variety of diseases.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, involves almost all organs such as skin, heart, kidneys and central nervous system. The disease is characterized by vascular and connective tissue inflammation in a recurring pattern of remission and flare. Although the exact pathophysiology of disease has not been fully understood yet, the fundamental defect in SLE is attributed to dysfunction of T lymphocytes in controlling of B-cell that leads to polyclonal activation of B lymphocytes and production a large quantity of autoantibodies against nuclear and cytoplasmic components. These autoantibodies can damage tissues either directly or as a result of immune complex deposits. Several factors are involved in pathogenesis of SLE which can be divided into three major groups, environmental factors, genetic components, and immunological disturbances. They could breakdown body tolerance towards endogenous antigens and cause abnormal immunologic response to the healthy tissue, resulting in tissue damage. SLE occurs more frequently in female than male. It seems that immunological factors have important role in SLE. Inflammation and vascular endothelium irregularities are a number of main pathologies seen in SLE. Cytokines are protein mediators that play an essential role as regulator of innate and adaptive immune response against microbial agents or self-antigens. Influences of cytokines in autoimmune diseases such as SLE are poorly understood. Studies in both experimental animal models of lupus and patients with SLE have revealed a number of cytokine pathways that are important in the disease process. These studies showed that overexpression of inflammatory cytokines increases the proliferation of auto reactive B-cells and results in higher production of autoantibodies. Among them, the role of B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), TNF-α, IFN-α, IL-6, IFN-γ, IL-23/IL-17, IL-10, IL-21 are prominent, which is associated with the generation of pathogenic autoantibodies and formation of immune complexes. In this paper, the role of cytokines and their encoding genes are described, while therapeutic applications are also briefly presented.

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The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to viral vaccine can be achieved by using adjuvant. The ability of biological molecular adjuvant such as cytokines, interlukines, and bacterial derivatives to improve the immunogenicity of vaccines as a novel strategy is under evaluation, however, and immune system regulator proteins have additional considerations.

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Thymoglobulin is a purified polyclonal immunoglobulin that has been used widely over the last decades in the prevention and treatment of rejection following renal transplantation. This immunoglobulin works against human thymocytes. Since thymoglobulin does not contain the nephrotoxic properties therefore it can be used in induction therapy especially in patients with higher risk of graft rejection such as patients who receive graft from cadavers. Recent research showed also its beneficial role in cross-match-positive transplantation, a role that is mediated through conjunction with inhibitors of terminal complement activation. This immunoglobulin has also been used for treatment of rejection following renal transplantation. Thymoglobulin can have various effects on various Immune system cells including T cells, B cells and also plasma cells. Thymoglobulin also affects the Tcell surface antigens, natural killer-cell antigens, B cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors. Diverse effects of thymoglobulin on the immune system includes: T cell depletion, induce apoptosis in B cell lineage and interference with dendritic cell functional properties. Thymoglobulin can cause acute complications, delayed complications as well as infectious complications. Acute reaction events includes: anaphylaxis, fever, chills, dyspnea, nausea, vomiting and diarrhea. Thymoglobulin also induces cytokine release syndrome manifested by high grade fevers and chills and treated by steroid therapy. Delayed reactions events usually present as serum sickness and infections. Infectious complications are more important and include cytomegalovirus (CMV) infection, sepsis, candidiasis, herpes simplex and urinary infections. Thymoglobulin can also induce cytokine release syndrome. It has been thought that thymoglobulin increases the risk of post-transplant lymphoproliferative disorder (PTLD), however, debate still exists whether such an association is present when lower dosing regimens are used. In this review, we aimed to present first a brief history of thymoglobulin development and its mechanism of action and then assess the most recent published data regarding the role of thymoglobulin in following issues: immunological tolerance, ischemia-reperfusion injury, delayed graft function, prevention and treatment of acute allograft rejection, live donor transplantation, graft and patient survival and posttrans-plant lymphoproliferative disorder. This review can help specialist in transplant domain to appropriately used thymoglobulin in transplant patients.

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Despite the valuable results achieved in identification of genes and genetic changes associated with type 2 diabetes (T2D), lack of consistency and reproducibility of these results in different populations is one of the challenges lie ahead in introduction of T2D candidate genes. Therefore, the present review article aimed to provide an overview of the most important genes and genetic variations associated with development of T2D based on a systematic search in well-known genetic databases. For this purpose, the National Center for Biotechnology Information, Database of Genotypes and Phenotypes (NCBI dbGaP) and Human Genome Epidemiology Network (HuGENet) database were searched to find the most important genes associated with T2D. In addition, a gray literature search was conducted to collect any available information released by laboratories offering genetic tests such as deCODE genetics and 23andMe. Candidate genes were selected among the results of all databases based on the highest level of similarity. Subsequently, without any time restriction, PubMed, Scopus and Google scholar databases were searched using relevant Medical Subject Headings (MeSH) terms to access related articles. The relevant articles were screened to make a conclusion about the genes and genetic variations associated with T2D. The results revealed that four selected candidate genes, in order of importance, were TCF7L2, CDKAL1, KCNJ11, and FTO. The most significant single nucleotide polymorphism (SNP) associated with T2D in the TCF7L2 gene was rs7903146 however, the results showed a wide range of variation from slight association in the Amish (P= 5.0×10^-2) to strong association in European descent populations (P= 2.0×10^-51). Then, rs10440833 mapping to the intronic region of the CDKAL1 gene showed significant association with T2D (P= 2.0×10^-22). In the KCNJ11 gene, a missense variation (rs5215) in exon one was found to have the highest association with T2D compared with other SNPs discovered in this gene (P= 5.0×10^-11). Finally, rs8050136 located in the first intron of the FTO gene had the strongest association with T2D (P= 2.0×10^-17). On the basis of these results, it can be concluded that the current study can be introduced as a model for achieving well-documented results among spectrum of information available in genetic databases based on a systematic search strategy. The candidate genes and genetic variations presented in this review article might be applied for early diagnosis, prevention, and treatment of T2D.

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HIV/AIDS is among the leading causes of morbidity and mortality in world. There are more than 35 million people living with HIV/AIDS in the world. Although the annual incidence of HIV infection is decreasing globally, HIV prevalence is rising due to development of more effective treatment and higher survival. Iran suffers from concentrated HIV epidemics among injecting and non-injecting drug users. There are more than 27 thousand registered cases of HIV infection and it is estimated that there are above seventy eight thousand cases in the country. Regarding the burden of disease, it is projected that HIV/AIDS will have the highest growth during the next 10 years. The outcome of this epidemics will be determined by human behavior. HIV, psychiatric disorders and substance use disorders are closely correlated and are accompanied by similar risk factors. They also share common consequences such as stigma and discrimination. Correlation of psychiatric disorders, as one of the most influential determinants of our behavior, and HIV/AIDS infection is reviewed in this narrative article. Psychiatric disorders are associated with greater risk of HIV acquisition. Substance use disorders, both injecting and non-injecting, as well as severe mental illnesses put the individual at higher risk of acquiring HIV infection. Impaired judgment, diminished inhibition and control over behaviors, lack of insight and poor self-care have been proposed as the underlying mechanisms. On the other hand, HIV infection may put the individual at greater risk of developing a mental illness. Coping with a chronic and life-threatening illness, fear of stigma and discrimination, CNS invasion of the virus as well as the adverse neuropsychiatric side effects of anti-retroviral medications may all contribute to establishment of a psychiatric disorder. Although there exists a bi-directional correlation between mental health problems and HIV/AIDS infection, this reciprocity goes beyond. Psychiatric disorders can affect the patient’s adherence, access to treatment and care and can worsen the course and clinical outcome of the infection. The clinical importance, underlying mechanism and other implications of this correlation are reviewed in this article.

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Angiogenesis, as the process of new vessel formation from pre-existing vessels is dependent on a delicate equilibrium between endogenous angiogenic and antiangiogenic factors. However, under pathological conditions, this tight regulation becomes lost which can result in the formation of the different diseases such as cancer. Angiogenesis is a complex process that includes many gene products that are produced by different cells. Each of the processes influenced by specific genes that their expression can be regulated by hypoxi inducible factor-1 (HIF-1). Hypoxia, the imbalance between the oxygen in need and the oxygen available, usually occurs in tumors and ischemic cardiovascular diseases. In order to overcome this challenge, tumors regulate and control the expression of genes related to angiogenesis, cell cycle and metabolism using hypoxia-inducible factor 1 (HIF-1). HIF-1 was first recognized as a transcription factor involved in hypoxia-induced erythropoietin expression. As angiogenesis pathway molecules are being described, this factor has been characterized as a key transcription regulator for these molecules. In this review article, after discussing HIF-1 structure and characterization, the role of this important factor in angiogenesis and cancer as a pathological case and finally, the clinical applications has been evaluated. Articles related to the key words of hypoxia, HIF-1 and angiogenesis were searched from valid databases such as Springer Link, google scholar, Pubmed and Sciencedirect. Then, the articles related to the role of hypoxia and HIF-1 in activation of genes that are involved in angiogenesis and cancer were searched and selected for this study. Studies show that, HIF-1 activation of genes including vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), etc., induced angiogenesis in the tumor cells. Furthermore, the activation of genes such as insulin-like growth factor 2 (IGF2), transforming growth factor α (TGF-α) and MAPK and PI3K signaling pathway will also enable the survival and proliferation of tumor cells. HIF-1 by activating genes involved in angiogenesis and also activates signaling pathways associated with cell survival and proliferation plays an important role in the stability and growth of tumors. Therefore, better understanding of molecular mechanisms associated with this factor can be effective in the treatment of cancer.

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Viruses are important causes of acute and chronic diseases in humans. Newer viruses are still being discovered. Apart from frequently causing infections in the general community, many types of viruses are significant nosocomial pathogens that with emerging viruses has become a real issue in medical field. There are specific treatments, vaccine and physical barrier to fight some of these infections. Health care-associated viral infections are an important source of patient’s morbidity and mortality. The method of sterilization or disinfection depends on the intended use of the medical devices (comprising critical, semicritical and noncritical items) and failure to perform proper sterilization or disinfection of these items may leads to introduction of viruses, resulting in infection. Disinfection is an essential way in reducing or disruption of transmission of viruses by environmental surfaces, instruments and hands which achieves by chemical disinfectants and antiseptics, respectively. This review discusses about chemical agents with virocids properties (e.g. alcohols, chlorine compounds, formaldehyde, phenolic compounds, glutaraldehyde, ortho-phthaldehyde, hydrogen peroxide, peracetic acid, iodophor, ammonium compounds quaternary, bigunides and so on.), mechanisms of action and their applications in health care-associated viral infection control. As well as, we described an overview for hierarchy of viruses in challenge with disinfantans, effective agents on viral inactivation, i.e.targect viruses, viral stability or survival duration time in enviromental surfaces and hands. We explained disinfection of surfaces, challenges in emerging viral pathogens inactivation, viral resistance to chemical disinfectants and antiseptics. Because, there are laboratory studies and clinical evidences for some viruses which viral resistance to biocide or failure to perform proper disinfection can lead to infection outbreaks. Also, we described virucidal properties of antiseptics and introduced selected antiseptics with extensive virucidal action, because hands play an important role in the spread of many viral diseases, and regular proper hands hygiene is essential to decontaminate hands and can interrupt the spread of viruses. Here, we compared the currently available laboratory methods, standard methods from many countries and kinds of viruses in these methods for evaluation of virocide activity. Finally, it’s good to know: any disinfectant is not virocide unless it confirms by laboratory methods.

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Primary ovarian insufficiency (POI), commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%). The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH). There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and timing of fertility preservation by giving an estimated window of fertility. The objectives of the current review are to report on the etiology of POF induced through cancer therapy.

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Stem cells are undifferentiated and multi pluripotent cells which can differentiate into a variety of mature cells and tissues such as nervous tissue, muscle tissue, epithelial tissue, skeletal tissue and etc. Stem cells from all different source have three unique features: 1) Proliferative capability: Stem cells are capable of self dividing and self renewing for long periods or more than six months at least that called immortalization. 2) Undifferentiated nature: It’s considered as one of the essential characteristics of stem cell, so it doesn't have any tissue-specific construction. 3) Differentiation to the different cells from all organs: This ability can Induced by tissue specific transcription factors. Because of that, they are so important in prevention and treatment of human disease. Depending on the sources from which they derive, they have different types which can be used to produce special cells and tissues. The most significant types of stem cells are; embryonic stem cells (ESCs) which are derived from embryos, adult stem cells (ASCs) which are derived from differentiated cells in a specific tissue, induced pluripotent stem cells (iPSs) which are produced from adult differentiated cells that have been genetically reprogrammed to act resemble to an embryonic stem cell and cord blood stem cells which contains haematopoietic stem cells and derived from the umbilical cord after gestation. By providing a medium containing of special growth factor, it is possible to orientated stem cell differentiation pathway and gained certain cells from them. The important uses of stem cells includes damaged heart tissue cells improvements and bone tissue repairing, cancer treatment, damaged neurological and spinal tissue repairing, improving burns and injuries and the treatment of diabetes, infertility and spermatogenesis dysfunction. Furthermore, the application of them in gene therapy is an important issue in the modern medicine science due to the role of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

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Hemoglobinopathies are most common inherited disorders in the world; approximately 7 percent of the worldwide population and 5-6 percent of population of Iran are carriers. The hemoglobin disorders inherit as autosomal recessive and are very common in the Mediterranean area and much of the Asia and Africa. The control of this inherited disorders need to genetic counseling and accurate screening by more advanced and more accurate methods. This study explains features of current Iran hemoglobin disorders, nominates the accessible methods for screening them and introduces the capillary zone electrophoresis as a rapid and more accurate method. The required data were extracted of various articles and then for good explanation, current Iran hemoglobinopathies properties were showed in the tables and electropherograms of important hemoglobin disorders in Iran population were provided for help to interpretation results of blood tests by capillary zone electrophoresis method. Hemoglobin disorders are including thalassemias and hemoglobin variants; Disruption in the production and malfunction of globin chains cause types of hemoglobin disorders. We cannot introduce one of clinical laboratory tests as critical and basic method for screening and distinguishing types of inherited hemoglobin disorders as alone. For distinguishing the types of them must be prepared enough information and data of the hemoglobin disorders and for more accurate analysis must be used simultaneously different methods as gel electrophoresis, high performance liquid chromatography, isoelectric focusing, capillary zone electrophoresis or molecular tests. The capillary electrophoresis is an accurate and rapid method for screening types of the hemoglobin disorders. Other side this method cannot analyze all of them, so must be used biochemical, biophysical and molecular methods for confirmation the results. This review showed we can use the capillary electrophoresis and HPLC as two complementary methods for hemoglobinopathies screening. We can analyze by the methods more hemoglobin disorders and decrease more laboratory errors. Moreover, we must have patient history, hematological indices, information and data of types of hemoglobinopathies. The patient history and complete blood count results as red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration can be useful and helpful in screening the hemoglobin disorders and then distinguishing all of hemoglobin disorders.

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It was assumed that the loss of cardiomyocytes is irreversible. The main goal is to develop widely available and clinically applicable treatments for heart diseases. The several studies have showed that the use of stem cells can improve complicacies such as cardiovascular diseases. Stem cells have a potential benefit of the self-renewal and cell differentiation into the cell types that can play an important role in the organogenesis and the embryonic development. In a lifetime, the heart muscle has a population of cardiac stem cells (CSCs) in which a dramatically increase after cardiovascular damages. So far, seven types of CSCs have been discovered with the different molecular phenotype and the cell differentiation potential. In this regard, the proliferation and the differentiation increase of CSCs in the cardiac ischemic areas can be a key factor to improve heart complicacies. Paracrine and/or autocrine factors, the extracellular matrix and the genetic mediators including microRNA can control the function of CSCs. It has clearly been understood that the factors mentioned previously have the ability to improve these complicacies. The differentiation, the survival and the self-renewal of CSCs are largely under the control of factors in the heart microenvironment. Several studies showed that the cytokines and the growth factors play the important role in the proliferation and the migration of CSCs. Taking advantage of these factors together CSCs to repair damaged heart can enhance this method efficiency. This review will discuss the different kinds of CSCs, their molecular phenotype and cardiac regeneration potential in order to improve cardiovascular diseases. It seems that CSCs-based therapy is emerging as a novel approach for myocardial repair over conventional cardiovascular therapies. Therefore, understanding the new aspects on the molecular mechanisms and the signaling pathways involving CSCs is critical for the development of the therapeutic strategies in cardiac patients that would be valuable for researchers in both fields of molecular and clinical cardiology.