Publications by authors named "Akram Sarmadi"

7 Publications

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Calcitonin-loaded octamaleimic acid-silsesquioxane nanoparticles in hydrogel scaffold support osteoinductivity in bone regeneration.

Pharm Dev Technol 2021 Feb 27;26(2):220-232. Epub 2020 Dec 27.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Novel osteoinductive scaffolds fabricated using the benefits of tissue engineering techniques accompanied by utilizing drugs can accelerate bone regeneration. The purpose of this study was to load salmon calcitonin (sCT) in octamaleimic acid-silsesquioxane (OMA-POSS) nanoparticles and enrich the hydrogel scaffold based on hydroxyapatite, Gelrite® and platelet-rich plasma (PRP) for use in bone tissue engineering. The loading efficiency, release percentage, particle size and zeta potential of the nanoparticles were evaluated. The proliferation of seeded MG-63 osteoblast cells on the designed scaffold, its cytotoxicity and osteo-conductivity were studied by alkaline phosphatase measurement and Alizarin red staining. The expression of cellular osteogenic markers such as collagen 1 (COL1A1), osteocalcin (BGLAP) and osteopontin (SPP1) was examined using reverse transcription polymerase chain reaction. The results revealed that the particle size of the nanoparticles varied between 94.2 and 199.2 nm and their negative surface charge increased after drug conjugation. The osteoblast cell proliferation and calcium granule production in the optimum formulation were significantly higher in comparison with the control group ( < 0.05). Osteogenic markers increased significantly after a specific number of days of cell culture compared to the control group ( < 0.05). The results also showed the potential of the designed scaffold in bone tissue engineering.
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http://dx.doi.org/10.1080/10837450.2020.1858318DOI Listing
February 2021

Molecular Genetic Study in a Cohort of Iranian Families Suspected to Maturity-Onset Diabetes of the Young, Reveals a Recurrent Mutation and a High-Risk Variant in the Gene.

Adv Biomed Res 2020 27;9:25. Epub 2020 Jun 27.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Diabetes mellitus (DM) is a group of metabolic disorders in the body, accompanied with increasing blood sugar levels. Diabetes is classified into three groups: Type 1 DM (T1DM), Type 2 DM (T2DM), and monogenic diabetes. Maturity-onset diabetes of the young (MODY) is a monogenic diabetes that is frequently mistaken for T1D or T2D. The aim of this study was to diagnose MODY and its subtype frequency in a diabetic population in Iran.

Materials And Methods: In this study among ten diabetic families that were highly suspected to MODY by nongenetic biomarkers and without any pathogenic mutation in and genes, two patients from two unrelated families were examined via whole-exome sequencing (WES) in order to detect the causative gene of diabetes. Co-segregation analysis of the identified variant was performed using Sanger sequencing.

Results: In this study, no pathogenic variant was found in and genes (MODY2 and MODY3), while these two types of MODY were introduced as the most frequent in other studies. By using WES, a pathogenic variant (p.I488T) was found in one of the patients in gene causing MODY8 that its frequency is very rare in other studied populations. A high-risk variant associated with diabetes was found in another patient.

Conclusion: WES was applied in this study to reveal the cause of MODY in 1 family. This pathogenic mutation was previously reported as a disease causing mutation.
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http://dx.doi.org/10.4103/abr.abr_18_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532821PMC
June 2020

Whole exome sequencing identifies novel compound heterozygous pathogenic variants in the MYO15A gene leading to autosomal recessive non-syndromic hearing loss.

Mol Biol Rep 2020 Jul 4;47(7):5355-5364. Epub 2020 Jul 4.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease, for which more than 70 genes have been identified. MYO15A mutations have been reported to cause congenital severe-to-profound HL. In this study, we applied the whole exome sequencing (WES) to find the cause of HL in an Iranian family. A proband from an Iranian non-consanguineous family with hearing impaired parents, was examined via WES, after excluding GJB2 mutations as the most common ARNSHL gene via Sanger sequencing. Co-segregation analysis of the candidate variant was done in the family members. Interpretation of variants was according to the American College of Medical Genetics and Genomics (ACMG) guidelines. WES results showed novel compound heterozygous variants (p.Arg1507Ter and p.Val2815Valfs*10) in the MYO15A gene. These two variants, residing in highly conserved regions, were found to be co-segregating in the family and fulfill the criteria of being categorized as pathogenic, according to the ACMG guidelines. Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL in a patient with ARNSHL, as an example of an extremely heterogeneous disease. In agreement with previous studies, MYO15A is regarded to be important in causing HL in Iran.
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http://dx.doi.org/10.1007/s11033-020-05618-wDOI Listing
July 2020

Injectable gellan gum/lignocellulose nanofibrils hydrogels enriched with melatonin loaded forsterite nanoparticles for cartilage tissue engineering: Fabrication, characterization and cell culture studies.

Mater Sci Eng C Mater Biol Appl 2020 Oct 26;115:111114. Epub 2020 May 26.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Injectable hydrogels based on natural polysaccharides have attracted considerable attention in cartilage tissue engineering, especially those reinforced with mineral nanofilers carrying drug molecules. Here, a novel injectable hydrogel based on gellan gum (GG)/lignocellulose nanofibrils (LG) composite enriched with melatonin (MEL) loaded forsterite (FS) nanoparticles (FS-MEL) was developed to yield enhanced mechanical and biological properties of the hydrogels. Gelation time and temperature were determined for different hydrogel formulation containing 1-5 w/v% LG and 0.1-0.3 w/v% FS-MEL. The injectability test proved the ease of injection of the developed hydrogels. Degradation rate and swelling degree of developed hydrogel were evaluated to determine the effect of LG and FS on hydrogel behaviour. Results of mechanical characterization showed that the compressive modulus and strength of GG hydrogels were improved by incorporation of LG and FS. The results of MEL release study in PBS revealed that MEL showed more sustained release from the hydrogel compared to FS nanoparticles. Cell-hydrogels interaction was evaluated by culturing chondrocyte cells. Results exhibited higher cell adhesion, proliferation and gene expression on GG/LG/FS-MEL hydrogel compared to GG/LG and GG/LG/FS, which can be attributed to the synergic effect of FS and MEL. Overall results demonstrated that the developed GG/LG/FS-MEL hydrogels can be offered as promising materials for cartilage regeneration applications.
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http://dx.doi.org/10.1016/j.msec.2020.111114DOI Listing
October 2020

A novel pathogenic variant in the LRTOMT gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

BMC Med Genet 2020 06 9;21(1):127. Epub 2020 Jun 9.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Hearing loss (HL) is the most common sensorineural disorder with high phenotypic and genotypic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) constitutes a major share of HL cases. In the present study, Whole exome sequencing (WES) was applied to investigate the underlying etiology of HL in an Iranian patient with ARNSHL.

Methods: A proband from an Iranian consanguineous family was examined via WES, following GJB2 sequencing. WES was utilized to find possible genetic etiology of the disease. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Co-segregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.

Results: WES results showed a novel frameshift (16 bp deletion) variant (p.Ala170Alafs*20) in the LRTOMT gene. This variant, which resides in exon 6, was found to be co-segregating in the family. It fulfils the criteria set by the ACMG guidelines of being pathogenic.

Conclusion: Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL, which is a genetically heterogeneous disorder, in a patient with ARNSHL.
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http://dx.doi.org/10.1186/s12881-020-01061-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285524PMC
June 2020

Genetic Study of Hepatocyte Nuclear Factor 1 Alpha Variants in Development of Early-Onset Diabetes Type 2 and Maturity-Onset Diabetes of the Young 3 in Iran.

Adv Biomed Res 2019 23;8:55. Epub 2019 Sep 23.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous group of diabetes characterized by noninsulin-dependent, autosomal-dominant disorder with strong familial history, early age of onset, and pancreatic beta-cell dysfunction. Mutations in at least 14 different genes are responsible for various MODY subtypes. Heterozygous mutations in the hepatocyte nuclear factor 1 alpha () gene are responsible for the MODY3 subtype, which is a common subtype of MODY in different studied populations. To date, more than 450 different variants of this gene have been reported as disease causing for MODY3. This study was carried out to evaluate mutations in Iranian diabetic families fulfilling MODY criteria.

Materials And Methods: Polymerase chain reaction and Sanger sequencing were performed. All the ten exons of the gene were sequenced in ten families, followed by cosegregation analysis and evaluation. Computational protein modeling was accomplished for the identified mutation.

Results: MODY3 was confirmed in two large families by detecting a mutation (p.G253E) in coding regions of . Compound heterozygous state for two common variants in (p.I27 L and p.S487N) was detected in affected members of 5 families, and in one family, a rare benign variant in the coding sequence for Kozak sequence was detected. Two new nonpathogenic variants were found in noncoding regions of .

Conclusion: It seems that mutations are a common cause of MODY in Iranian diabetic patients. Identified common variants in heterozygous state can cause diabetes Type II in earlier ages. The role of rare variant rs3455720 is unknown, and more investigation is needed to uncover the function of this variant.
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http://dx.doi.org/10.4103/abr.abr_54_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777141PMC
September 2019

Alteration in CD8 T cell subsets in enterovirus-infected patients: An alarming factor for type 1 diabetes mellitus.

Kaohsiung J Med Sci 2018 May 20;34(5):274-280. Epub 2018 Jan 20.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Type 1 diabetes is a multi-factorial disease that can develop due to the combination of genetic and environmental factors. Viruses, particularly enteroviruses, are major environmental candidates in the pathogenesis of type 1 diabetes, even though the mechanisms of pathogenicity of these viruses and their effects on the immune system have not been understood very well yet. Previous studies show that any imbalance in the population of different lymphocyte subsets could develop autoimmune diseases. Our theory is that enteroviral infection causes an impairment in the distribution of lymphocyte subtypes and consequently results in the diabetes onset in some individuals. Therefore, in this project, we evaluated the distribution of T CD8+ lymphocytes and their subsets in type 1 diabetes patients. This study was conducted to investigate the relationship between enteroviral infection and type 1 diabetes mellitus in an Iranian population, and suggestion a predicting approach for susceptible subjects.
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http://dx.doi.org/10.1016/j.kjms.2017.12.010DOI Listing
May 2018