Adipose-derived human mesenchymal stem cells seeded on denuded or stromal sides of the amniotic membrane improve angiogenesis and collagen remodeling and accelerate healing of the full-thickness wound.

Several strategies have been proposed to enhance wound healing results. Along with other forms of wound dressing, the human amniotic membrane (HAM) has long been regarded as a biological wound dressing that decreases infection and enhances healing. This study investigates the feasibility and effectiveness of wound healing using decellularized HAM (dAM) and stromal HAM (sAM) in combination with adipose-derived human mesenchymal stem cells (AdMSCs). The dAM and sAM sides of HAM were employed as wound dressing scaffolds, and AdMSCs were seeded on top of either dAM or sAM. Sixty healthy Wistar rats were randomly divided into three groups: untreated wound, dAM/AdMSCs group, and sAM/AdMSCs group. The gene expression of VEGF and COL-I was measured in vitro. Wound healing was examined after wounding on days 3, 7, 14, and 21. The expression level of VEGF was significantly higher in sAM/AdMSCs than dAM/AdMSCs (P ≤ 0.05), but there was no significant difference in COL-I expression (P ≥ 0.05). In vivo research revealed that on day 14, wounds treated with sAM/AdMSCs had more vascularization than wounds treated with dAM/AdMSCs (P ≤ 0.01) and untreated wound groups on days 7 (P ≤ 0.05) and 14 (P ≤ 0.0001), respectively. On days 14 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), and 21 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), the collagen deposition in the wound bed was significantly thicker in the sAM/AdMSCs and dAM/AdMSCs groups compared to untreated wounds. The study demonstrated that the combination of sAM and AdMSCs promotes wound healing by enhancing angiogenesis and collagen remodeling.

Copy number analysis from whole-exome sequencing data revealed a novel homozygous deletion in PARK7 leads to severe early-onset Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative disease characterized by both motor neuron and non-motor neuron symptoms, is the most frequent neurodegenerative disease after Alzheimer's disease. Both genetic and environmental factors take part in disease etiology. Most cases are considered complex multifactorial diseases. About 15% of PD appear in the familial form, and about 5% of all cases arise from a single gene mutation. Among Mendelian causes of PD, PARK7 is one of the autosomal recessive forms due to loss-of-function mutations in both gene alleles. Both single nucleotide variants (SNVs) and copy number variations (CNVs) are observed in PARK7. This study presents an Iranian family with familial PD where some relatives had psychiatric disorders. A homozygous 1617 bp deletion in a female with early-onset PD was detected through copy-number analysis from whole-exome sequencing (WES) data in this consanguineous family. Further investigation by surveying microhomology revealed that the actual size of the deletion is 3,625 bp. This novel CNV that was in the PARK7gene is supposed to co-relation with early-onset PD and infertility in this family.

Whole-Exome Sequencing Study of Consanguineous Parkinson's Disease Families and Related Phenotypes: Report of Twelve Novel Variants.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder with motor and nonmotor symptoms. Recent studies demonstrate various susceptibility loci and candidate genes for familial forms of the disease. However, the genetic basis of the familial form of early-onset PD (EOPD) is not widely studied in the Iranian population. Therefore, the present study aimed to investigate the possible causative genetic variants responsible for developing EOPD among Iranian patients. Iranian patients with a clinical diagnosis of Parkinson's disease were evaluated, and 12 consanguineous families with at least two affected individuals with early-onset PD (EOPD) were chosen to enroll in the present study. An expert neurologist group examined these families. Whole-exome sequencing (WES) was performed on PD patients, and the possible causative genetic variants related to the development of PD were reported. Exome sequencing (WES) was performed on every PD patient and revealed that patients had novel genetic variants in PRKN, PARK7, and PINK1 genes. All the genetic variants were in homozygous status and none of these variants were previously reported in the literature. Moreover, these genetic variants were "pathogenic" based on bioinformatic studies and according to the American College of Medical Genetics (ACMG). The present research revealed some novel variants for EOPD among the Iranian population. Further functional studies are warranted to confirm the pathogenicity of these novel variants and establish their clinical application for the early diagnosis of EOPD.

Preclinical and Clinical Aspects of using Tazemetostate in Human Cancers.

Epigenetic drugs are novel drug categories with promising effects in different cancers. Tazemetostate is among the drugs that were recently used in clinical settings, especially in the treatment of specific tumors and lymphomas. There are a growing number of ongoing clinical trials evaluating the safety and efficacy of tazemetostate in different cancers. The present review addressed the available preclinical studies evaluating the combination of tazemetostate and other chemotherapy agents in treating different cancers and summarized the limited clinical evidence available regarding the efficacy of this novel Enhancer of Zeste Homolog 2 (EZH2) inhibitor in cancer. Based on the available clinical studies, tazemetostate could be considered a safe epigenetic agent with limited adverse events for treating specific types of lymphomas and solid tumors. However, the superiority of using tazemetostate over other chemotherapy agents in patients with cancer as well as using the drug for other clinical conditions, including non-alcoholic steatohepatitis, needs further investigation. Moreover, the effect of tazemetostate on human germline cells is clearly evaluated as some animal studies demonstrated that the drug can affect germline epigenome suggesting further studies on this issue.

Evaluation of COVID-19 Trend in Iran; Population Response to the Recent Pandemic Overtime.

Relative internet search volumes (RSV) is now being consider as a measurement of awareness for most of the trending topics. During the recent coronavirus disease (COVID-19) outbreak, many researchers used the RSVs to interpret the population responses to the pandemic in various ways. By using the RSVs searched by Persian language people, we demonstrated that the Iranian people increased their knowledge and awareness of COVID-19 during the early phases of the disease before the first peak. However, their relative searches about the COVID-19 and its clinical symptoms decreased gradually despite of the gradual rise of the confirmed cases. Their less tendency to seek information about the COVID-19 could be one of the possible explanation for the increasing number of confirmed cases even several days after easing the disease related lockdown.

Genotyping of ABCC8, KCNJ11, and HADH in Iranian Infants with Congenital Hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is a heterogeneous disease with various underlying genetic causes. Among different genes considered effective in the development of CHI, ABCC8, KCNJ11, and HADH genes are among the important genes, especially in a population with a considerable rate of consanguineous marriage. Mutational analysis of these genes guides clinicians to better treatment and prediction of prognosis for this rare disease. The present study aimed to evaluate genetic variants in ABCC8, KCNJ11, and HADH genes as causative genes for CHI in the Iranian population. METHODS: The present case series took place in Mashhad, Iran, within 11 years. Every child who had a clinical phenotype and confirmatory biochemical tests of CHI enrolled in this study. Variants in ABCC8, KCNJ11, and HADH genes were analyzed by the polymerase chain reaction and sequencing in our patients. RESULTS: Among 20 pediatric patients, 16 of them had variants in ABCC8, KCNJ11, and HADH genes. The mean age of genetic diagnosis was 18.6 days. A homozygous missense (c.2041-21G > A) mutation in the ABCC8 gene was seen in three infants. Other common variants were frameshift variants (c.3438dup) in the ABCC8 gene and a missense variant (c.287-288delinsTG) in the KCNJ11 gene. Most of the variants in our population were still categorized as variants of unknown significance and only 7 pathogenic variants were present. CONCLUSION: Most variants were located in the ABCC8 gene in our population. Because most of the variants in our population are not previously reported, performing further functional studies is warranted.

The Potential Impact of Statins in the Treatment of Patients with COVID-19 Infection.

INTRODUCTION: Statins are cholesterol-lowering drugs that also have anti-inflammatory/ immunomodulatory properties, and have been suggested as an adjunct therapy for COVID-19. METHODS: To investigate the clinical impact of statins as a potential therapeutic approach in the treatment of cases infected with COVID-19, a systematic search was performed using PubMed and Google Scholar databases. To extend the search results, a set of keywords were used as follows: ("corona virus" OR "Covid-19" OR "SARS-Cov-2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR coronavirus) AND (Statins), alongside a manual search in Google Scholar search engine. RESULTS: It has also been suggested that statins could influence the entry of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into cells by altering the expression of the angiotensin-converting enzyme 2 (ACE2) and CD143 receptors. Statins may be beneficial for COVID-19 patients according to its pleiotropic effects, although, from the clinical aspect, these pleiotropic effects of statins may not be as strong as in preclinical phase on COVID-19. A retrospective study showed favorable effects for statins in SARS-CoV-2 infection. CONCLUSION: Patients with SARS-CoV-2 infection have a high risk of cardiovascular and thrombotic complications and pleiotropic effects of statins may help manage the COVID-19. There is growing evidence that supports the need for trials of statin treatment in COVID-19 infection.

SARS-CoV-2 Liability: The Hidden Mystery Behind Its Presentation in Children.

Coronavirus disease 2019 (COVID-19) is now of global concern because of its rapid dissemination across the globe. It is unclear whether COVID-19 is as hazardous as previous coronavirus outbreaks, though there are many overlapping similarities between these viruses. An important similar feature includes the virus's pathogenicity in pediatric populations. Additionally, genetic factors are recognized as important contributors to infectious disease susceptibility. Further understanding of this area can help make sense of the pathogenesis of COVID-19 and the varying clinical spectrums of the disease. The available data suggests that COVID-19 most likely produces mild symptoms in a healthy pediatric population regardless of their age, and recovery appears to occur without serious sequelae in the vast majority. However, the available data regarding the detailed repercussions of COVID-19 in children is very limited. To date, only some theoretical issues could be responsible for the COVID-19 susceptibility in pediatric patients, including a more intact but mature immune system within the respiratory system, possible role of viral interference in pediatric populations that are more often infected with common respiratory viruses, possible role of gut-lung axis, and a respiratory system with different amounts of cellular receptors for COVID-19 virus. Moreover, there is little data available on the genetic risk factors for COVID-19, and future research should aim to cover this gap in knowledge. This chapter aims to summarize the recently published data on the impact of COVID-19 in the pediatric population and to systematically review the available evidence of genetic risk factors for COVID-19.

Familial combined hyperlipidemia: An overview of the underlying molecular mechanisms and therapeutic strategies.

Among different types of dyslipidemia, familial combined hyperlipidemia (FCHL) is the most common genetic disorder, which is characterized by at least two different forms of lipid abnormalities: hypercholesterolemia and hypertriglyceridemia. FCHL is an important cause of cardiovascular diseases. FCHL is a heterogeneous condition linked with some metabolic defects that are closely associated with FCHL. These metabolic features include dysfunctional adipose tissue, delayed clearance of triglyceride-rich lipoproteins, overproduction of very low-density lipoprotein and hepatic lipids, and defect in the clearance of low-density lipoprotein particles. There are also some genes associated with FCHL such as those affecting the metabolism and clearance of plasma lipoprotein particles. Due to the high prevalence of FCHL especially in cardiovascular patients, targeted treatment is ideal but this necessitates identification of the genetic background of patients. This review describes the metabolic pathways and associated genes that are implicated in FCHL pathogenesis. We also review existing and novel treatment options for FCHL. © 2019 IUBMB Life, 71(9):1221-1229, 2019.

Prevalence of ß-Thalassemia Mutations among Northeastern Iranian Population and their Impacts on Hematological Indices and Application of Prenatal Diagnosis, a Seven-Years Study.

BACKGROUND AND OBJECTIVE: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit ß (HBB) gene. In a study of ß-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran, we aimed to recognize the most common mutations in the region. We also investigated a possible link between these mutations and some of the relevant hematological indices. METHODS: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical HBB mutations among 1593 individuals, suspected of having a mutated HBB allele from March/2011 to January/2018. Sanger sequencing of HBB had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables. RESULTS: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), codons 8/9 (4.79%), codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.91%), codon 5 (2.75%), IVS-I-110 (2.51%), -88 (2.20%) and other mutations were less than 2% of all of the reported mutations. 644 conceptions were subjected to prenatal diagnosis, using chorionic villus sampling. 118 cases were reported as normal. 352 cases were detected as carriers. 174 cases were diagnosed as affected. There was a significant difference in mean corpuscular volume and hemoglobin A2 levels between the nine most commonly reported mutation types (p<0.001). CONCLUSION: This study makes a reliable guide for ß-thalassemia diagnosis in the region. The possibility of a correlation between HBB mutations and hematological indices opens a gate of future investigations.

Long term effect of vaginal delivery and cesarean section on female sexual function in primipara mothers.

INTRODUCTION: Pregnancy and birth giving are two of the most important and common effective factors influencing female sexual function. Sexual dysfunction can affect women's quality of life and marriage. This research tried to determine the relation between labor type and long term sexual function in primipara women of Sabzevar, Iran. METHODS: This cross-sectional study took place in Sabzevar healthcare system in 2014. Study population was chosen by random sampling from every primipara woman who had delivered 2 years ago, in Sabzevar Hospitals. A total number of 177 primipara women were enrolled in this study after signing an informed contest. Sexual function of mothers was determined by validated Persian version of female sexual function index (FSFI). SPSS statistical software version 19 and descriptive and inferential statistics such as percentage, mean, standard deviation, Chi square, student t-test and fisher exact test were used to analyze data. RESULTS: Among the study population, 69.5% had natural vaginal delivery (NVD) and 30.5% had caesarean section (C/S). The overall FSFI score was not significantly different in women undergoing NVD or C/S (p=0.23). Also, no significant relation was found between delivery method and urinary (p=0.07) and fecal incontinency (p=0.6). Female sexual function was prominent in women with urinary (p=0.015) and fecal incontinency (p=0.018). CONCLUSION: The results of present study showed that delivery method has no long-term effect on female sexual function and appropriate education about the sexual issues after delivery and effect of birth giving on sexual function are necessary for this group of society.

Effect of Fluoxetine Administration on Clinical and Echocardiographic Findings in Patients with Mitral Valve Prolapse and Generalized Anxiety Disorder: Randomized Clinical Trial.

BACKGROUND: Mitral valve prolapse (MVP) is accompanied by mental disorders including anxiety, which has similar presentations as MVP. It is hypothesised that treatment of anxiety might reduce the symptoms of MVP. OBJECTIVE: The aim of this study was to assess the clinical and echocardiographic effects of fluoxetine administration in patients with MVP and anxiety. METHODS: This randomized clinical trial was conducted on patients with documented MVP and generalised anxiety disorder (GAD) who were referred to Mashhad University of Medical Sciences cardiology clinics, Mashhad, Iran in 2015. Subjects were randomly assigned to intervention group who received propranolol and fluoxetine (both at 10 mg/day) and control group who received 10 mg/day propranolol. Assessments included echocardiography and GAD-7 questionnaire and rating of chest pain, that were performed at baseline and then weekly for 4 weeks. Analysis was performed using the Mann-Whitney U test and Two-way Repeated Measures Analysis of Variance (ANOVA). RESULTS: Sixty patients (25 male/ 35 female) with a mean age of 22.9 ± 2.5 years were studied in two groups of intervention (n = 30) and control (n = 30). GAD score was significantly higher in the intervention group (17.37 ± 1.61) compared with the control group (14.17 ± 0.83) (p<0.001). No significant difference was observed for changes in left atrium diameter, mitral annular diameter, left ventricular diameter or ejection fraction (p>0.05). Pain severity was reduced significantly more in control group (3.27 ± 1.26) compared to intervention group (2.80 ± 0.85) after treatment (p<0.001). CONCLUSIONS: This study revealed that the co-administration of fluoxetine and propranolol may not only have no effective in improving echocardiographic changes of MVP but may also aggravate subjective findings of patients with MVP and GAD. TRIAL REGISTRATION: The trial is registered at the Iranian Clinical Trial Registry (IRCT.ir) with the IRCT identification number IRCT2014102819721N1. FUNDING: This research has been financially supported by Research Council of Sabzevar University of Medical Sciences.

Consanguinity and isolated atrial septal defect in North East of Iran.

BACKGROUND AND OBJECTIVES: The rate of consanguineous marriage is high in Middle Eastern countries such as Iran. The relationship between consanguineous marriage and congenital heart disease is discussed in some studies, but there is not much data for relationship between atrial septal defect (ASD) and consanguineous marriage. The aim of this study was to evaluate the relationship between consanguineous marriage and ASD echocardiographic characteristics. DESIGN AND SETTINGS: This was a cross-sectional study approved by Mashhad University of Medical Sciences ethics committee and took place in Mashhad, Iran, for a period of 3 years from August 2008 till September 2011. METHODS: In this cross-sectional study, 113 ASD patients participated and they were categorized into 3 groups on the basis of family relationship between their parents: first group-"no relationship," second group- "third degree relationship," and third group- "far relationship." RESULTS: Among the 54 male and 59 female ASD patients, the most prevalent type of ASD was ASD secundum (85.0%) followed by sinus venosus (8.8%). A total of 56% patients were present in the first group and 15% and 29% in the second group and the third group, respectively." The relationship between consanguinity and type of ASD (P < .001) and gender (P < .001 each) was observed. The relationship between the age of onset of disease and consanguinity (P=.003) was also observed. CONCLUSION: Considering the fact that there is a high prevalence of ASD and consanguineous marriage in Iran and bearing in mind the results of the present study, we recommend educating couples about the outcomes of consanguineous marriage in pre-marriage counseling.