Oral Infections in Ancient Human Skulls in 2000 BC/Iron Age, Iran.

Background: Oral infections have been seen in humans since ancient times. Excessive penetration of this infection can cause human death. Most of these infections are gum cysts and abscesses. The cyst creates large hard lumps in the gums, which is causes loose, and protruding teeth and abscesses, causing cavities in the jawbone and teeth. In this article, we have discussed for this infectious disease in 4000 - year - old ancient humans from Qazvin Province, Iran. The bone remains of our research are related to Sagezabad ancient cemetery in Qazvin plain. Methods: We tried to use reliable international atlases to get detailed information about ancient oral infections. The bones were extracted from the 2019 excavation of the Ghara Tappe area of Sagezabad for the Iron Age 2nd and 3rd Qazvin plains of Iran. This cemetery belongs to the period of the Medes Kingdom (pre - Achaemenian kingdom) in Iran. Results: We have discussed one of the ancient cemeteries with a large number of ancient populations. In this cemetery, there are signs of war and infectious diseases on the bones, which can be clearly seen. We have specially mentioned the abscess as the cause of oral infection from Sagezabad cemetery. Conclusion: Oral infection existed in Iran since 2000 BC. Of course, this infection was common in ancient times and even Paleolithic period, like Homo Heidelbergensis.

Investigation of rs8106922 and rs157580 of TOMM40 Gene in Individuals with Late-Onset Alzheimer's Disease in Iran.

Background: We aimed to investigate two polymorphisms, rs8106922 and rs157580 of TOMM40 in Alzheimer's disease (AD). Methods: In the present case-control research, we collected blood samples from 117 AD patients and 130 controls from Alzheimer's Hospital, residents of Tehran, Iran during the winter 2020 to autumn 2022. Following extraction of DNA, Genotyping of TOMM40 polymorphisms rs8106922 and rs157580 were examined by sequencing and ARMS/PCR approaches. We compared distributions of genotypes in both patient and healthy groups using the Chi-Square test. Results: Regarding rs157580, a statistically significant difference was observed in the GA genotype frequency between patient and healthy groups, in both univariate and multivariate modes with these results that have come respectively, and it can be regarded as a protection factor P<0.05).. No significant difference was observed in the frequency of A and G alleles between patient and healthy groups. Besides, concerning rs8106922, the AG genotype frequency in research groups in both univariate and multivariate cases, with these results that have come respectively was significantly different (P=0.003) & (P=0.009). Regarding GG genotype, a statistically significant difference was observed between the patient and healthy groups in both univariate and multivariate cases, respectively (P=0.419) & (P=0.425). Significant differences were observed in the G allele frequency for rs8106922 in the healthy and patient groups (P=0.007), it can be regarded as a potential protective factor. Conclusion: It is possible to consider the TOMM40 gene as one of the potential genes concerning Alzheimer's disease.

CDON Mutation Related to Nose Deformity with Variable Expression in Holoprosencephaly in an Iranian Family: A Case Report.

Holoprosencephaly, a complicated brain abnormality arising from incomplete prosencephalon cleavage, affects both the forebrain and the face. Holoprosencephaly Type 11, with variable expression or partial penetrance, is caused by CDON pathogenic variants associated with the disrupted Sonic Hedgehog (SHH)-pathway. Herein, we aimed to describe a family with genetic nose problems. After counselling and drawing pedigree in Farhud's Genetic Clinic, Tehran, Iran in 2021, DNA extraction of a proband and a few members of his family (patient and control) was conducted. Whole exome sequencing was utilized for detecting the gene and its variant in the proband with a nose deformity. The results were confirmed with Sanger sequencing. This variant was checked in other members by Sanger sequencing. Analysis of the Exome data showed a heterozygous splicing variant in the CDON gene (NM_016952; c.3276+1G>T) in the proband who had a nose deformity and then the results were confirmed with Sanger sequencing. Such a variant was observed in Proband's brother with a nose deformity and was not observed in Proband's cousin with no abnormal phenotype. Recent investigations, in an Iranian family, with a heterozygous splicing CDON mutation as a human candidate gene are discussed for the first time in relation to the likely pathogenesis of facial deformities, particularly nose deformity, in Holoprosencephaly.

Executive Functions and Public Health: A Narrative Review.

Executive functions (EFs) skills are necessary for regulating the thoughts, emotions, and actions which are associated with many aspects of daily functioning. Executive dysfunction (EDFs) is present in a wide range of mental disorders. New study indicates that EFs may predict health behavior and make it easier to engage in a variety of healthy activities. In this narrative review, EFs and public health are briefly discussed. In general, 133 articles met the inclusion criteria (published 2018-2023) which were reviewed. EFs affect the mental and physical health. Besides individual problems, people with mental problems have heavy costs to society. Mental health cannot be considered separately from general health. Consequently, preventive and therapeutic approaches to mental health should be considered not only at the level of the whole society, but also at the global level.

SARS-COV-2 Notable Mutations and Variants: A Review Article.

SARS-COV-2 (COVID-19) the virus that caused an epidemic of sever acute respiratory syndrome is what the world has been dealing with since Dec 2019. As the pandemic continues different variants that emerge during mutations have become the latest concern, with notable examples detected in South Africa, Brazil, and UK. Variants are complicated and each one is a collection of several mutations, all of which have the potential to change the virus in unexpected ways. Studying variants is imperative as they can lead the epidemic to the increase of population immunity. In the present study, we reviewed key mutations and concerning variants according to the WHO tracking Sars-Cov-2 program. Databases were searched through Feb to Mar 2022. Overall, 477 studies were extracted from databases, among them 165 studies included mutations, 239 included COVID-19 variants and 43 included both mutations and variants. At the final step of data screening 24 studies associated to mutations, 31 studies with the highlighted information on COVID-19 variants and 31 studies related to both mutations and variants were extracted for this review article. In conclusion, analyses of the genomic sequence of SARS-CoV-2 indicate that structural proteins are key molecules in the assembly of virus while NSPs can have different biochemical properties and possibly cellular functions.

CRISPR/Cas9 RET Gene Knockout in Medullary Thyroid Carcinoma Cell-lines: Optimization and Validation.

Background: Medullary Thyroid Cancer (MTC) is a very aggressive type of thyroid carcinoma. Mutation in RET proto-oncogene is demonstrated in MTC development. We aimed to knock-out of RET-oncogene using CRISPR/Cas9 genome editing method in MTC cell-lines. Methods: This research was conducted in Shahid Beheshti University of Medical Sciences, Tehran, Iran during 2019-2020. Four different sgRNAs were designed to target exons one, two, and four of RET-oncogene in TT and MZ-CRC-1 cell-lines using bioinformatics tools, then the CRISPR/Cas9 constructs was made. About 72-hours after cell transfection, T7EI method and DNA sequencing were used to confirm the knock-out of RET-oncogene. Expression of RET, Calcitonin genes and RET protein were evaluated by Real-time PCR and ELISA, respectively. Results: The results of T7E1, and DNA sequencing of transfected cells confirmed RET gene knock-out by CRISPR/Cas9. There was a significant decrease in RET gene expression and RET protein in transfected TT and MZ cells compared to controls. The rate of cell apoptosis in transfected cells was significantly increased. Calcitonin gene expression was also significantly reduced in transfected cells. p-RET, p-PI3K, p-AKT, p-MEK, p-ERK protein levels were significantly reduced in TT and MZ transfected cells. Conclusion: For the first time, knock-out of RET gene was performed and confirmed using CRISPR/Cas9. Inhibition of this gene leads to inhibition of the tyrosine kinase RET signal transduction pathway. Therefore, it can be one of the most effective and specific therapeutic goals in the field of Personalized Medicine in the treatment of diseases caused by over activity of RET molecular pathway.

In-Vitro Fertilization Impact on the Risk of Breast Cancer: A Review Article.

BACKGROUND: Due to the increasing prevalence of infertility, the number of referrals to infertility treatment centers has also increased. Nowadays, assisted reproductive technology (ART), including in vitro fertilization (IVF), is a treatment for infertility or genetic problems. Considering the possible consequences of this method among women undergoing in vitro fertilization (IVF) and kids conceived by IVF, extensive research has been conducted in this regard. METHODS: Overall, 100 articles were entered into the study, and relevant articles were searched and extracted from PubMed, Springer, and Google Scholar databases. In IVF procedure, medications such as Clomiphene citrate and gonadotropins are used to stimulate and mature follicles and thus increase ovulation. RESULTS: There are conflicting opinions on this issue. Some findings report a slight increase in cancer risk for hormone-sensitive cancers including breast cancer. The long-term use of IVF medications can increase estrogen hormones and cause excessive expression of genes, resulting in an increased risk of breast cancer, which is one of the most frequent cancers among women. CONCLUSION: There are some risks to be aware of, which followed the hypothesis that long IVF treatment process may lead to breast cancer among IVF candidates. Furthermore, the risk of breast cancer may be increased in those women with a positive family history and related inherited genes. Therefore, women candidates for IVF should be informed of the probable implications of the reproductive therapy techniques.

CRISPR Pioneers Win 2020 Nobel Prize for Chemistry.

Over the last few years, the development of genome editing has revolutionized research on the human genome. Recent advances in developing programmable nucleases, such as meganucleases, ZFNs, TALENs and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas, has greatly expedited the progress of gene editing from concept to clinical practice. The CRISPR has advantages over other nuclease-based genome editing tools due to its high accuracy, efficiency, and strong specificity. Eight years after CRISPR application for human genome edition by Emmanuelle Charpentier and Jennifer A. Doudna, the 2020 Nobel Prize in Chemistry has been jointly given to them for development of CRISPR-Cas9 gene editing, allows scientists to precisely cut and edit of DNA.

A Homozygote Mutation in S-Antigen Visual Arrestin SAG Gene in an Iranian Patient with Oguchi Type One: A Case Report.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness (CSNB) characterized by specific features such as golden-brown discoloration of the fundus called Mizuo-Nakamura phenomenon which is distinguishable by fundoscopy, and retinography. Clinical diagnosis is confirmed through genetic test. Two known genes in pathogenesis of Oguchi disease are SAG and GRK1. A 35-year-old Iranian male exhibiting the clinical features of congenital stationary night blindness, was referred to the genetic clinic of Dr. Farhud, Tehran, Iran in 2012 and examined. Ophthalmic examination including slit-lamp biomicroscopy, perimetry and funduscopy was performed. Additionally, the full-field electroretinography and molecular testing for congenital stationary night blindness were performed. Molecular genetic tests, including the analysis of GSK1 and SAG genes exon-intron boundaries were performed for this patient and his family. According to the sequencing results, we did not find any mutation in GSK1 gene. However, a new homozygote mutation at location chr2:233320735, c.517delC, p.P96LfsX28 was identified in exon four of SAG gene. This deletion causes a frame shift mutation, and premature stop codon that results in deletion of about 281 amino acid residues of S-antigen visual arrestin protein (from entire C-terminal). This mutation was also found in patient's parents and one of his sister as heterozygote form. This is the first molecular evidence for SAG gene mutation in an Iranian family affected with Oguchi disease type 1. The identification of the new c.517delC, p.P96LfsX28 mutation in this family with Oguchi disease can confirm the pathogenicity of this variant.

Convergence Science to Transform Biomedicine: A Narrative Review.

Recently convergence science was proposed and promoted in a large report from US National Science Foundation and Department of Commerce (NSF/DOC). The report was entitled "converging technologies for improving human performance. "It was dealing with converging of four technologies as: Nanotechnology, Biotechnology, Information technology and Cognitive science (NBIC). The report has gained tremendous popularity throughout the academia and scientific world. On Dec 2015 in a monthly meeting of the department of basic science of Iran Academy of Medical Science, the report of NSF/DOC on NBIC has been discussed. A working group has been established for more discussion and application in Iran. Several seminars in this regard have been performed, and presently this technology has been started as pilot in some technical universities in Iran. After US National Research Council (NCR) in the year 2014 and Massachusetts Institute of Technology (MIT) on convergence in biomedicine, the concept opened a new gate to approach solving medical and health care problems; the convergence technology in biomedical sciences has become interested and gained great popularity among the working group of convergence science in academy of medical science. This technology can lead to advances in fighting chronic diseases such as cancer, dementia, psychiatric disorders, disease of aging and others. The following is summary of proposed discussions in several gathered groups of scientists in this field.

Combination of Genetics and Nanotechnology for Down Syndrome Modification: A Potential Hypothesis and Review of the Literature.

Down syndrome (DS) is one of the most prevalent genetic disorders in humans. The use of new approaches in genetic engineering and nanotechnology methods in combination with natural cellular phenomenon can modify the disease in affected people. We consider two CRISPR/Cas9 systems to cut a specific region from short arm of the chromosome 21 (Chr21) and replace it with a novel designed DNA construct, containing the essential genes in chromatin remodeling for inactivating of an extra Chr21. This requires mimicking of the natural cellular pattern for inactivation of the extra X chromosome in females. By means of controlled dosage of an appropriate Nano-carrier (a surface engineered Poly D, L-lactide-co-glycolide (PLGA) for integrating the relevant construct in Trisomy21 brain cell culture media and then in DS mouse model, we would be able to evaluate the modification and the reduction of the active extra Chr21 and in turn reduce substantial adverse effects of the disease, like intellectual disabilities. The hypothesis and study seek new insights in Down syndrome modification.

Happiness and Mental Health in Pre-Operative and Post-Operative Transsexual People.

BACKGROUND: Sex is one of the major social classes in any society. Gender identity as the most fundamental element of human life from beginning to end. While most people with behavior and attitudes appropriate to their physiological gender, but among them are also those sexual behaviors with their physical sex does not match, that say to this group transsexual people. The aim of this study was to investigate happiness and mental health in transsexual individuals before surgery and after surgery. METHODS: This quasi-experimental study, consisted of 42 patients before surgery and after surgery inside Iran in 2016-2017. Snowball sampling method was selected. The instrument was Oxford Happiness Questionnaire (OHQ) and Symptom Check List (SCL25). Data were analyzed using SPSS, t-test independent groups and oneway ANOVA. RESULTS: There was significant difference between transsexual individuals before surgery and after surgery in mean score of happiness (P<0.01) (t=-4/84). Moreover, there was significant difference between the two groups in mean score of mental health (P<0.01) (f=19/13). CONCLUSION: Transsexual individuals after surgery experienced more happiness and mental health than those before surgery.

Cultured Epidermal Melanocyte Transplantation in Vitiligo: A Review Article.

BACKGROUND: The color of the skin is highly heritable but can be influenced by the environments and endocrine factors. Many other factors, sometimes destructive, are also involved in the formation of skin color, which sometimes affects pigmentation patterns. Vitiligo is an autoimmune hypopigmentation painless disorder with appearance of white patches and psychological effects on patients. It is a disease in which melanocytes of the skin are destroyed in certain areas; therefore depigmentation appears. METHODS: We studied more than 60 articles. Several therapeutic methods have been used to return the color of skin in vitiligo. These methods include non-invasive treatment and surgical techniques. Among all these therapies, cell transplantation is an advanced procedure in regenerative medicine. Extraction of melanocytes from normal skin and then their cultivation in the laboratory provides a large number of these cells, the transplanting of which to depigmentation areas stimulates the site to irreversibly produce melanin. RESULTS: The transplantation methods of these cells have been evolved over many years and the methods of producing blister have been changed to the injection of these cells to the target sites. CONCLUSION: In this review, autologous cultured melanocyte transplantation has been considered to be the most viable, safe, and effective method in the history of vitiligo treatments.

A Comprehensive, Epidemiological and Ecological Descriptive Study on Vitamin D Status in Iran (308005 People, from 2009-2018).

BACKGROUND: Vitamin D is an essential substance for absorption of calcium and phosphorus from intestine so it is vital for muscles and skeletal development. Deficiency of this vitamin is pandemic. The vitamin D status depends on the different factors such as UV exposure, diet, and ecological features of living location, age and gender. The aim of this study was to describe the vitamin D level in different provinces of Iran and to investigate the association between vitamin D status and multiple variables. METHODS: We collected the serum 25(OH)D (Vitamin D) level data of 308,005 people referred to different laboratories from 30 provinces of Iran and organized them by each province, year, age, gender, precipitation, latitude and longitude, and humidity over 10 yr (2009-2018). Data were analyzed to find out the correlation between age, gender, longitude and latitude, humidity and sum of precipitation. RESULTS: West Azerbaijan had the highest level of vitamin D with a mean level of 33.24 and a standard deviation of 32.001, and North Khorasan had the lowest level with a mean level of 14.46 and a standard deviation of 8.980 among 30 provinces of Iran. The correlation between all studied variables (age, and gender, latitude and longitude, humidity, the sum of precipitation) was significant (P<0.001). CONCLUSION: The average total vitamin D level in Iran is 25.41 ng/ml, which is within the area of deficiency. Vitamin D is associated with age, and gender, latitude and longitude, humidity, the sum of precipitation. So changes in any of these variables can lead to vitamin D alteration.