Tehran University Medical Journal

Stem cells are undifferentiated biological cells that can differentiate into more specialized cells and divide (through mitosis) to produce more stem cells (self-renew). In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. Mesenchymal stem cells (MSCs) are multipotent cells that are called as one of the most adult stem cells. Due to their highly proliferative potential and their suitable self-renewal capacity, these cells have provided a powerful and promising source for use in the field of regenerative medicine. Also, mesenchymal stem cells are known for their important properties involving multilineage differentiation potential, trophic factor secretion and localization along various organs and tissues. So that MSCs can differentiate into a variety of cell lineages, including: Osteoblasts (bone cells), chondrocytes (cartilage cells), adipocytes (fat cells), myocytes (muscle cells), hepatocytes (liver cells) and endothelial cells. Efficacy of differentiated MSCs to regenerate cells in the injured tissues requires the ability to maintain the differentiation toward the desired cell fate. Since MSCs represent an attractive source for autologous transplantation, cellular and molecular signaling pathways and micro-environmental changes have been studied in order to understand the role of cytokines, chemokines, and transcription factors on the differentiation of MSCs. The differentiation of MSC into a mesenchymal lineage is genetically manipulated and promoted by specific transcription factors associated with a particular cell lineage. Recent studies have explored the integration of transcription factors, including Runx2, Sox9, PPARγ, MyoD, GATA4, and GATA6 in the differentiation of MSCs. Therefore, the overexpression of a single transcription factor in MSCs may promote trans-differentiation into specific cell lineage, which can be used for treatment of some diseases. In this review, we critically discussed and evaluated the role of transcription factors and related signaling pathways that affect the differentiation of MSCs toward adipocytes, chondrocytes, osteocytes, skeletal muscle cells, cardiomyocytes, and smooth muscle cells.
 

Sudden cardiac death in sport, although rare, but is a tragic event, attracting the media and public attention. Sport and exercise may act as a trigger for sudden cardiac death. Risk of sudden death in young athletes with cardiovascular disease is 2.5 times more frequent than non-athlete individuals. More than 90% of cases of sudden death occur during or immediately after training or competition. Incidence of sudden cardiac death in any population, including athletes, is related to multiple factors such as gender, age, race, nationality, diagnostic screening methods and preventive measures for sudden cardiac death. Otherwise, incidence rate of sudden cardiac death is linked to the used definition and method of diagnosis. Different cardiovascular disorders may result in death of young athletes and hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia and aortic rupture are among the most common causes. Marfan syndrome, dilated cardiomyopathy, viral myocarditis, Wolff-Parkinson-White (WPW) syndrome, congenital long QT syndrome, Brugada syndrome and commotio cordis are reported as other etiologies. In older athletes (more than 35 years), ischemic coronary heart disease is responsible for majority of the cases similar to the general population. Because the outcome of sudden cardiac arrest in sports is very poor except in few cases, proper national strategies are needed to diminish the burden of sudden death in young athletes. It seems that there are two main strategies to achieve this goal: A) Primary prevention with use of purposeful pre-participation evaluation programs. This evaluation should focuss on the proper history and physical examination. Nevertheless, there is significant debate between American and European countries regarding the use of paraclinical investigations (especially ECG). American heart association does not recommend ECG as an essential part of evaluation. In contrast, European society of cardiology and international olympic committee advocate ECG for all athletes younger than 35 years. However, all evaluations should be based on national, generally accepted standards and done by well-educated experts. B) Setting evidence-based and updated protocols for early and effective cardiopulmonary resuscitation (CPR), attendance of well equipped medical staff and early access to automated external defibrillator (AED) in all sport events and implementing CPR education in all coaching training courses.

Uterine sarcomas comprise a group of rare tumors with different tumor biology, natural history and response to treatment, contain just 3-7% of total uterine malignancies and about 1% of all gynecologic cancers. Although they cause important part of women death due gynecologic cancers. These tumors have aggressive behavior and high recurrence rate, even when confined to the uterine corpus at the time of diagnosis. The most common of uterine sarcomas is leiomyosarcoma. The incidence of leiomyosarcoma is increased after age 50. Traditionally, carcinosarcomas were named as Malignant Mixed Mullerian tumor (MMMT), but in recent classification according to their pathologic structure and its behavior, these tumors are classified as carcinomas. The rare group of sarcomas is endometrial stromal sarcoma (ESS), which occurres in younger women. In a medical studies search from 2000 to 2017, all kinds of uterine sarcomas, pathologic diagnostic methods, primary treatment and supportive treatment have been analyzed. Last histological classification is based on FIGO 2009 and WHO. According to such classification, sarcomas divided into three subtypes: leiomyosarcoma, endometrial stromal sarcoma and carcinosarcomas. Diagnosis of sarcoma before treatment and discrimination from benign myoma by current diagnostic methods is difficult. Preoperative endometrial sampling identifies only 25% of sarcomas. It may be the myometrial origin of tumor. Currently, MRI, ultrasound and PET scan may be used for the diagnosis of tumor. The gold standard of treatment is complete and intact resection of tumor considereing free margins. In advanced or recurrence disease, cytoreductive surgery followed by chemotherapy is the choice of treatment. If technically it is not possible or there are extra abdominal metastases, palliative chemotherapy should be considered. Combination of gemcitabine and docetaxel is an acceptable choice. Recent studies are going to approve the effective role for targeted agents with or without cytotoxic chemotherapy in these group of aggressive tumors. The only drug in this group has approval is pazopanib. However, it did not achieved acceptable responses in phase I, II studies. As regards of tumor biology and inappropriate response to chemotherapy and radiotherapy, sarcoma have poor prognosis in all stages.

The members of Mycobacterium tuberculosis complex (MTBC) known as causative agents of human tuberculosis. Tuberculosis infection is one of the most important occupational risks for healthcare workers (HCWs) in most countries, such as Iran. In general, there are two types of tuberculosis, they include: latent infection and active TB. Latent tuberculosis infection (LTBI) means: a patient is infected with Mycobacterium tuberculosis but, the patient does not have active tuberculosis, clinical symptoms and radiological findings. According to studies, TB infection from patients to health care workers, depending on geographic region and economic situation is two to five times more than general population. The lowest incidence and the highest rates of LTBI prevalence among HCWs were 7% in Mashhad and 82.8% in Zahedan respectively. The risk factor acquisition of TB infection was a significant relationship with certain hospital wards (lung disease unit, laboratory, etc.), Increasing age and duration of employment. And results of this study show that TB is a significant problem among HCWs in Iran. Infection control and personal protective measures with training programs to patients and HCW is required to reduce the occupational risk of TB. Early detection of Mycobacterium tuberculosis and prevention treatment in people with latent TB are key elements in control of tuberculosis. Until now, different methods for detection of latent tuberculosis infection has been introduced that are not gold standard none of them. However, the most important methods, tuberculin skin test and the tests that based on measuring the production of interferon gamma are recommended, but each one of them has advantages and disadvantages. However, in all the articles of the tuberculin skin test is used for screening and early diagnosis of latent tuberculosis infection. So, the aim of this study was to Incidence and prevalence of latent tuberculosis infection in health care workers and risk factors, advantages and disadvantages of each method for diagnosis of latent tuberculosis infection and evaluate different strategies for reducing the incidence of latent tuberculosis infection in health care workers.

Cancer is the major cause of death in the world and the rate of mortality is higher in developed countries. Therefore, lifestyle could be effective in promoting the cancer. The pancreatic tumors, are 8th cause of mortality due to cancer, which have several types, among them ductal adenocarcinoma is the most common and includes 85% of cases. Since, it is almost impossible to diagnosis the tumor in early stages of the disease, it contributes to high rates of mortality, although if it diagnosis in early stage and the surgery performed for them only 10-20% of patients will be survived. Metastasis occurs when the tumor is smaller than 2 cm in size and because the pancreas is located in the depth of abdomen, typically, it happens after tumor is spread to other organs. A combination of medical imaging, blood tests, and examination of tissue samples are usually made for diagnosis and based on the cancer stage, surgery, radiotherapy and chemotherapy are chosen as treatment options. Some rare genetic variations can cause pancreatic cancer and about 5-10% of cases are linked to inherited genes. However, major risk factors are including age, obesity, tobacco smoking and diabetes. Smoking counts for about 25% of cases, and the diabetes is the main symptoms of pancreatic cancer, which observed in about 80% of cases. But, it is still unclear whether diabetes is a predisposing factor in pancreatic cancer, or the outcome of tumor progression. Recent studies have shown that, diabetes is unique in pancreatic cancer which is not related to common types. Currently, CA 19-9 is the only reliable tumor marker for pancreatic cancer that its frequency also increases in non-bad conditions, such as pancreatitis and obstructive jaundice, so is not sensitive and specific enough for diagnosis of this cancer. Due to researches continue to find more specific markers. In this review the etiology of pancreatic cancer, diabetes associated with this type of cancer and significant biomarkers for diagnosis will be considered.

Before the recent outbreaks of Zika virus, few people have ever heard of its name. Even virologists had paid little attention to this member of the Flaviviridae family. Hence, up to January 2016, only 269 articles about Zika virus had been indexed in PubMed compared to the 9187 articles related to dengue virus. However, declaration of the World health organization (WHO) about the global Zika virus spreading, which has been associated with birth defects and some neurological problems, diverted more attention to this forgotten virus. Afterwards, the virus hit the headlines and became a research interest. Since then, up to 9 August 2017, the number of Zika related articles indexed in PubMed reached to 3214. Zika virus is a re-emerging arbovirus. The First detection of Zika virus was in Uganda in 1947. It belongs to the Flavivirus genus in the Flaviviridae family. Zika can typically cause a mild and self-limiting disease in a healthy person. However, in pregnant women, it might cause birth defects and occasionally it can be associated with peripheral neuropathy such as Guillain-Barre syndrome. Although many research have been conducted to find out the casual link between this virus and these disorders but this relationship is still dim and controversial. Considering its recent epidemics in 2015 and 2016 the geographical distribution of Zika virus seems to expand all over the world progressively. Interaction between virus and vector is dynamic. Variety of competent vectors and adaptability of virus to new arthropod vectors are the two major factors for this process. According to the last report published by WHO, 84 countries/territories in five continents have reported the circulation of Zika virus in their area. In the recent outbreak, WHO regional office in our region (EMRO) have reported no case of Zika virus transmission from this region. Nonetheless, because specific and competent vectors exist in some countries, this region has a potential of epidemic risk. Until now we have neither autochthonous nor imported case of Zika virus in our country but we should prepare for any unexpected situation. In this review, we will discuss new findings about the history, virological features, vectors, transmission routes and epidemiological aspects as well as laboratory diagnosis of Zika virus. In addition, the epidemiology of this virus in Iran will be discussed.

Thyroid cancer is one of the most common endocrine malignancies and in the last two decades the number of involved people in the world has been increased. Thyroid cancer in Iran is the seventh most common cancer in women and 14th in men. In recent years many achievements regarding to molecular pathogenic factors such as the substantial role of signaling pathways and molecular abnormalities have been made. Nowadays there is no efficient treatment for progressed thyroid cancer that does not respond to radioiodine therapy which are included poorly differentiated, anaplastic and metastatic or recurrent differentiated thyroid cancer. Although the results of some clinical trials in phase II for treatment of progressed thyroid cancer are rewarding but none of the treated patients responded to treatment and only a few of them responded partially to the treatment which indicates that the treatment can only control the condition of patients with advanced disease, therefore it is needed to consider other alternative solutions which would be helpful in controlling the disease. Epigenetic is referred to study of heritable changes in gene expression without changes in primary DNA sequence. The main mechanisms of genetic and epigenetic alterations are including mutations, increasing the gene copy number and aberrant gene methylation. Epigenetic defects are prevalent in different types of cancers. Aberrant methylation of genes that control cell proliferation and invasion (p16INK4A, RASSF1A, PTEN, Rap1GAP, TIMP3, DAPK, RARβ2, E-cadherin, and CITED1), as well as specific genes involved in differentiation of thyroid cancer (Na+/I- symport, TSH receptor, pendrin, SL5A8, and TTF-1) in association with genetic alterations, leads to tumor progression. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression or function. Many of these molecular changes can be used as molecular markers for prognosis, diagnosis and new therapeutic targets for thyroid cancer. This article is about the most common genetic and epigenetic alterations in thyroid cancer which can be complementary together in recognition of new treatments for the disease.

Infertility influences an estimated 20% of couples worldwide. The factors that can affect the fertility potential are equally distributed between men and women. Despite extensive research in male infertility, the etiology in majority of infertile men is unknown. In 2010, there was an opinion published in Nature asking a selection of leading researchers and policy-makers about what their future focuses will be in 2020. Metabolomics was mentioned as the leading omics technology by them. The word metabolomics has been defined almost 20 years ago. However, the clinical metabolomics history goes back to more than 1,000 years ago. The great Persian physician and philosopher Avicenna observed an individual urine changes during illness. Today, the color or smell changes are known to be caused by metabolites deregulation indicating metabolic diseases. Metabolomics approach is a systematic analysis of the unique pattern followed by a specific biochemical pathway that uses a biological material, e.g. spermatozoa or human seminal plasma. For the diagnosis of infertile men, the typical parameters of semen analysis are: sperm motility, sperm morphology, concentration and count. Human seminal plasma is a valuable biological source which was not used in the diagnosis of infertile men, unfortunately. To the best of our knowledge, there is no parameter for analysis of the human seminal plasma. Thus, the need for a novel parameter to diagnose infertile men is urgently needed. We recommend the use of seminal plasma in order to diagnose infertile men according to our previous research. Only a handful studies have used metabolomics approaches in the male infertility. In this study, we summarize the current research and our contribution to the field of male infertility and metabolomics. One of our main contributions has been to use metabolic profiling of seminal plasma from non-obstructive azoospermia to find 36 potentials biomarkers for detection of spermatogenesis. A search in the PubMed using keywords “metabolomics” and “infertility” shows only 59 publications. This demonstrates how newborn the metabolomics in its application for male infertility is. In this review article we have tried to have a comprehensive and specific approach to male infertility from a metabolomics perspective and related techniques.

Cancer/testis antigens (CTAs) are a kind of antigens that their expression mostly is restricted in testis and female’s genital organs. Tumor cells often express antigens whose expression is normally limited to germ cells. CTAs are composed of a vast gene family of closely related members and are commonly classified into two groups: the CT-X antigens that are encoded by the X chromosome and the non-X CTAs that are encoded by the autosomes. CTA are extensively and variably dispersed between tumors of diverse histotypes. CTA are broadly expressed in tumors, but not in normal tissue except for testis that is not available to the immune system, actually, the blood-testis barrier and the lack of HLA class I expression on the surface of germ cells avoid the immune system from the interaction with CTA proteins to be identified as non-self-structures. Consequently, CTA can be regarded as fundamentally tumor-specific targets. With extensive investigations on the function of this important biological molecules, their functions are somewhat revealed. Because of their high immunogenicity, tumor-limited, and biased expression, detection of these molecules provides unprecedented chances for further research and clinical development in the field of immunotherapy and cancer diagnosis. Also, growing evidence discloses that a number of CTAs stimulate epithelial mesenchymal transition (EMT) and generation of cancer stem-like cells, increasing metastasis, invasion and tumorigenesis. According to recent clinical attention, more features of CTA regulation are explored. CTA expression has been confirmed in a variety of human cancer tissues and some of them have been discovered to cause humoral and/or cellular immune responses in cancer patients, likewise, they displayed intertumor and intratumor heterogeneity in expression levels. CTAs are excellent targets for targeted tumor therapy, anticancer drug discovery, and diagnostic biomarkers, similarly, appreciated genes in the study of promoting tumorigenesis, immunotherapy, and malignant progression. This review summaries and classifies our current understanding of the complex and biased process of CTAs mRNA and protein expression in cancer, and provide the most current information on their function and regulation.
 

Immunotoxins such as pseudomonas exotoxin are Molecules with a unique structure like toxin-antibody part. These immunotoxins are two functional which crossing the cell membrane and enters the target cell and destroy the cell. Toxin-based treatments are a widespread research field and can have broad applications in the biology and public health. Immunotoxins act selectively against cancer cells and have a good potential for detecting and targeting cancer cells. Specific immunotoxins to target immune cells due to the selection type antibody and antibodies are responsible for the identification of the target cells. Cancer is becoming a major cause of death in most developed countries. In order to have a strong factor in cancer repression, that agent must target the cancer cells directly and specifically. Often, but not always, immunotoxins are produced for disabling and killing cancer cells, that this issue is one of new therapeutic approaches in recently. Clinical aims to designing and create new cancer therapies focused with this approach, a lot of information about the toxin and intracellular pathways have been obtained. So, toxins in medicine are useful for the treatment of human disease and study of professional cellular functions. So, immunotoxins have a high potential for cancer treatment. Other applications of immunotoxins, including immune system regulation and treatment of viral diseases and parasites diseases. More research is needed to improve the immunotoxin effects and to reduce their side effects. On the whole, with design creative, clever and experienced programs, many human diseases, particularly cancers can be in a short period of time and faster than other methods of treatment that the treatment of long, to be treated. Following the design and implementation of clinical trials, the effects of immunotoxins on animal tumorigenic models were performed. In fact, in this study, we focus on the use of protein-bound toxins with bacterial and herbal sources and more specifically Pseudomonas immunotoxins which attached to antibodies to target cancer cells.

Nowadays, there are various animal models of acute and chronic seizures. Some chemical and electrical models such as seizure induced by pentylenetetrazol injection and maximum electric shock has been developed over of six decades and different kinds of chemical, electrical and genetic models have been admitted up to now. Among chemical models of seizure induction penicillin, bicuculline, tetanus toxin, pentylenetetrazol, pilocarpine and kainic acid are the more common chemoconvulsants to induce acute and chronic seizures. Numerous mechanisms involved in different models lead to develop different types of seizures. This variety leads to be confused beginner researchers which model should be carried in a research hypothesis. This study was aimed to illustrate how choose the most proper animal model for a hypothesis as well as different animal models of seizure and epilepsy. Penicillin and bicuculine are most proper models to induce focal seizures. In addition, pilocarpine and kainic acid are able to develop temporal lobe seizures. Pentylenetetrazol and tetanus toxin could develop acute and chronic generalized and tonic-clonic seizures. Furthermore, maximum electric shock has been well known as a proper model for acute seizures induction. Electrical kindling of amygdala could develop repetitive temporal lobe seizures. Hypoxia model of seizure is more used for screening of anti-epileptic drugs, long-term consequences, and epileptogenesis mechanisms. Also, hyperthermic (febrile) models of seizure are reliable for studying epileptogenesis mechanisms and cognitive consequences. Genetic models such as recurrent simultaneous (such as GAERS, WAG/Rij) and reflex seizures (such as GEPR) are more valid in some studies, including absence and audiogenic seizures. WAG/Rij rats have been known as the most valid animal model for absence epilepsy. It should be noted that the animal model is a simple expression of a complex system and it covers only a part of what happens in humans’ body. The most important use of animal models of seizure is developing and finding more effective and new anti-epileptic drugs. Therefore, proper selection of the animal model between numerous animal models of seizure induction is crucial to design an equitable hypothesis. The evidences reviewed in this study made beginner researchers potent to choose the best model.

Depression is the psychological disorder which caused by chronic stress and extensive communication network between the gastrointestinal system via the “gut–brain-microbiota axis”. Depression can systematically activate/deactivate many genes and signaling molecules involved in the pathogenesis of the gastrointestinal disease. Whereas, most of the anti-depressant drugs suppress the depression symptoms by altering the neurotransmitters activity; studies on probiotics have shown the anti-depressant potential of them. Nutritional psychiatry is a field of psychiatry that investigates the relationship between dietary patterns and risk of mental disorders. The special type of probiotic has been identified to improve a number of diseases, such as diabetes, obesity, gastrointestinal infections, cancers, reduction of allergies and mood disorders such as depression. There is an evidence about therapeutic effects of probiotics in symptoms of depression, but because of the low number of samples, the limitation in use of different strains of bacteria and the limited laboratory equipment, it is difficult to make a definitive view about these results and need to more clinical study to determine the effective dose of probiotics in the treatment of depression. The articles related to this subject were collected from reliable database till the 2017 year, new studies and reviews articles which determine the effects of probiotics on the treatment of digestive and neurological diseases. The objective of this review is to study the current clinical research about the effects of probiotics in the treatment of symptoms of depression and discuss future directions in this field. Most of the studies demonstrated probiotics’ ability to improving mood, change behavior and improve the symptoms of stress and depression such as insomnia by increasing of serotonin and reducing of inflammation; and modulation of emotional behavior with effect on specific cytokines in brain. It has been discovered that probiotics have therapeutic effects extend beyond the gut and into the central nervous system by influence signaling pathways. In conclusion, it seems they have the potential to be used as a dietary supplement to optimize and enriched the food products and effective step in the prevention and treatment of various disorders in the nervous system instead of chemical drugs.

Today, nanoscience has grown and developed in various medical and therapeutic areas, including cancer treatment. On the other hand, cancer and its types have been rumored and inclusive and many people suffer from this fatal and deadly disease. Currently, existing therapeutic method, including chemotherapy, radiotherapy, and etc., along with the therapeutic effect, cause complications that are unpleasant for patients. Hence, scientists and researchers are looking to develop and improve treatment options and methods to deal with this serious disease. Today, nanoscience and nanotechnology have become widespread, and its various fields, including nanoparticles, are widely used for a variety of applications, especially for delivery of drugs and diagnostic items and imaging cases. Nanotechnology-based release systems have a significant impact on the release of cancer drugs. Advances in bio-materials and bio-engineering are contributing to new approaches to nanoparticles that may create a new way for the improvement of cancer patients. Nano-technology in the drug release system has had a great impact on the selection of cancer cells, the release of a targeted drug, and overcoming the limitations of conventional chemotherapy. At the present many drug delivery systems are now made of nanoparticles, and various substances have been used as drug-stimulating agents or as a reinforcing agent to improve the efficacy of the treatment and durability and stability and also the safety of anticancer drugs. The materials used to release cancer drugs are divided into various categories such as polymer, magnetic, biomolecules. In the meantime, polymer nanoparticles have been organized in the carriers of anti-cancer nanoparticles due to the process of easy production, biocompatibility, and biodegradability. Although the loading of hydrophilic compounds is still confronted with limitations, due to the diversity of nanoparticle structures, it is possible to encapsulate various molecules. Also, surface changes and modification such as binding to antibodies and target ligands can also be applied to these materials, to act as target drug delivery to increase the effectiveness of treatment process. In this article, we will have an overview of cancer disease and cancer drugs and also nanoparticles and their contribution to cancer treatment.

Cancer is one of the most dangerous health problems of today modern societies which has an increasing rate especially in developing countries. There are many diverse ongoing treatment attempts trying to defeat cancer. Despite that, scientists have been unable to find a permanent cure for this disease. In many cases although there is a successful first response in patients, cancer cells are finally able to withstand therapeutic procedures and even use chemo-resistance to take advantage of treatments to facilitate tumor growth, resulting in cancer remission. Therefore, and mostly in recent two decades, scientists have been trying to choose their treatments just as smart to be able to conquer cancer. One of the best methods of this smart defense is to target weak points of neoplastic cells and use them for designing drugs. In this case it would be most probable for cancer cells not to have a chance to confront and cause chemo-resistance. Total endeavors to fulfill this goal are named “targeted cancer therapy”. This therapeutic approach is mostly consisted of two different procedures: 1- designing and using specific drugs to target cancer cells’ mutated genes; which will be defined by checking the genetic background of tumor cells for each specific cancer type. EGFR, RAS, VEGF and HIF-1α are among the pathways that have already been used as targets. 2- The other procedure could be methods that would carry drugs directly to unhealthy cells to prevent further side effects for normal cells of patients. It would be possible by designing specific antibodies to target antigens of neoplastic cells. Ribonucleic sequences (miRNAs and siRNAs) are also very promising as new drugs and nanoparticles have enabled us to increase drug concentration in tumors. The ultimate goal of these new experiments is to suggest specific drugs for each patient based on the nature of one's disease and genetic background, which will bring about "personalized medicine" era. Using valid new references, this review article first presents targets that are currently being used for this targeted therapy, their logic of choice and the drugs that have already been produced for clinical trials. Smart methods of drug delivery are also presented and discussed afterwards.

The natural killer group 2D (NKG2D) is a transmembrane protein and a member of the CD94/NKG2 family of C-type lectin-like receptors. NKG2D is encoded by the KLRK1 gene, which is located in the NK-gene complex (NKC) placed on chromosomes 6 and 12 in mice and humans, respectively. NKG2D forms a homodimer structure and binds through ectodomains with its related ligands. Each of its monomers consists of two β-sheets, two α-helices, and four disulfide bands and also contains a β-strand that distinguishes it from other C-type lectin-like receptors. NKG2D ligands are homologs of major histocompatibility complex (MHC) class I molecules in mice and humans. MHC class I chain-related protein A (MICA) and B (MICB) and human cytomegalovirus UL16-binding proteins (ULBP1-6) are recognized by the human NKG2D. In Natural Killer (NK) cells, NKG2D-mediated cytotoxicity can be elicited via two different systems by signaling from immunoreceptor tyrosine-based activation motifs in DAP12 or via a Syk-independent pathway activated by DAP10. Therefore, NKG2D is an activating immunoreceptor which was first recognized on NK cells but subsequently found on γδT cells, CD8+ αβT cells, and macrophages. NKG2D-ligand diversity may facilitate the detection of the presence of a broad range of viruses and may provide protection against rapidly evolving cancers. NKG2D ligand recognition induces and/or improves immune responses to cancer cells. NK cells recognize a wide range of stressed cells. The activation of NKG2D receptor can lead to the lysis of the target cell and the production of various cytokines and chemokines depending on the nature of the stimulation as a result of NK and myeloid-mediated innate immunity and as well as T γδ and CD8+ mediated-adaptive immune system. However, inappropriate expression of NKG2D ligands could cause autoimmune diseases in healthy cells, including rheumatoid arthritis, colitis, celiac disease, multiple sclerosis, alopecia areata, type 1 diabetes, and chronic obstructive pulmonary disease. Therefore, a precise understanding of the structure and function of NKG2D receptor and its interaction with various ligands may lead to the development of strategies to treat autoimmune diseases. Hence, the purpose of this review is to examine the detailed studies on the function of NKG2D receptor and their related ligands.

The cartilage is a connective tissue that, due to the strength of its extracellular matrix, allows the tissue to tolerate mechanical stress without undergoing permanent deformation. It is responsible for the support of soft tissues and due to its smooth surface and elasticity, gives the joints the ability to slip and bend. excessive weight, excessive activity, or trauma can all cause cartilage to injury. The injury can lead to swelling, pain and varying degrees of mobility loss. The process of repairing musculoskeletal (orthopedic) injuries has led to problems in the medical field, which can be attributed to the inherent weakness of adult cartilage tissue. Therefore, this necessitates research focused on the development of a new restructuring strategy by combining chondrocytes or stem cells with scaffolds and growth factors to address these problems. Correspondingly, the recent tissue engineering strategies strongly support the simultaneous use of stem cells, scaffolds and growth factors. It has also been observed that due to the relatively low proliferation of transplanted chondrocytes, new cartilage models construction have examined the use of adipose-derived stem cells. Mature adipose tissue is produced as an important source of multi-functional stem cells that can be easily separated from the stromal vascular fraction (SVF) by adipose liposuction digestion. The adipose-derived stem cells are easily accessible without any serious complications and have the power to differentiate into several cell lines, including chondrocytes as well as, they evidence self-renewal when trapped in gel scaffolds such as collagen. Also, recent studies demonstrate some of the mechanisms involved in the process of making cartilage of adipose-derived stem cells in vitro and their restorative ability in bio-engineered scaffolds in the presence of growth factors. In addition, the important role of non-encoding mRNA molecules (miRNAs) has been identified in the process of chondrogenic differentiation of adipose-derived stem cells. Furthermore, in several studies, the effect of several miRNAs has been confirmed on the regulation of the cartilage differentiation of the adipose-derived stem cells and has also been associated with effective results. In this article, we will present an overview of the advance in adipose-derived stem cells application in cartilage regeneration.

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. It has been proposed that the specific genotypes of Helicobacter pylori (H. pylori) are the causative agents in the development of gastroduodenal diseases, such as chronic atrophic gastritis, peptic ulcerations, and GC. However, disease progression to GC occurs in only a small proportion of infected patients. Recently, we identified a novel polymorphic site in the 3ʹ-end region of H. pylori vacA gene. The vacA c1 genotype increased the risk of GC. This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. Therefore, treatment of H. pylori infection may be an effective way to prevent GC. Expression of cytokines and their associations with inflammatory responses has been shown. Several cytokine polymorphisms, such as IL-1B, IL-8, IL-10, and TNF-α have been considered as risk factors for GC. It has been shown that the interaction of bacterial genotypes and host factors plays an essential role in developing GC. Several altered molecular pathways are involved in the pathogenesis of GC. Micro-RNAs are small, non-coding RNAs of 18-25 nucleotides in length that regulate the expression of target mRNAs. Expression pattern of cancer cells is different compared with the normal cells. Micro-RNAs plays a critical role in apoptosis and classified in two groups: pro- and anti-apoptotic agents. Recent studies have confirmed the oncogenic or tumor suppression role of micro-RNAs in cancer cells. They play a significant role in the GC cell physiology and tumor progression, by translational suppression of target genes. These small RNAs have therefore emerged as a new type of GC biomarker with immeasurable clinical potential. Generally, a variety of micro-RNAs involved in different stages of cancer, including tumorigenesis, angiogenesis, and metastasis. Considering to this issue more than 50% of cancers can be cured, if they were diagnosed in the early stages. Hence, identifying the biomarkers of GC could play an important role in prevention, early diagnosis and rapid treatment of patients. In this review article, we have reviewed the latest findings about bacterial and tissue biomarkers of GC

Although electrical energy is one of the best and cleanest energy sources, the proper protection and utilization of it, always and everywhere is problematic. One of the most important problems is electric shock and the dangers that can sometimes be lost in the lives of people. When a body or part of it is completely located in a strong power supply field or a contact with a device that is connected to a high voltage power supply, the person experiences an electrical burn. Electrical burn injuries account for about 5% of beds in large burn centers. The type of complications due to electrical burns varies according to the location of the current flow, its severity and tissue resistance. But usually the most severe physical and emotional complications are in the upper arms and legs of the body. While electrical injuries primarily result in burns, they may also cause fractures or dislocations secondary to blunt force trauma or muscle contractions. In high voltage injuries, most damage occur internally. On the other hand, psychological trauma and subsequent disability and unemployment problems affect the lives of electric burn victims. Understanding and managing the short-term and long-term complications of electrical burns is important in addition to proper and timely treatment of the injured person. Electric current with a high voltage of 1000 Volts causes a wide and deep burn which may not be estimated exactly at the onset of a visit by the doctor  and also patient himself. So, it should be mentioned the issues legally, to the patients and their relatives, in terms of the severity of lesions and the complications of probable amputation. On the other hand, because prevention is always better than cure, so appropriate information through the mass media can reduce the number patients and their complications. In this review study, introducing various types of electrical burns and the reported statistics, various complications of electrical burn are discussed. Awareness of the incidence of electrical burns in the population and its various complications can help to plan and manage the problems of electric burn injuries, as well as adopting strategies to prevent these incidents.

Head injury is one of the most important types of injury and is responsible for most of the deaths due to trauma. Low-income and middle-income countries face with more risk factors, but they still lack adequate health-care capacity to deal with complications. Trauma literally means the damage and injury, and head injury was defined as physical damage to the brain or skull caused by external forces. Head trauma is an important event. Anyone can fall including toddlers, adults and elders. There are several mechanisms for head injury, including motor vehicle accidents, falls, assault and violence. After the motor vehicle accidents, fall is the second most important cause of head injury. Deaths from falling in countries with lower socioeconomic conditions are higher. To collect the information for this study, the PubMed, Scopus and Google Scholar databases were used. Sixty-four related articles were reviewed from 1980 to 2018. The keywords including "head injury", "head trauma", "brain damage", "fall mechanism", "Iran" and "epidemiology" were used to search the articles. According to the findings of this review fall is the second most common head injury mechanism in Iran. The fall mechanism is more common in the age group of young children and elderly. Also, the incidence of fall mechanism is more in males with head injury than women. In most other countries in the world, fall is the first and the second head injury mechanism. Also, falling from lower altitudes is a more common mechanism than a fall from higher altitude in injury to the head. Falling from lower level is a more common mechanism than fall from higher level in head injuries. In addition, the outbreak of the fall mechanism in children and the elderly with head injuries is more. Despite the efforts that have been made in the past years to determine the pattern of epidemiology of head trauma and its results in Iran, there is not enough information on fall-related head injury. Considering that the head traumatic injury is one of the most common and most dangerous outcomes of fall, the purpose of this review study is to investigate epidemiologic fall-related head injury.

Cancer immunotherapy refers to any intervention that leverages the immune system to eliminate a malignancy. Successful cancer immunotherapies generate an anti-cancer response that is systemic, specific, and durable and overcome to the primary limitations of traditional cancer treatment modalities. In this review paper, the effective methods in immune system to treat cancer, such as immunosuppression in tumor microenvironment (TME), cancer vaccines and T cell adaptive therapy are mentioned. Engineered T cells can use for destruction of the different cancer tissues to diagnose tumor surface antigens. Promotion in culture of T cell methods and their engineering with retroviral vectors that carry T cell receptors or chimeric antigen receptors (CAR) by co-stimulator domains, provide opportunity to treat tumor by T cells. The tumors with high genome mutation, such as lung and melanoma, have severe environmental mutagenesis that is induced by ultra violet light in melanoma and Tobacco in lung cancers. Expression of tumor specific receptors is increased by engineered T cells. The neo-antigens conduct the intensity of intra tumor T cell response. The present of CD8+ in tumor site with more mutation is higher and the mutation load is showed strong relation with the clinical response. In addition to the successful approaches to cancer immunotherapy, the other combination and molecular therapies by nanomaterials are listed. Nanomaterials as efficient modulators and diverse vaccine have been developed in the treatment of cancer. In recent cancer vaccine development has been on subunit vaccines that contain purified tumor antigens or antigenic epitopes as an antigen source. However, soluble bolus-based subunit vaccines typically induce weak cytotoxic T lymphocyte responses which limit their utility for cancer. To overcome this, nanoscale colloids can be used to promote more efficient antigen presentation by acting as phagocytic substrates. Nanomaterials are showed co-suppression and immunization in tumor microenvironment by multiple additive functions in preclinical models. In this manner, they exhibited good prospects because of the good results in overcoming the limitations of current therapies. In this review paper is tried to provide new prospect for therapies and hope it creates highest efficacy and lowest side effects for the treatment of patients in the near future.