Cell Journal (Yakhteh)

281-290

Authors: Maryam Sadat Hosseini; Masoumeh Nouri; Morteza Zarrabi; Mohammad Javad Fatemi; Anastasia Shpichka; Peter Timashev; Moustapha Hassan; Massoud Vosough

Contribution of platelets in tissue regeneration and their possible application in regenerative medicine, which is primarily mediated via secretion of granular components following platelet activation, has been well established in the recent decades. Therefore, platelet rich plasma (PRP), as a portion of plasma with higher concentrations of platelets than the baseline level, is now an attractive therapeutic option in various medical fields mainly for tissue repair and regeneration following injuries. Burn injuries are devastating trauma with high rate of morbidities affecting several aspects of the patient’s life. They require a long-time medical care and high costs. However, even following the best treatment procedures, post-burn scars are inevitable consequence of burn healing process. Therefore, development of new treatment modalities for both burn healing and prevention of post-burn scar establishment seems to be necessary. Regarding the well-known role of PRP in wound healing, here we aimed to provide a comprehensive insight in the possible application of PRP as an adjuvant therapy for the management of burn injuries and subsequent scars. In terms of the following keywords (individually or in combination), original/review articles were searched in PubMed, Scopus, and Google Scholar databases from 2009 to 2021: platelet rich plasma, PRP therapy, platelet biology, platelet function, burn healing, burn scar, scar formation, burn management, wound healing, regenerative medicine. All type of articles or book chapters in English language and relevant data were included in this review. This review initially focused on PRP, its mechanisms of action, preparation methods, and available sources. Then, pathophysiology of burns and subsequent scars were discussed. Finally, their current conventional therapeutic modalities and implication of PRP in their healing process were highlighted.

300-306

Authors: Sara Parsa; Zahra-Soheila Soheili; Hamidreza Alizadeh Otaghvar; Elham Behrangi; Parvin Mansouri; Erik Lubberts; Seyed Javad Mowla

Objective: Psoriasis is a common, auto-immune skin disease characterized by abnormal proliferation and differentiation of keratinocytes. Studies revealed the role of stress stimulators in the pathogenesis of psoriasis. Oxidative stress and heat shock are two important stress factors tuning differentiation and proliferation of keratinocytes, regarding to psoriasis disease. BCL11B is a transcription factor with critical role in embryonic keratinocyte differentiation and proliferation. Given this, in keratinocytes we have investigated potential role of BCL11B in stress-induced differentiation. Furthermore, we searched for a potential intercommunication between BCL11B expression and psoriasis-related keratinocyte stress factors. Materials and Methods: In this experimental study, data sets of psoriatic and healthy skin samples were downloaded in silico and BCL11B was chosen as a potential transcription factor to analyze. Next, a synchronized in vitro model was designed for keratinocyte proliferation and differentiation. Oxidative stress and heat shock treatments were employed on HaCaT keratinocytes in culture, and BCL11B expression level was measured. Cell proliferation rate and differentiation were analyzed by synchronized procedure test. Flow cytometry was done to analyze cell cycle alterations due to the oxidative stress. Results: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) data revealed a significant upregulation of BCL11B expression in keratinocytes, by 24 hours after initiating differentiation. However, it was followed by a significant down-regulation in almost all the experiments, including the synchronized model. Flow cytometer data demonstrated a G1 cell cycle arrest in the treated cells. Conclusion: Results indicated a remarkable role of BCL11B in differentiation and proliferation of HaCaT keratinocytes. This data along with the results of flow cytometer suggested a probable role for BCL11B in stress-induced differentiation, which is similar to what is happening during initiation and progression of normal differentiation.

317-326

Authors: Helia Hamedi; Shakiba Ghorbanian; Leila Mirzaeian; Kataneh Abrari; Paul Mozdziak; Mohammad Taghi Ghorbanian

Objective: Parkinson’s disease (PD) is a neurodegenerative disorder described by the dynamic decline of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Stem cell transplantation is a new therapeutic strategy in the treatment of PD. The objective of the study was to assess the impact of intravenous infusion of adipose-derived mesenchymal stem cells (AD-MSCs) on memory disorder in Parkinsonian rats. Materials and Methods: In this experimental study, male Wistar rats were randomly divided to four groups containing sham, cell treatment, control, and lesion. The cell treatment group received intravenous injection of AD-MSCs 12 days after PD induction by bilateral injection of 6-hydroxydopamine. Four weeks after lesion formation, spatial memory was examined using the Morris water maze (MWM) assessment. The rats’ brains were removed and assessed by bromodeoxyuridine (BrdU), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (Gfap) immunostaining. Results: Statistical analyses revealed a significant addition and reduction in time spent and escape latency in the target quadrant, respectively, in the cell group as compared to the lesion group. Also, BrdU-labeled cells were present in the substantia nigra (SN). The density of TH-positive cells was significantly increased in the AD-MSCs transplantation group as compared to the lesion group, and the density of astrocytes significantly diminished in the AD-MSCs transplantation group as compared to the lesion group. Conclusion: It appears that AD-MSCs treatment for Parkinson’s could decrease the density of astrocytes and promote the density of TH-positive neurons. It appears that AD-MSCs could improve spatial memory impairment in PD.

338-346

Authors: Behnoosh Tayebi; Mohamamd Molazem; Mahnaz Babaahmadi; Erfan Ebrahimi; Mostafa Hajinasrollah; Farhad Mostafaei; Nima Makvand Gholipour; Hossein Baharvand; Mohamadreza Baghaban Eslaminejad; Seyedeh-Nafiseh Hassani; Ensiyeh Hajizadeh-Saffar

Objective: Animal models provide a deeper understanding about various complications and better demonstrate the effect of therapeutic approaches. One of the issues in the low back pain (LBP) model is the invasiveness of the procedure and it does not mimic actual disease conditions in humans. The purpose of the present study was to compare the ultrasound-guided (US-guided) percutaneous approach with the open-surgery method in the tumor necrosis factor-alpha (TNF-α)-induced disc degeneration model for the first time to showcase the advantages of this recently developed, minimally invasive method. Materials and Methods: In this experimental study, eight male rabbits were divided into two groups (open-surgery and US-guided). Relevant discs were punctured by two approaches and TNF-α was injected into them. Magnetic resonance imaging (MRI) was performed to assess the disc height index (DHI) at all stages. Also morphological changes (annulus fibrosus, nucleus pulposus) were evaluated by assessing Pfirrmann grade and histological evaluation (Hematoxylin & Eosin). Results: The findings indicated targeted discs became degenerated after six weeks. DHI in both groups was significantly reduced (P<0.0001), however the difference was not significant between the two groups. In the open-surgery group, osteophyte formation was seen at six and eighteen weeks after the puncture. Pfirrmann grading revealed significant differences between injured and adjacent uninjured discs (P<0.0001). The US-guided method indicated significantly fewer signs of degeneration after six (P=0.0110) and eighteen (P=0.0328) weeks. Histological scoring showed significantly lower degeneration in the US-guided group (P=0.0039). Conclusion: The US-guided method developed a milder grade condition and such a model better mimics the chronic characteristics of LBP and the procedure is more ethically accepted. Therefore, the US-guided method could be a merit approach for future research in this domain as a safe, practical and low-cost method.

354-362

Authors: Seyed Taleb Houseini; Farkhondeh Nemati; Arash Sattari; Mansoureh Azadeh; Roya BishehKolaei

Colorectal cancer (CRC) is the third most prevalent cancer with the second-highest mortality rate worldwide. microRNAs (miRNAs) of cancer-derived exosomes have shown promising diagnosis potential. Recent studies have shown the metastatic potential of a specific group of microRNAs called metastasis. Therefore, down-regulation of miRNAs at the transcriptional level can reduce metastasis probability. The aim of this bioinformatics research is targeting of miRNAs precursors using CRISPR-C2c2 (Cas13a) technique. The C2c2 (Cas13a) enzyme structure was downloaded from the RCSB database, the sequence miRNAs and their precursors were collected from miRbase. The crRNAs were designed and evaluated for their specificity by using CRISPR-RT server. The modeling 3D structure of the designed crRNA was performed by RNAComposer server. Finally, HDOCK server was used to perform molecular docking to evaluate docked molecules' energy level and position. The crRNAs designed for miR-1280, miR-206, miR-195, miR- 371a, miR-34a, miR-27a, miR-224, miR-99b, miR-877, miR-495 and miR-384 that showed high structural similarity with the situation observed in normal and appropriate orientation was obtained. Despite high specificity, the correct orientation was not established in the case of crRNAs that designed to target miR-145, miR-378a, miR-199a, miR- 320a and miR-543. The predicted interactions between crRNAs and Cas13a enzyme showed that crRNAs have a strong potential to inhibit metastasis. Therefore, crRNAs may be considered as an effective anticancer agent for further research in drug development.