Publications by authors named "Mohammad Hossein Nasr Esfahani"

264 Publications

The role of PGS/PCL scaffolds in promoting differentiation of human embryonic stem cells into retinal ganglion cells.

Acta Biomater 2021 Mar 23. Epub 2021 Mar 23.

Queensland Micro- and Nanotechnology Centre, Griffith University, West Creek Road, Nathan QLD 4111, Australia; School of Engineering and Built Environment, Griffith University, 170 Kessels Rd, Nathan QLD 4111, Australia.

The stem cell-based retinal ganglion cells (RGCs) replacement therapy offers a potential to restore vision in progressive optic neuropathies including glaucoma by replacing degenerated RGCs and by simulating axonal regeneration. Injured optic nerve axons do not regenerate owing to the limited intrinsic capacity of the neurons and the inhibitory environment at the injury site. Polymeric tissue scaffolds are able to modulate the physical environment while providing structural support for transplanted cells, however, their application specific to the RGC generation has been far from conclusive. The successful generation of clinically safe and functional RGCs that can appropriately integrate into the hosts' retinas still remain largely unresolved. Our study reports on a process that enables generation of RGCs from human embryonic stem cells (hESCs) that is simple, straightforward and repeatable and, investigates the influence of the aligned poly(glycerol sebacate) (PGS)/poly(ε-caprolactone) (PCL) scaffold on this differentiation process. Our findings demonstrate that PGS/PCL scaffold promotes differentiation of hESCs into RGC-like cells possibly by the simulation of cell active environmental signalling and, facilitates the growth of RGCs neurites along their lengths. STATEMENT OF SIGNIFICANCE: Glaucoma can lead to the degeneration of retinal ganglion cells (RGCs), with consequential vision loss. RGCs are incapable of self-renewal, replacement of diseased RGCs with healthy cells has been a goal to restore vision in glaucoma patients. In this regard, stem cell RGC replacement therapy has been shown to improve vision in animal models of glaucoma, which could be facilitated by using tissue-engineered polymeric scaffolds. In this study, we generated homogenous stem cell-derived RGCs via a straightforward differentiation protocol and evaluated the effects of PGS/PCL scaffold on RGCs differentiation and growth of RGCs neurites. Our study contributes to the knowledge on how biomaterial scaffolds are able to support the regeneration of RGC neurites (i.e., axons or dendrites) as a part of a possible future clinical therapy for the treatment of glaucoma.
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http://dx.doi.org/10.1016/j.actbio.2021.03.036DOI Listing
March 2021

Effect of Low-Intensity Endurance Training and High-Intensity Interval Training on Sperm Quality in Male Rats with Fatty Liver.

Int J Fertil Steril 2021 Apr 11;15(2):141-147. Epub 2021 Mar 11.

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Email:

Background: We aimed to investigate the effect of low-intensity endurance training (LIET) and high-intensity interval training (HIIT) on sperm parameters, chromatin status, and oxidative stress in a rat model of non-alcoholic fatty liver disease (NAFLD).

Materials And Methods: For this experimental study, we divided 40 male Wistar rats into four groups (control, sham, HIIT and LIET) according to diet treatment and exercise training protocol. Liver triglycerides, sperm parameters, sperm lipid peroxidation (BODIPY C11 probe) and chromatin status [chromomycin A3 (CMA3)], and acridine orange [AO] staining) were assessed in these groups at the end of the study.

Results: The mean liver triglyceride values significantly improved in both the LIET and HIIT groups compared to the control and sham groups. The mean of testicular volume, sperm concentration, motility, intensity of sperm lipid peroxidation and DNA damage were similar within groups. While, the mean percentage of sperm lipid peroxidation and protamine deficiency were significantly higher in the LIET and HIIT groups compared to the control group.

Conclusion: Both LIET and HIIT in the rat NAFLD model had no adverse effects on testicular morphometric parameters, sperm concentration, motility, and DNA integrity. However, the mean sperm lipid peroxidation and protamine deficiency were significantly higher in both exercise groups. Our study suggests that exercise or antioxidant supplementation could minimise the adverse effects of oxidant by-products of exercise.
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http://dx.doi.org/10.22074/IJFS.2020.134593DOI Listing
April 2021

Fndc5 knockdown significantly decreased the expression of neurotrophins and their respective receptors during neural differentiation of mouse embryonic stem cells.

Hum Cell 2021 Mar 8. Epub 2021 Mar 8.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Ave, Azadi Square, 81746, Isfahan, Iran.

Fibronectin type III domain-containing-5 (Fndc5) is a trans-membrane protein which is involved in a variety of cellular events including neural differentiation of mouse embryonic stem cells (mESCs) as its knockdown and overexpression diminishes and facilitates this process, respectively. However, downstream targets of Fndc5 in neurogenesis are still unclear. Neurotrophins including NGF, BDNF, NT-3, and NT-4 are the primary regulators of neuronal survival, growth, differentiation, and repair. These biomolecules exert their actions through binding to two different receptor families, Trk and p75NTR. In this study, considering the fact that neurotrophins and their receptors play crucial roles in neural differentiation of ESCs, we sought to evaluate whether knockdown of Fndc5 decreased neural differentiation of mESCs by affecting the neurotrophins and their receptors expression. Results showed that at neural progenitor stage, the mRNA and protein levels of BDNF, Trk, and p75NTR receptors decreased following the Fndc5 knockdown. In mature neural cells, still, the expression of Trk and p75NTR receptors at mRNA and protein levels and BDNF and NGF expression only at protein levels showed a significant decrease in Fndc5 knockdown cells compared to control groups. Taken together, our results suggest that decreased efficiency of neural differentiation following the reduction of Fndc5 expression could be attributed to decreased levels of NGF and BDNF proteins in addition to their cognate receptors.
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http://dx.doi.org/10.1007/s13577-021-00517-zDOI Listing
March 2021

Association of heat shock protein A2 expression and sperm quality after N-acetyl-cysteine supplementation in astheno-terato-zoospermic infertile men.

Andrologia 2021 Mar 4:e14024. Epub 2021 Mar 4.

Department of Reproductive Biology, Academic Center for Education Culture and Research (ACECR), Qom, Iran.

In infertile men, reduced expression of heat shock protein A2 (HSPA2) is related to reduced sperm quality and function. The present study has aimed to investigate the effects of N-acetyl-cysteine (NAC) supplementation on expression of heat shock protein A2 (HSPA2). In this study in continuation of previous study, semen samples from 50 astheno-terato-zoospermic men who have received NAC (600 mg/day) orally for three months were evaluated for expression HSPA2 using RT-PCR, and Western blot analysis. In addition, semen samples of these individuals were assessed for sperm parameters, DNA fragmentation (TUNEL), protamine deficiency (CMA3), lipid peroxidation index (MDA) and total antioxidant capacity (TCA). All assessment was carried out before and after NAC treatment. In addition to improved sperm parameters and aforementioned functional parameters, the presented results revealed the significant increase in relative expression levels of HSPA2 was obtained after using NAC treatment (p < .05). Correlation analysis also demonstrated that HSPA2 expression is significantly related to most of the assessed parameters. NAC may directly or indecently impose its beneficial effect through increased expression of HSPA2, which plays a potential role in proper folding of element needed to counteract stress condition in infertile individuals.
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http://dx.doi.org/10.1111/and.14024DOI Listing
March 2021

Stem Cells from Human Exfoliated Deciduous Tooth Exhibit Stromal-Derived Inducing Activity and Lead to Generation of Neural Crest Cells from Human Embryonic Stem Cells.

Cell J 2021 Apr 1;23(1):140-142. Epub 2021 Mar 1.

Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

In this article which was published in Cell J, Vol 17, No 1, Spring 2015, on pages 37-48, we found that Figure 1H, Figure 2 (OTX2, row 3), and Figure 3 (row 4) had been published incorrectly. The following figures are corrected. The authors would like to apologies for any inconvenience caused.
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http://dx.doi.org/10.22074/cellj.2021.7931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944126PMC
April 2021

Assessment of Atg7 and LC3II/LC3, as The Markers of Autophagy, in Sperm of Infertile Men with Globozoospermia: A Case-Control Study.

Cell J 2021 Apr 1;23(1):70-74. Epub 2021 Mar 1.

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Email:

Objective: Assessment of relationship between LC3II/LC3 and Autophagy-related 7 (Atg7) proteins, as markers of autophagy, as well as evaluating the sperm parameters and DNA fragmentation in spermatozoa of infertile men with globozoospermia.

Materials And Methods: In this case-control study, 10 semen samples from infertile men with globozoospermia and 10 fertile individuals were collected, and the sperm parameters, sperm DNA fragmentation, and main autophagy markers (Atg7 and LC3II/LC3) were assessed according to World Health Organization (WHO) criteria, TUNEL assay, and western blot technique, respectively.

Results: The mean of sperm concentration and motility were significantly lower, while the percentage of abnormal spermatozoa and DNA fragmentation were significantly higher in infertile men with globozoospermia compared to fertile individuals (P<0.01). Unlike the relative expression of LC3II/LC3 that did not significantly differ between the two groups, the relative expression of ATG7 was significantly higher in infertile men with globozoospermia compared to fertile individuals (P <0.05). There was a significantly negative correlation between the sperm concentration (r=-0.679; P=0.005) and motility (r=-0.64; P=0.01) with the expression of ATG7, while a significantly positive association was founf between the percentage of DNA fragmentation and expression of ATG7 (0.841; P =0.018).

Conclusion: The increased expression of ATG7 and unaltered expression of LC3II/LC3 may indicate that the autophagy pathway is initiated but not completely executed in spermatozoa of individuals with globozoospermia. A significant correlation of ATG7 expression with increased sperm DNA fragmentation, reduced sperm concentration, and sperm motility may associate with the activation of a compensatory mechanism for promoting deficient spermatozoa to undergo cell death by the autophagy pathway. Therfore, this pathway could act as a double-edged sword that, at the physiological level, is involved in acrosome biogenesis, while, at the pathological level, such as globozoospermia, could act as a compensatory mechanism.
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http://dx.doi.org/10.22074/cellj.2021.7023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944124PMC
April 2021

Chitosan/polycaprolactone multilayer hydrogel: A sustained Kartogenin delivery model for cartilage regeneration.

Int J Biol Macromol 2021 Apr 18;177:589-600. Epub 2021 Feb 18.

Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address:

Cartilage regeneration using biomaterial-guided delivery systems presents improved therapeutic efficacy of the biomolecules while minimizing side effects. Here, our hypothesis was to design a multilayer scaffold of chitosan (CS) hydrogel and polycaprolactone (PCL) mat to enhance the mechanical properties, integrity and stability of CS, especially for subsequent in vivo transplantation. After conjugation of the Kartogenin (KGN) into this structure, its gradual release can promote chondrogenesis of mesenchymal stem cells (MSCs). Initially, a thin electrospun PCL layer was sandwiched between two CS hydrogels. Subsequently, KGN was superficially immobilized onto the CS matrix. The successful conjugation was confirmed by scanning electron microscopy (SEM) and infrared spectroscopy. These novel KGN-conjugated scaffolds possessed lower swelling and higher compressive modulus and showed gradual release of KGN in longer retention times. Immunofluorescent and histological staining represented more cells located in lacunae as well as more Coll2 and Sox9 positive cells on KGN-conjugated scaffolds. Gene expression analysis also revealed that SOX9, COLL2 and ACAN expression levels were higher in the presence of KGN, while COLLX expression was down-regulated, indicating a hypertrophy phenomenon with synergistic effect of TGF-β. This multilayer structure not only facilitates the effective treatment, but also provides a proper mechanical structure for cartilage engineering.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.122DOI Listing
April 2021

A nano approach towards the creation of a biointerface as stimulator of osteogenic differentiation.

Mater Sci Eng C Mater Biol Appl 2021 Jan 26;120:111746. Epub 2020 Nov 26.

Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address:

There is a great need for tissue engineering constructs with the ability to modulate stem cell behavior. The initial adhesion, growth and differentiation of stem cell are a key strategy in bone tissue engineering and it can be controlled through biomaterial-cell interface. Here we engineered a polycaprolactone/gelatin/bioactive glass (PCL/GT/BG) nanocomposite scaffold coated with Fibronectin (FN) as a potential candidate to aid the bone regeneration process by giving cells a temporary template to grow into. For this purpose, initially BG nanoparticles (nBG) of 70 ± 15 nm were synthesized, characterized and then impregnated into PCL/GT matrix to create a nanocomposite fibrous mesh. An optimized structure was selected based on fiber uniformity, diameter, and the mechanical properties. Cell adhesion, growth, and the expression of osteogenic-related genes as a result of FN tethering, through specific surface interactions, was evaluated. Furthermore, the potential of optimized nanofiberous structure as a drug delivery vehicle for the local release of therapeutic agents was studied by using amoxicillin as a model drug. The release profile revealed that around 70% of drug was released in an hour for non-crosslinked fibers (burst release) followed by a gradual release up to 72 h. The release profile was steadier for crosslinked fibers. The scaffold also showed an antibacterial effect against ubiquitous gram-positive Staphylococcus aureus. The current study provides an insight for future researchers who aim to create nanocomposite materials as multifunctional scaffolds for bone tissue engineering applications.
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http://dx.doi.org/10.1016/j.msec.2020.111746DOI Listing
January 2021

Increased expression of MUSASHI1 in epithelial breast cancer cells is due to down regulation of miR-125b.

BMC Mol Cell Biol 2021 Feb 4;22(1):10. Epub 2021 Feb 4.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Ave., Azadi Square, Isfahan, P.O. Code 81746, Iran.

Background: Musashi1 (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer. The change in expression of MSI1 has a role in solid tumor progression. There are different factors that regulate MSI1 expression in various cancer tissues including microRNAs which are considered as one of the most important of these factors. The aim of our study is identification of the molecular cause of maximal expression of MSI1 in epithelial breast cancer cell lines.

Results: Among predicted microRNAs, miR-125b, miR-637 and miR-802 were able to significantly reduce the luciferase activity. In addition, the relative expression of these three miRNAs were measured in the cancerous cell lines that results showed a significant reduction in expression of all microRNAs. On the other hand, only the overexpression of miR-125b caused a change in the expression pattern of MSI1 in breast epithelial cancer cell lines. Accordingly, our results demonstrated that the exogenous expression of miR-125b decreased not only the MSI1 protein but also expression of epithelial markers in breast cancer cells.

Conclusions: The results of luciferase reporter assay showed that MSI1 is a direct target for miR-125b in epithelial breast cancer cells. Moreover, higher amount of MSI1 in those cell lines seems due to the reduced amount of miR-125b, which is responsible for epithelial features of those kinds of cancer cells. Therefore, the modulation of miR-125b may be a potential approach to help to combat against epithelial breast tumors.
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http://dx.doi.org/10.1186/s12860-021-00348-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863248PMC
February 2021

Qur'anic Views on Human Cloning (I): Doctrinal and Theological Evidences.

Int J Fertil Steril 2021 Jan 19;15(1):73-79. Epub 2021 Jan 19.

Department of Qur'an and Hadith Sciences, Shahed University, Tehran, Iran.

Background: Human cloning is a recent occurrence that is not confined to bio-issues; rather, it has provoked numerous questions worldwide and presented scientific and religious challenges. These series of articles aim to examine the proposed approaches and analyze the aspects of human cloning in terms of tenets, morals, jurisprudence, and laws. In this paper, we analyze the ideological and theological evidences, regardless of scientific, ethical and legal problems that exist in the reproduction method.

Materials And Methods: We used a descriptive-analytical method to consider the challenges of human cloning according to the "system of Divine creativity" and "the will of God", as well as the "pairing system" and "diversity in nature" with emphasis on the Holy Qur'an and Qur'anic commentaries.

Results: According to the Qur'an, although any type of physical changes and retouching of the human body are forbidden, the alteration of God's creation may not prove the prohibition of cloning. Cloning is not contradictory to the principle, precedent, and rule of coupling, and it may be one of the hidden precedents of creation. Therefore, not only does a clone not contradict the precedent of the variety of men, but this variety is a sign for men and not a precedent predominated over the order of nature.

Conclusion: It is proven that cloning does not give life; instead, it utilizes the life bestowed by God. This technique does not contradict the precedents of existence. It is a way to discover some precedents of God and is under the order of cause and effect of the world. Cloning is not considered as a challenge to human beliefs, nor is it a change in Divine creation. Moreover, cloning does not contradict the theological teachings and concepts of the Holy Qur'an and Shiite Muslims.
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http://dx.doi.org/10.22074/ijfs.2020.134415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838753PMC
January 2021

The Effect of Recombinant Human Follicle-Stimulating Hormone on Sperm Quality, Chromatin Status and Clinical Outcomes of Infertile Oligozoospermic Men Candidate for Intracytoplasmic Sperm Injection: A Randomized Clinical Trial.

Int J Fertil Steril 2021 Jan 19;15(1):1-7. Epub 2021 Jan 19.

Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Background: Follicle-stimulating hormone (FSH) plays a crucial role in spermatogenesis; in this study, we assessed the effect of recombinant human FSH (rhFSH) on sperm parameters, chromatin status and clinical outcomes of infertile oligozoospermic men candidates for intracytoplasmic sperm injection (ICSI).

Materials And Methods: This interventional randomized clinical trials (IRCT) included 40 infertile oligozoospermic men undergoing ICSI. These individuals were randomized into two groups: 20 men received rhFSH drug for three months and the other 20 men who did not receive rhFSH drug were considered the control group. Before and 3 months after treatment initiation, sperm parameters (using computer-assisted semen analysis) and chromatin status [using chromomycin A3, aniline blue, and sperm chromatin dispersion (SCD) tests] were assessed in these individuals. Furthermore, hormonal profile was assessed using enzyme-linked immunosorbent assay (ELISA). Clinical outcomes of ICSI were also compared between the two groups.

Results: The rhFSH treated group showed a significant increase in the level of FSH, luteinizing hormone (LH), testosterone (T) and prolactin (PRL), as well as significant improvements in sperm parameters compared to the control group. Also, after administration of rhFSH, there was asignificant reduction in the percentage of sperm DNA damage, protamine deficiency and chromatin immaturity, while such a reduction in these parameters was not observed in the control group. Moreover, the percentage of embryos with grade Aquality, was significantly higher in the rhFSH group compared to the control group. The pregnancy rate in the rhFSH group was higher than the control group but the difference was insignificant.

Conclusion: Administration of rhFSH improves sperm quality in infertile oligozoospermic men and results in higher rates of good quality embryos post-ICSI (Registration number: IRCT20170923036334N2).
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http://dx.doi.org/10.22074/ijfs.2021.6210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838760PMC
January 2021

A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.

Nutr Metab (Lond) 2021 Jan 19;18(1):14. Epub 2021 Jan 19.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Avenue, Azadi Sq., Isfahan, 81746-73441, Iran.

Background: SPTC is a mix of four herbal components (Salvia officinalis, Panax ginseng, Trigonella foenum-graeceum, and Cinnamomum zeylanicum) which might be prevented the development of AGE rich diet-induced diabetic complication and liver injury through activated the nuclear factor erythroid-2-related-factor-2 (Nrf2) pathway. Nrf2, as a master regulator of antioxidant response elements by activating cytoprotective genes expression, is decreased oxidative stress that associated with hyperglycemia and increases insulin sensitivity. the aim of this study was to assess whether the combination therapy of SPTC along with exercise or metformin moderate oxidative stress related liver injurie with more favorable effects in the treatment of AGE rich diet-induced type 2 diabetic mice.

Methods: We induced diabetes in C57BL/6 mice by AGE using a diet supplementation and limitation of physical activity. After 16 weeks of intervention, AGE fed mice were compared to control mice. Diabetic mice were assigned into seven experimental groups (each group; n = 5): diabetic mice, diabetic mice treated with SPTC (130 mg/kg), diabetic mice treated with Salvia Officinalis (65 mg/kg), diabetic mice treated with metformin (300 mg/kg), diabetic mice with endurance exercise training, diabetic mice treated with SPTC + metformin (130/300 mg/kg), diabetic mice treated with SPTC + exercise training.

Results: SPTC + exercise and SPTC + metformin reduced diabetic complications like gain weight, water and calorie intake, blood glucose, insulin, and GLUT4 content more efficiently than each treatment. These combinations improved oxidative stress hemostasis by activating the Nrf2 signaling pathway and attenuating keap1 protein more significantly.

Conclusion: Eventually, combined treatment of SPTC with exercise or metformin as a novel approach had more beneficial effects to prevent the development of diabetes and oxidative stress associated with hyperglycemia.
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http://dx.doi.org/10.1186/s12986-021-00543-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816367PMC
January 2021

Electroconductive Graphene-Containing Polymeric Patch: A Promising Platform for Future Cardiac Repair.

ACS Biomater Sci Eng 2020 07 3;6(7):4214-4224. Epub 2020 Jun 3.

Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Myocardial infarction (MI) is one of the leading causes of death worldwide. The complications associated with MI can lead to the formation of nonconductive fibrous scar tissues. Despite the great improvement in electroconductive biomaterials to increase the physiological function of bio-engineered cardiac tissues in vivo, there are still several challenges in creating a suitable scaffold with appropriate mechanical and electrical properties. In the current study, a highly hydrophilic fibrous scaffold composed of polycaprolactone/chitosan/polypyrrole (PCP) and combined with functionalized graphene, to provide superior conductivity and a stronger mechanical cardiopatch, is presented. The PCP/graphene (PCPG) patches were optimized to show mechanical and conductive properties close to the native myocardium. Also, the engineered patches showed strong capability as a drug delivery system. Heparin, an anticoagulant drug, was loaded within the fibrous patches, and the adsorption of the bovine serum albumin (BSA) protein was evaluated. The optimized cardiopatch shows great potential to be used to provide mechanical support and restore electromechanical coupling at the site of MI to maintain a normal cardiac function.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00266DOI Listing
July 2020

Ferulago angulata extract improves the quality of buck spermatozoa post-thaw and counteracts the harmful effects of diazinon and lead.

Cryobiology 2021 Feb 16;98:17-24. Epub 2021 Jan 16.

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

During cryopreservation, spermatozoa are exposed to chemical or physical stress that has adverse effects on the quality of mammalian spermatozoa. Recently, much attention has been paid to environmental contaminants (ECs) in livestock, because of their detrimental effects on livestock productivity and fertility. ECs like diazinon (DZN) and lead acetate (LA) are considered ubiquitous and induced oxidative stress, which decreases spermatozoa quality. Since Ferulago angulata extract (FAE) has antioxidant properties, the present study investigated the effect of FAE supplementation in a freezing extender, in the presence or absence of DZN + LA, during cryopreservation, on the quality and fertility ability of buck spermatozoa after thawing. Pooled ejaculates were diluted with a freezing extender and supplemented with FAE (0.002%, w/v) in the presence or absence of DZN (100 μM) + LA (12.5 μM). Post-thaw spermatozoa parameters, ROS production, fertilization ability, and developmental competence of oocytes inseminated with FAE/DZN + LA treated spermatozoa were calculated. The results demonstrated that FAE improves cryopreserved spermatozoa motility, viability, membrane integrity, fertilizability, and developmental competence, and reduced spermatozoa ROS production in the presence or absence of DZN + LA. Besides, FAE significantly restored the adverse effects of DZN + LA exposure during cryopreservation on inner cell mass (ICM) count, trophectoderm (TE) cell count, total cell number (TCN), and the ratio between ICM to TCN. In conclusion, FAE on its own resulted in an improvement in the buck spermatozoa's quality and fertility. Therefore, the addition of FAE, as a natural antioxidant to buck semen extender, can increase spermatozoa cryotolerance and post-thaw resistance even when exposed to ECs.
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http://dx.doi.org/10.1016/j.cryobiol.2021.01.008DOI Listing
February 2021

Full small molecule conversion of human fibroblasts to neuroectodermal cells via a cocktail of Dorsomorphin and Trichostatin A.

Regen Ther 2020 Dec 15;15:44-52. Epub 2020 Jun 15.

Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

A revolutionary new approach to produce efficient cells is to induce transdifferentiation to make it conventional in therapeutic strategies. In this paper, we describe a brief cocktail of small molecules including Dorsomorphin (DSM) and Trichostatin A (TSA) to produce safe neuroectodermal cells as a resource to produce various types of nervous system cells for a safe cytotherapy. Furthermore, in order to optimize this strategy, we implemented a cocktail of neurotrophic factors to enhance the viability of the cell. This modification was accompanied by pretreatment of the culture dishes with a combination of poly-l-ornithine and laminin and fibronectin. In order to decrease the length of protocol and transdifferentiation variation concomitantly, TSA was utilized as an epigenetic modulator. Finally, this improved protocol mediated neuroectodermal conversion of human fibroblasts within 12 days with an average efficiency of 24%, promising a fast strategy to produce neuroectodermal cells applicable for therapeutic purposes in neural damages. Here we induce neural cells by a cocktail consists of two small molecules of DSM and TSA. Our protocol is a 12 day protocol with the efficiency of 24% which is a more efficient one in comparison to previous protocols inducing neural cells. Consequently, our protocol shortens the path of in vitro and preclinical studies in the field of neural conversion and neuroregeneration.
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http://dx.doi.org/10.1016/j.reth.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770348PMC
December 2020

Do neprilysin inhibitors walk the line? Heart ameliorative but brain threatening!

Eur J Pharmacol 2021 Mar 8;894:173851. Epub 2021 Jan 8.

Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Sacubitril/valsartan (Entresto™; LCZ696) is the first angiotensin receptor-neprilysin inhibitor (ARNI) drug approved by the US and EU for heart failure (HF) and especially recommended for hypertensive HF (HHF). Sacubitril inhibits the enzyme neprilysin (NEP) which produces both beneficial and adverse effects in the human body. While LCZ696 causes beneficial cardiovascular effects, it may induce memory and cognitive dysfunction, or even exacerbate Alzheimer's disease (AD). This article reviewed data reported by experimental and clinical studies that examined NEP inhibitors and their dementia-related side effects. Based on the literature, LCZ696 increases the risk of memory and cognitive dysfunctions, and clinical trials failed to show compelling evidence for LCZ696 safety for the brain. Together, it was concluded that more experimental and clinical studies with particular focus on LCZ696 side effects on β-amyloid (Aβ) degradation are needed to assess LCZ696 safety for the cognitive function, especially in case of long-term administration.
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http://dx.doi.org/10.1016/j.ejphar.2021.173851DOI Listing
March 2021

ZIF-8 Modified Polypropylene Membrane: A Biomimetic Cell Culture Platform with a View to the Improvement of Guided Bone Regeneration.

Int J Nanomedicine 2020 9;15:10029-10043. Epub 2020 Dec 9.

School of Chemical Engineering, University of Queensland, Brisbane, QLD, 4072, Australia.

Purpose: Despite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal-organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility.

Results: In situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like , and . Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer.

Conclusion: Hence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering.
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http://dx.doi.org/10.2147/IJN.S269169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737945PMC
December 2020

Effect of rosiglitazone on developmental competence of mouse embryos treated with lipopolysaccharide.

Theriogenology 2021 Feb 30;161:57-64. Epub 2020 Nov 30.

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address:

Lipopolysaccharide (LPS) significantly reduces pre- and post-implantation developmental competence of embryos. One of the reason of this effect could be a consequence of TLR4-mediated inflammation. In this study, we assessed the anti-inflammatory effect of peroxisome proliferator activated receptor γ (PPAR γ) agonist, rosiglitazone (RGZ), in LPS-treated mouse embryos. Initially, the optimal doses of LPS, RGZ and GW9662 (a potent and selective PPARγ antagonist) were determined by treating the mouse zygotes up to blastocyst stage and assessment of compaction and blastocyst rates. Quantitative PCR was used to assess the mRNA expression of inflammatory cytokines. Immunostaining was used to study the translocation of PPARγ in blastocysts. Finally, the blastocysts were transferred to surrogate mouse to determine the post-implantation developmental competence. 0.0625 mg/mL of LPS significantly reduced the developmental competency by around 50% compared to control group. 10 μM of RGZ significantly ameliorated the toxic effect of LPS, which was also significantly reversed by 1.25 μM GW9662. Through immunostaining, it was shown that LPS could prevent the translocation of PPARγ to nucleus; and translocation was facilitated by RGZ and this effect was reversed by GW9662. A similar effect was also observed for the mRNA expression of inflammatory cytokines (Il-1β and Il-6). LPS significantly increased the expression of these cytokines, while RGZ significantly reduced their expression, which was also significantly reversed by GW9662. It was also shown that embryos exposed to LPS had significantly reduced post implantation developmental competence which was considerably improved by treatment with RGZ. In conclusion, these data may have clinical implications for ameliorating the adverse effects of LPS in dairy farming and infertility treatment.
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http://dx.doi.org/10.1016/j.theriogenology.2020.11.022DOI Listing
February 2021

A compound downregulation of SRRM2 and miR-27a-3p with upregulation of miR-27b-3p in PBMCs of Parkinson's patients is associated with the early stage onset of disease.

PLoS One 2020 10;15(11):e0240855. Epub 2020 Nov 10.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Parkinson's disease (PD) is diagnosed when motor symptoms emerges, which almost 70% of dopamine neurons are lost. Therefore, early diagnosis of PD is crucial to prevent the progress of disease. Blood-based biomarkers, which are minimally invasive, potentially used for diagnosis of PD, including miRNAs. The aim of this study was to assess whether SRRM2 and miR-27a/b-3p could act as early diagnostic biomarkers for PD. Total RNAs from PBMCs of 30 PD's patients and 14 healthy age and gender matched subjects was extracted. The expression levels of respective genes were assessed. Data were presented applying a two-tailed unpaired t-test and one-way ANOVA. We observed significant down-regulation of SRRM2 (p = 0.0002) and miR-27a-3p (p = 0.0001), and up-regulation of miR-27b-3p (p = 0.02) in PBMCs of Parkinson's patients. Down-regulation of miR-27a-3p is associated with increasing disease severity, whereas the up-regulation of miR-27b-3p was observed mostly at HY-1 and disease duration between 3-5 years. There was a negative correlation between SRRM2 and miR-27b-3p expressions, and miR-27a-3p positively was correlated with miR-27b-3p. Based on functional enrichment analysis, SRRM2 and miR-27a/b-3p acted on common functional pathways. miR-27a/b-3p could potentially predict the progression and severity of PD. Although both miRs had no similarity on expression, a positive correlation between both miRs was identified, supporting their potential role as biomarkers in clinical PD stages. Of note that SRRM2 and miR-27a-3p were able to distinguish PD patients from healthy individuals. Functional analysis of the similarity between genes associated with SRRM2 and miR-27a/b-3p indicates common functional pathways and their dysfunction correlates with molecular etiopathology mechanisms of PD onset.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240855PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654768PMC
December 2020

Design of hydrogel-based scaffolds for the treatment of spinal cord injuries.

J Mater Chem B 2020 12 6;8(47):10712-10738. Epub 2020 Nov 6.

Department of Cellular Biotechnology Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Spinal cord injury (SCI) is a traumatic lesion that diminishes sensory and/or motor neuronal functionality, directly affecting the quality of the patient's life. Due to the central nervous system's (CNS) inhibitory microenvironment that presents challenges in neuron repair and regeneration, tissue engineering strategies have received significant attention to improve the quality of a patient's life. In this regard, hydrogels are attractive SC scaffolds as they can provide not only an adjustable physiologically native-like microenvironment but also an appropriate matrix for cell delivery, drug delivery, and other bioactive molecule delivery at the lesion site. This systematic review characterizes the widely used biomaterials including natural polymers; protein- and polysaccharide-based synthetic polymers; methacrylate- and polyethylene glycol-based, and self-assembling (SA) peptides. In addition, synthesis routes of hydrogels are investigated. This review is complemented by the discussion of the various techniques utilized for hydrogel scaffold designs with their in vitro and in vivo outcomes and clinical trials. The existing challenges and opportunities for SC hydrogel scaffolds are mentioned towards the end of this review.
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http://dx.doi.org/10.1039/d0tb01842bDOI Listing
December 2020

Upregulation of miR-9 and miR-193b over human Th17 cell differentiation.

Mol Genet Genomic Med 2020 12 31;8(12):e1538. Epub 2020 Oct 31.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Background: Th17 cells are a newly discovered subset of CD4 T cells known as key participants in various immune responses and inflammatory conditions including autoimmune diseases. Mi(cro)RNAs are a family of non-coding RNAs that regulate numerous critical immune functions. Immuno-miRNAs modulate cell biological processes in T cells, such as differentiation and function of Th17 cells. The aim of the present study is to investigate the expression of miR-9-5p, miR-193b-3p, and autoimmunity-related genes during human Th17 cells differentiation.

Methods: Human naïve CD4 T cells were purified from peripheral blood mononuclear cells (PBMCs) by magnetic cell sorting system (MACS) and their purity was checked by flow-cytometric analysis. Naïve CD4 T cells were cultured under Th17-polarizing condition for 6 days. IL- 17 secretion was determined by means of enzyme-linked immunosorbent assay (ELISA). Next, the expression levels of miRNAs and putative targets genes were assessed by qRT-PCR at different time points of differentiation.

Results: Our result showed dramatic downregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes during human Th17 differentiation. Polarization also had a significant inducible effect on the expression of miR-9 and miR-193b over differentiation of human Th17 cells. According to our results, miR-9-5p and miR-193b-3p may contribute to Th17 differentiation probably by inhibiting the expression of negative regulators of Th17 differentiation.

Conclusion: This study confirmed deregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes in Th17 differentiation process and introduced miR-9 and miR-193b as Th17 cell-associated miRNAs, making them good candidates for further investigations.
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http://dx.doi.org/10.1002/mgg3.1538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767567PMC
December 2020

Receptor for Advanced Glycation End Products Acts as a Fuel to Colorectal Cancer Development.

Front Oncol 2020 29;10:552283. Epub 2020 Sep 29.

Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, Academic Center for Education, Culture and Reasearch (ACECR), Isfahan, Iran.

Receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein taken in diverse chronic inflammatory conditions. RAGE behaves as a pattern recognition receptor, which binds and is engaged in the cellular response to a variety of damage-associated molecular pattern molecules, as well as HMGB1, S100 proteins, and AGEs (advanced glycation end-products). The RAGE activation turns out to a formation of numerous intracellular signaling mechanisms, resulting in the progression and prolongation of colorectal carcinoma (CRC). The RAGE expression correlates well with the survival of colon cancer cells. RAGE is involved in the tumorigenesis, which increases and develops well in the stressed tumor microenvironment. In this review, we summarized downstream signaling cascade activated by the multiligand activation of RAGE, as well as RAGE ligands and their sources, clinical studies, and tumor markers related to RAGE particularly in the inflammatory tumor microenvironment in CRC. Furthermore, the role of RAGE signaling pathway in CRC patients with diabetic mellitus is investigated. RAGE has been reported to drive assorted signaling pathways, including activator protein 1, nuclear factor-κB, signal transducer and activator of transcription 3, SMAD family member 4 (Smad4), mitogen-activated protein kinases, mammalian target of rapamycin, phosphoinositide 3-kinases, reticular activating system, Wnt/β-catenin pathway, and Glycogen synthase kinase 3β, and even microRNAs.
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http://dx.doi.org/10.3389/fonc.2020.552283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551201PMC
September 2020

The Effect of N-Acetyl-Cysteine on Antioxidant Gene Expression in Asthenoteratozoospermia Men: A Clinical Trial Study.

Int J Fertil Steril 2020 Oct 12;14(3):171-175. Epub 2020 Oct 12.

Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic Address:

Background: One of the important factor associated with male infertility is high production of reactive oxygen species (ROS). The main function of Nuclear factor erythroid 2-related factor 2 () is to activate the cellular antioxidant response by inducing the transcription of a wide array of genes that can combat the harmful effects of factors such as oxidative stress. The purpose of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC), as an antioxidant drug, on NRF2 Gene Expression in Asthenoteratozoospermia Men.

Materials And Methods: In this randomized, blinded clinical trial study, included 50 infertile men with asthenoteratozoospermia, who received NAC (600 mg, three times daily). Sperm parameters analyzed according to the world health organization (WHO; 2010). Sperm DNA fragmentation, relative expression, and seminal plasma level of antioxidant enzymes were measured by TUNEL assay, reverse transcription polymerase chain reaction (RT-PCR) and ELISA test, respectively.

Results: After NAC treatment, findings showed a significant increase in sperm concentration and motility compared to pre-treatment status, whereas the percentage of abnormal morphology and DNA fragmentation was significantly decreased (P<0.05). A significant improvement in expression of gene and antioxidant enzyme levels were observed compared to pre-treatment by NAC (P<0.05). Significant correlations were observed between NRF2 mRNA expression level, specific sperm parameters and level of antioxidant enzymes (P<0.05).

Conclusion: The results demonstrated that NAC oral supplementation protected against oxidative stress by enhancing NRF2 expression. This could improve semen parameters quality parameters in asthenoteratozoospermia men (Registration number: IRCT20170830035998N4).
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http://dx.doi.org/10.22074/ijfs.2020.44411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604699PMC
October 2020

Transcript Isoforms of SLC7A11-AS1 Are Associated With Varicocele-Related Male Infertility.

Front Genet 2020 11;11:1015. Epub 2020 Sep 11.

Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, Academic Center for Education, Culture and Research (ACECR), Isfahan, Iran.

Oxidative stress is one of the crucial mediators of varicocele-related male infertility. Recently, roles of long noncoding RNAs (lncRNAs) in oxidative stress have begun to emerge, however, little is known about their role in male infertility. The aim of this study was to determine the role of lncRNA SLC7A11-AS1 in varicocele-related male infertility. Through a high-throughput bioinformatics investigation, we predicted that lncRNA SLC7A11-AS1 might be involved in this type of infertility. The reactive oxygen species (ROS) levels and expression levels of SLC7A11-AS1 isoforms were evaluated in ejaculated spermatozoa of 25 infertile men with varicocele and 17 fertile individuals as control. Isoform 6 of SLC7A11-AS1 that showed a significant elevation in infertile men with varicocele relative to the fertile group was overexpressed in testicular-derived carcinoma cell lines (NT2 and NCCIT) followed by assessment of ROS, glutathione (GSH), lipid peroxidation, and cell viability. Overexpression of SLC7A11-AS1 isoform 6 in NT2 and NCCIT cell lines resulted in a significant downregulation of SLC7A11 gene expression, which consequently decreased GSH levels and concomitantly increased ROS levels and enhanced lipid peroxidation, which jeopardized cell survival and promoted cell death. Our finding revealed a potential role of oxidative-related lncRNAs in the pathophysiology of male infertility associated with varicocele.
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http://dx.doi.org/10.3389/fgene.2020.01015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516207PMC
September 2020

Capsaicin improves sperm quality in rats with experimental varicocele.

Andrologia 2020 Dec 20;52(11):e13762. Epub 2020 Aug 20.

Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Capsaicin is the main capsaicinoid in chilli peppers that have numerous biological and pharmaceutical roles in the body such as antioxidant, anti-inflammatory, anticarcinogenic, analgesic, counterirritant and antiarthritic properties. Numerous studies have shown increased oxidative stress in men with varicocele that is caused by dilation of the spermatic vein and increase of testicular temperature. Therefore, we aimed to assess the effect of Capsaicin on sperm parameters in rats with experimental varicocele. At first, we induced varicocele in 30 Wistar rats and, verify varicocele model only in 10 rats by assessment of sperm parameters, oxidative stress, DNA damage and persistent histone after 2 months. Of the remaining 20 varicocelised rats, half of them were treated with 2.5 mg/kg Capsaicin for two months and the other half served as control. Then, sperm tests were assessed, and the results showed that Capsaicin can restore the mean of sperm oxidative stress (38.78 ± 3.75 versus 58.37 ± 4.34; p < .05), sperm concentration (60.14 ± 7.66 versus 34.87 ± 5.78; p < .05) and motility (62.43 ± 3.10 versus 41.22 ± 5.11; p < .05) in varicocelised rats treated with Capsaicin compared to varicocelised rats that were not treat. Therefore, Capsaicin possibly with reduction of oxidative stress level could improve mean of sperm concentration and motility in varicocele condition.
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http://dx.doi.org/10.1111/and.13762DOI Listing
December 2020

FeO/Bioactive glass nanostructure: A promising therapeutic platform for osteosarcoma treatment.

Biomed Mater 2020 Jul 21. Epub 2020 Jul 21.

Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran, Isfahan, IRAN, ISLAMIC REPUBLIC OF.

An effective strategy of hyperthermia-chemotherapy-regeneration for bone-related cancer treatments is presented. For this purpose, a new approach of magnetic particles (MPs) encapsulated in bioactive glass (BG) structure, with anti-cancer activity, is evaluated. MPs are initially synthesized using co-precipitation method and then embedded into BG structure through sol-gel synthesis process. Results confirmed the formation of a crystalline and pure MP structure. MP-BG particles were found to be bioactive by forming a hydroxyapatite layer on their surface. The hyperthermia application of MP-BG system was also studied. It was found that the particles reach a temperature of 42 °C in an alternating magnetic field. Doxorubicin (DOX), a widely used anticancer drug, was loaded in MP-BG. To enhance loading efficiency, BG was surface modified to create NH2 groups on the surface. The encapsulation and release of DOX was studied over 48 h. In vitro tests were performed using human osteosarcoma cell line (MG63). The results demonstrated the non-cytotoxic nature of MP and MP-BG tested at various concentrations. DOX release from MP-BG resulted in decreased MG63 viability. Also, fluorescence microscopy visualization confirmed the intracellular uptake of MP-BG particles and the release of DOX. These results indicate that our suggested strategy of combined hyperthermia-chemotherapy-regeneration using MP-BG structure represents a powerful approach in cancer treatment and tissue regeneration.
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http://dx.doi.org/10.1088/1748-605X/aba7d5DOI Listing
July 2020

Effect of Vitamin D3 on Mitochondrial Biogenesis in Granulosa Cells Derived from Polycystic Ovary Syndrome.

Int J Fertil Steril 2020 Jul 15;14(2):143-149. Epub 2020 Jul 15.

Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic Address:

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder diagnosed by anovulation hyperandrogenism. Hyperandrogenism increases apoptosis, which will eventually disturb follicular growth in PCOS patients. Since mitochondria regulate apoptosis, they might be affected by high incidence of follicular atresia. This may cause infertility. Since vitamin D3 has been shown to improve the PCOS symptoms, the aim of study was to investigate the effects vitamin D3 on copy number, mitochondrial biogenesis, and membrane integrity of granulosa cells in a PCOS-induced mouse model.

Materials And Methods: In this experimental study, the PCOS mouse model was induced by dehydroepiandrosterone (DHEA). Granulosa cells after identification by follicle-stimulating hormone receptor (FSHR) were cultured in three groups: 1. granulosa cells treated with vitamin D3 (100 nM for 24 hours), 2. granulosa cells without any treatments, 3. Non-PCOS granulosa cells (control group). Mitochondrial biogenesis gene (TFAM) expression was compared between different groups using real-time PCR. copy number was also investigated by qPCR. The mitochondrial structure was evaluated by transmission electron microscopy (TEM). Hormonal levels were measured by an enzymelinked immunosorbent assay (ELISA) kit.

Results: The numbers of pre-antral and antral follicles increased in PCOS group in comparison with the non-PCOS group. Mitochondrial biogenesis genes were downregulated in granulosa cells of PCOS mice when compared to the non-PCOS granulosa cells. However, treatment with vitamin D3 increased expression levels of these genes compared to PCOS granulosa cells with no treatments. Most of the mitochondria in the PCOS group were spherical with almost no cristae. Our results showed that in the PCOS group treated with vitamin D3, the copy number increased significantly in comparison to PCOS granulosa cells with no treatments.

Conclusion: According to this study, we can conclude, vitamin D3 improves mitochondrial biogenesis and membrane integrity, mtDNA copy number in granulosa cells of PCOS mice which might improve follicular development and subsequently oocyte quality.
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http://dx.doi.org/10.22074/ijfs.2020.6077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382678PMC
July 2020