Alireza Biglari

Tehran University of Medical Sciences | TUMS · Department of Medical Genetics

Background Limb girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders with a very variable clinical presentation and overlapping traits. The clinical symptoms of LGMD typically appear in adolescence or early adulthood. Genetic variation in the dysferlin gene (DYSF) has been associated with LGMD. Methods We...

The immunotherapeutic application of interleukin-2 (IL-2) in cancer treatment is limited by its off-target effects on different cell populations and insufficient activation of anti-tumor effector cells at the site of the tumor upon tolerated doses. Targeting IL-2 to the tumor microenvironment by generating antibody-cytokine fusion proteins (immunoc...

Background: Although structural heart disease is frequently present among patients who experience sudden cardiac death (SCD), inherited arrhythmia syndromes can also play an important role in the occurrence of SCD. CPVT2, which is the second-most prevalent form of CPVT, arises from an abnormality in the CASQ2 gene. Objective: We represent a novel C...

Background This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. Materials and methods 194 volunteers enrolled the study who were previously primed with 2 doses of ChAd...

Background: Arsenic three oxide (As2O3) is the treatment choice for acute promyelocytic leukemia (APL). Little is known about possible risk factors with predictive value for toxicity caused by As2O3. Biomethylation is considered to be a major pathway of detoxification for inorganic arsenics (iAs). Arsenic Methyltransferase (AS3MT) is one of the key...

The present study aims to provide an insight to the comprehensive efforts of Pasteur Institute of Iran (PII) regarding COVID-19 management, research, achievements, and vaccine production, though there are many challenges. The relevant literature review was investigated through national and international database and also reports from the related re...

COVID-19 pandemic has been managed through global vaccination programs. However, the antibody waning in various types of vaccines came to notice. Hereby, PastoCovac Plus as a protein subunit vaccine was investigated in immunized health care workers by COVAXIN (BBV152). The booster vaccine was recommended at least three months post the second dose o...

Breast cancer is the most common malignancy in women worldwide. Administration of oncolytic viruses is one of the novel promising cancer therapy approaches. Replication of these viruses is usually limited to cancer cells that have interferon (IFN) signaling defects. However, Interferon signaling is not completely impaired in all cancer cells which...

Although over three years have passed since the onset of the Covid-19 pandemic, this disease remains a significant public health concern in Iran and around the world. It is essential to acknowledge that the current situation does not signify an end to the epidemic, and measures must be taken across various levels of prevention, treatment, and polic...

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals wh...

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of...

Background: Long QT syndrome (LQTS) is a lethal cardiac condition. However, the clinical implementation of genetic testing has now made LQTS eminently treatable. Next-generation sequencing has remarkable potential for both clinical diagnostics and research of LQTS. Here, we investigated the genetic etiology in an LQTS-suspected Iranian pedigree by...

Background Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-b...

Background SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to eva...

Breast cancer is the most common malignancy in women worldwide. Administration of oncolytic viruses is one of the novel promising cancer therapy approaches. Replication of these viruses is usually limited to cancer cells that have interferon (IFN) signaling defects. However, Interferon signaling is not completely impaired in all cancer cells which...

Objectives To evaluate a heterologous vaccination scheme in children 3-18 y/o combining two SARS-CoV-2 r-RBD protein vaccines. Methods A phase I/II open-label, adaptive and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequ...

Background The present study aims to show the comprehensive effort of Pasteur Institute of Iran and its scientists regarding COVID-19 chaos management, related studies, achievements and vaccine production though there were many imposed challenges. Methods The relevant literature review was done through the associated data from national and interna...

Context: In vitro maturation (IVM) of oocytes is an alternative approach for patients with polycystic ovary syndrome (PCOS) predisposing to ovarian hyperstimulation syndrome (OHSS). Transcriptomic analysis of cumulus cells (CC) may help make IVM more efficient. The aim of this study was to examine the impact of miR-144 and miR-224 and their candid...

Background SOBERANA 02 have been evaluated in phase I and IIa studies comparing homologous vs. heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults. Method Phase IIb was a parallel, multicenter, adapti...

Despite substantial efforts, no effective treatment has been discovered for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. Therefore, vaccination to reach herd immunity is the ultimate solution to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to evaluate the potency, toxicity, and protection of...

Although high-dose IL-2 has clear antitumor effects, severe side effects like severe toxicity and activation of Tregs by binding of IL-2 to high-affinity IL-2R, hypotension, and vascular leak syndrome limit its applications as a therapeutic antitumor agent. Here in this study, a rational computational approach was employed to develop and design nov...

Background: This study investigated the possible role of Genistein as a combination with Imatinib in controlling leukemia cell line proliferation. Methods: Three cell lines, K562, Kcl22, and CCRF, were cultured and analyzed for MTT, LDH, apoptosis, and cycle cell gene expression in the presence of different dosages of Imatinib and Genistein in comb...

Background: We report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults in a phase IIb clinical trial. Method: This phase IIb trial was designed as parallel, multicentre, adaptive, double blind, randomized and placebo-controlled. Subjects (N=810) aged 19-80 years were rando...

Background and aims Motility and morphological defects of spermatozoa can cause male infertility. Sperm RNAs are related to sperm quality. They are considered to have clinical values as a biomarker for assessing sperm quality and fertility potential. The annulus, located in the mammalian sperm tail, is required for motility and terminal differentia...

[This corrects the article DOI: 10.1016/j.hlpt.2021.100506.].

Background: Recurrent pregnancy loss (RPL) is a multifactorial disorder which affects up to 5% of couples around the world. Several factors are considered to be involved in RPL; but, the etiology remains unexplained in 35-60% of cases. The aim of this study was to assess the frequency of risk factors associated with RPL in a group of our clinic cl...

The present study investigated the potential of vascular endothelial growth factor (VEGF) promoter to derive cytosine deaminase (CD) transfected by polyamidoamine (G4-PAMAM) dendrimers to 4T1 murine breast cancer cell line as gene-directed enzyme/prodrug therapy. The VEGF promoter and cytosine deaminase gene were cloned into the pEGFP-N1vector from...

Introduction: Semaphorin 3A (Sema 3A) is a secreted protein, which plays an integral part in developing the nervous system. It has collapse activity on the growth cone of dorsal root ganglia. After the development of the nervous system, Sema 3A expression decreases. Neuropilin 1 is a membrane receptor of Sema 3A. When semaphorin binds to neuropilin...

Introduction: The CC chemokine receptor 5 (CCR5) is known as the main co-receptor in human immunodeficiency virus (HIV) infection. Accumulating evidence verified 32bp deletion in both alleles of CCR5 provides natural resistance to HIV infection. Accordingly, recent therapeutic approaches are based on gene and cell therapies by inducing this resista...

Objective Recurrent pregnancy loss (RPL) is a common infertility-related complication that affects approximately 1-3% of women worldwide. Known causes of etiology are found in approximately half the cases but the other half remain unexplained. It is estimated that several thousands of genes contribute to reproductive success in mammals and the gene...

Background: Dopamine and serotonin receptors are present in lymphocytes, macrophages, and neutrophils, and have a mediating role in the immune system to respond to infections, including bacterial tuberculosis. Materials and methods: In this study, at first, the changes in the expression pattern of 5 dopamine and 2 serotonin (5HTR2B & 5HTR2C) gen...

Background Spinal cord injury (SCI) activates a cascade of signaling pathways which results in impaired sensory and motor function without restoration of function due to the very limited self-regenerative ability of the spinal cord. As a novel treatment, combination therapy can offer effective repair for SCI regeneration. In this study, a polymeric...

Background: Triploidy is one of the most common chromosome abnormalities affecting human gestation and accounts for an important fraction of first-trimester miscarriages. Triploidy has been demonstrated in a few cases of recurrent pregnancy loss (RPL) but its molecular mechanisms are unknown. This study aims to identify the genetic cause of RPL as...

The prevalence of primary immunodeficiency (PID) is rather high in Iran compared to the world average, mainly due to the high rate of consanguineous marriage. Despite that, little genetic information is available about primary immunodeficiencies in Iran. Autosomal recessive hyper IgE syndrome (AR-HIES) is a severe type of immunodeficiency, mainly c...

Background: Numerous studies confirmed significant decrease in tissue DCN expression is associated to tumor progression and metastasis in certain types of cancer including PC. However, the potential prognostic value of tissue DCN in PC has not yet been investigated. Methods: A total number of 40 PC and 42 patients with BPH were investigated for...

Severe combined immunodeficiency (SCID) comprises a heterogeneous group of genetic disorders caused by early defects in the development and function of T cells. Other lymphocyte lineages (B and/or natural killer cells) are variably affected. With a worldwide frequency of approximately 1:50,000 live births, SCID may result from diverse mutations in...

Background and Objective: Recurrent pregnancy loss (RPL) is a multifactorial disorder and defined as two or more consecutive miscarriages that affects up to 5% of clinical pregnancies. Several factors are associated with RPL, however, in 35–60% of miscarriages the etiology remains unexplained. In recent years, the advent of high throughput technolo...

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Several factors are known to contribute to the development and progression of diabetic nephropathy. Different microRNAs have been shown to contribute in the pathogenesis of DN. This study, aimed to evaluate the expression level of circulating miR-155 i...

Background: Congenital Heart Disease (CHD) occurs in nearly 1% of newborns due to genetic and environmental factors. There are many genes involved in CHD. Variants of Gap Junction Protein Alpha 1 (GJA1), Zic Family Member 3 (ZIC3), Nodal Growth Differentiation Factor (NODAL), and Forkhead Box H1 (FOXH1) genes are common to develop CHD. Objectives:...

Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy of the peripheral nervous system with a wide range of severity and age of onset. CMT patients share similar phenotypes which make it often impossible to identify the disease types based on clinical presentation and electrophysiological studies alone. In recent years, novel g...

Objective(s): MicroRNAs (miRNAs) could regulate many cellular processes such as proliferation and differentiation. let-7a miRNA is one of the key regulators in the developmental transition of retinal progenitor cells into differentiated cells. Current evidence suggests that mesenchymal stem cells (MSCs) can isolate from various tissues such as bone...

Background Congenital heart disease (CHD) is the most common birth defect and a major health problem around the world. However, its exact etiology has remained unclear. Among various genetic contributing factors, GATA4 transcription factor plays a significant role in the CHD pathogenesis. In this study, GATA4 coding sequence was screened in Iranian...

recurrent pregnancy loss and infertility

Background & Objectives: This research aimed to determine the relationship between awareness of Islamic citizenship rights and organizational similar-to-me of education managers of Zanjan University of Medical Sciences, Zanjan, Iran. Materials and Methods: This descriptive and correlational research was performed on all education department manager...

Aims: Breast cancer is a high prevalence cancer among women worldwide. 15-20% of breast cancer cases are triple-negative with a poor prognosis. miRNA aberrant expression is one of the reasons of cancer development and metastasis. Exosomes are vesicles that carry cargos such as miRNAs to other cells. Therefore, we hypothesized that miRNAs transport...

Pro-thrombotic and inflammatory changes play an important role in cardiovascular morbidity and mortality, resulting from short-term exposure to fine particulate air-pollution. Part of those effects has been attributed to the ultra-fine particles (UFPs) that pass through the lung and directly contact blood-exposed and circulating cells. Despite UFP-...

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Several factors are known to contribute to the development and progression of diabetic nephropathy. Different microRNAs have been shown to contribute in the pathogenesis of DN. This study, aimed to evaluate the expression level of circulating miR-155 in...

Abstract Background: Reduction in the level of tissue decorin is a hallmark of many types of cancer including breast carcinoma. However, reduced decorin expression has also been reported in several types of benign tumors to the extent that it has been proposed as a tissue marker to differentiate malignant from benign tumors. The aim of this study...

Breast cancer is one of the most prevalent cancers in women. Triple‐negative breast cancer consists 15% to 20% of breast cancer cases and has a poor prognosis. Cancerous transformation has several causes one of which is dysregulation of microRNAs (miRNAs) expression. Exosomes can transfer miRNAs to neighboring and distant cells. Thus, exosomal miRN...

Background Trisomy 22 mosaicism is a rare autosomal anomaly with survival compatibility. Recognition of the complete trisomy 22 which is incompatible with life from the mosaic form is critical for genetic counseling. Affected mosaic cases have prevalent clinical presentations such as webbed neck, developmental delay, abnormal ears, cardiac disorder...

Background: Despite the clear role of the Nkx2-5 gene mutations as the trigger for Congenital Heart Disease (CHD) in different populations, the condition of these mutations in our population remains obscure. Objectives: The present study aimed to assess different Nkx2-5 gene mutations in a sample of Iranian patients with CHD. Patients and Methods:...

Genetic contributing factors to non-syndromic hearing loss (NSHL) are remarkably diverse spanning over autosomal to X-linked to mitochondrial inheritance patterns. Facing a quite unconventional pedigree, here we report implementation of whole exome sequencing (WES) to uncover mitochondrial pathogenic variant in a six-generation Iranian family with...

Background: MiR-152 has been reported as a tumor suppressor microRNA that is downregulated in a number of cancers, including colorectal cancer (CRC). A recent study suggested that miR-152 could be one of the key regulators of CRC. The aim of this study is to investigate the role of miR-152 in CRC and its mechanisms. Methods: The pCMV-GPF-miR-152...

Objective: Diabetic nephropathy is a long-term complication of diabetes and is manifested as reduced glomerular filtration rate, increased urinary albumin excretion, and glomerular lesions. The study aim was to determine the expression level of serum cell-free mir-93 in diabetic patients with or without DN and compare that to healthy controls. Mate...

Background and Objective: Spinal cord injury (SCI) leads to the loss of axons and cell death via necrosis and apoptosis, eventually resulting in sensory and motor dysfunction. The aim of this study was to evaluate the effects of valproic acid on the inhibition of apoptosis and the improvement of motor function in the rat model of spinal cord injury...

In recent years, in light of the promising potentials of mesenchymal stromal/stem cells (MSCs) for carrying therapeutic anticancer genes, a complete revisitation on old chemotherapy-based paradigms has been established. This review attempted to bring forward and introduce the novel therapeutic opportunities of using genetically engineered MSCs. The...

Objective(s) Extracellular matrix (ECM) is composed of many kinds of glycoproteins containing glycosaminoglycans (GAGs) moiety. The research was conducted based on the N-Acetylgalactosamine (GalNAc) degradation of ECM components by α-N-acetylgalactosaminidase (Nagalase) which facilitates migration and invasion of cancer cells. This study aims to in...

Constitutive activation of nuclear factor-κB (NF-κB) stimulates cell proliferation and metastasis, and inhibits apoptosis in breast cancer. Transforming growth factor-β (TGF-β) signaling pathway is deregulated in breast cancer progression and metastasis. The aim of the present study was to investigate the inhibitory effects of the two small leucine...

Background and Objective: CCR5 is known as a main co-receptor in HIV infection. Many studies demonstrated that 32bp deletion in both CCR5 alleles provide natural resistance to HIV infection, so new treatment approaches are based on inducing this resistance by means of gene and cell therapies. This projects aim was the discovery of suitable candidat...

Studies on patient-specific human-induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet-rich plasma (PRP)...

Background: Periodontal disease has a multifactorial etiology. A combination of microbial agents and environmental, habitual, systemic, and genetic risk factors is responsible for the development of periodontal disease. Host immune response causes the destruction of tooth-supporting structure and eventual tooth loss. This study aimed to assess the...

Objectives: Diabetic nephropathy is an important long-term complication of diabetes mellitus which appears to be partially mediated by an increase in secretion of transforming growth factor-β (TGF-β). Fibromodulin, the small leucine-rich proteoglycan, has been proposed to be the potent TGFβ1 modulator. In this study, the therapeutic effects of rec...

Phenylketonuria (PKU) is an autosomal recessive disease which results from mutations in the phenylalanine hydroxylase (PAH) gene. The aim of this study was the identification of sixteen different mutations in Iranian patients with hyperphenylalaninemia. The mutations were detected during the characterization of PAH genotypes of 39 PKU patients from...

Comparison between the efficacy of ceftriaxone and monocytes on improvement of neuron protection and functional recovery after spinal cord injury (SCI) in rat. Rats were randomly divided into three groups of ten. Spinal cord injury was performed on rats under general anesthesia using the weight dropping method. Ceftriaxone was injected intraperiton...

Transforming Growth Factor-beta (TGF-β) activation appears to be crucial for tissue injury in Diabetic Nephropathy (DN). Fibromodulin, the small leucine-rich proteoglycan, has been proposed to be the potent TGF-β modulator. In this study, the therapeutic effects of fibromodulin in the kidneys of streptozotocin (STZ)-induced diabetic rats were inves...

Background and Objective: Breast cancer, assumed as a difficult -to -treat disorder across the world, is the most common malignancy among women. Over decades, significant advances in breast cancer immunotherapy and tumor immune biology have been brought about. In vitro studies of the effect of various cytokines have been conducted in breast tumor....

Ciprofloxacin HCL is a fluoroqinolone antibiotic, effective against a wide range of Gram positive and Gram negative bacteria, used mainly in the treatment of urinary tract infections, pulmonary tract, prostate gland, bone and bone marrow infections. Ciprofloxacin is also known for its in vitro anticancer properties. Several reports describe anti-pr...

Background and Objective: Subsequent to spinal cord injury (SCI), many pathological changes may occur that could lead to inappropriate conditions for repair. The most important of such changes include the death of neurons, cyst formation, glial scar, and ineffectiveness of monocytes. Adult stem cells and monocytes may provide new strategies to trea...

Glioma is the most common primary brain tumor. Despite many advances in treatment, all patients die within 6 to 18 months after diagnosis. In the cases of glioma, the immune system is suppressed in a local fashion. Therefore, unveiling the cellular and molecular mechanisms involved, with the aim of obtaining an appropriate new treatment is a priori...

Antibody-dependent cellular cytotoxicity (ADCC) is one means by which macrophages (as well as natural killer cells and granulocytes) elicit a cytotoxic response. This is achieved via interaction of the Fc-gamma-receptor (CD64) with the Fc portion of antibody bound to target cells. We have created a chimeric CD64 molecule that incorporates a single...

Given the failure of conventional treatments for glioblastoma, gene therapy has gained interest considerable in recent years. Gliomas are associated with a state of immunosuppression, which appears to be partially mediated by an increase in secretion of transforming growth factor- (TGF-) from glioma cells. Decorin, a small proteoglycan which can bi...