@article{ author = {Kandezi, Niyoosha and Mohammadi, Mahsa and Ghaffari, Maryam and Gholami, Mina and Motaghinejad, Majid and Safari, Sepideh}, title = {Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3/Akt/ GSK3 or PI3/Akt/CREB/BDNF Signaling Pathways}, abstract ={Neurodegeneration is a gradual mechanism of neuronal loss arising from numerous cellular and molecular events such as mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis, and the consequence of these processes is neuroplasticity impairment, cognitive diseases, mood-related diseases, and normal cellular activity. Over the last year, major advances have been made in the field of the introduction of herbal compounds with neuroprotective efficacy, one of which is curcumin. Curcumin (diferuloylmethane) is the most abundant turmeric component extracted from the Curcuma longa plant rhizomes. Accumulating evidence indicates that curcumin may induce mitochondrial biogenesis and can function as an antioxidant, anti-inflammatory, and anti-apoptotic agent, which may be used effectively to treat chronic neurodegenerative diseases and any situation in which the neurodegeneration process takes place. Curcumin has been shown to play a critical role in activating two essential signaling pathways phosphatidylinositol-3(PI3)/ protein kinase B(Akt)/ glycogen synthase kinase-3 (GSK3) and PI3/Akt/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and preventing the incidence of neurodegeneration via these two pathways. Curcumin's protective functions against neural cell degeneration due to mitochondrial dysfunction and consequent events such as oxidative stress, inflammation, and apoptosis in neural cells have been documented and clinical data have increased to suggest that curcumin may be a standard candidate as a neuroprotective agent. Therefore, in this review, we summarized the clinical and experimental studies and interpreted the key contributory mechanisms of neuroprotective properties of curcumin in neurodegenerative diseases and disorders. We also tried to understand the function of PI3/Akt/GSK3 and PI3/Akt/CREB/BDNF signaling pathways in the neuroprotective properties of curcumin and tried to evaluate their association with antioxidant, anti-inflammatory, anti-apoptosis and biogenesis effects of mitochondria.}, Keywords = {Curcumin, neuroprotection, PI3/Akt/ GSK3 ,PI3/Akt/CREB/BDNF}, volume = {9}, Number = {1}, pages = {1-32}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.1}, url = {http://ijmcmed.org/article-1-1245-en.html}, eprint = {http://ijmcmed.org/article-1-1245-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} } @article{ author = {Khalilian, Sheyda and Motovali-Bashi, Majid and Rezaei, Halimeh}, title = {Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies for Hemophilia A Patients}, abstract ={A major complication in treating hemophilia A is the development of neutralizing antibodies (inhibitors) against therapeutic administered factor VIII (FVIII), which occurs in approximately 20-30% of patients with severe disease. These inhibitors render FVIII replacement therapy ineffective and increase the morbidity and mortality risk. The currently accepted method to eradicate inhibitors is immune tolerance induction (ITI), and frequent intensive administration of FVIII until inhibitor titers drop. Current ITI protocols are extremely costly and not effective in all patients. During the last decade, many types of research have been accomplished to clarify the mechanisms that mediate immune tolerance induction. Novel experimental therapies including monoclonal antibodies, viral vector-mediated gene therapy, regulatory T cell induction using immunosuppressive drugs, and nanoparticle-based immune modulation show promising results in hemophilia A clinical trials. This review focuses on treatment options towards the anti-FVIII immune responses and current novel therapies in clinical trials.}, Keywords = {Factor VIII, hemophilia A, inhibitors, immune tolerance}, volume = {9}, Number = {1}, pages = {33-49}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.33}, url = {http://ijmcmed.org/article-1-1261-en.html}, eprint = {http://ijmcmed.org/article-1-1261-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} } @article{ author = {Sousa-Lopes, Alejandra and AlvesdeFreitas, Raiany and SilvaCarneiro, Fernando and PedrosaNunes, Kenia and JamesAllahdadi, Kyan and Webb, Robert Clinton and deCassiaTostes, Rita and ReginaGiachini, Fernanda and VitorinoLima, Victor}, title = {Angiotensin (1-7) Inhibits Ang II-mediated ERK1/2 Activation by Stimulating MKP-1 Activation in Vascular Smooth Muscle Cells}, abstract ={The renin–angiotensin system (RAS) exerts profound physiological effects on blood pressure regulation and fluid homeostasis, mainly by modulating renal, cardiovascular, and central nervous systems. Angiotensin (Ang)-(1-7), an end-product of RAS, is recognized by its cardiovascular protective properties through stimulation of the Mas receptor, including vasodilation, anti-inflammatory, and antihypertensive actions, and consequently, counter-regulating the well-known Ang II-elicited actions. The overall hypothesis of this study is that Ang-(1-7) inhibits Ang II-induced ERK1/2 activation in vascular smooth muscle cells (VSMCs), via regulation of mitogen-activated protein phosphatase-1 (MKP-1) activity. Aortas from male Wistar rats were incubated with Ang-(1-7) or vehicle. Concentration-response curves to Ang II were performed in endothelium-denuded aortas, in the presence or absence of ERK1/2 (PD98059) inhibitor or Mas receptor (A-779) antagonist. Expression of proteins was assessed by western blot, and immunohistochemistry was conducted in VSMCs. Ang-(1-7) incubation decreased Ang II-induced contractile response in aortas, and this effect was not observed in the presence of PD98059 or A-779. Stimulation of VSMCs with Ang-(1-7) prevented Ang II-induced ERK1/2 phosphorylation, but not C-Raf-activation. Furthermore, Ang II decreased MKP-1 phosphorylation in VSMCs. Interestingly, simultaneous incubation of Ang-(1-7) with Ang II favored MKP-1 phosphorylation, negatively modulating ERK1/2 activation in VSMCs. The results suggest that Ang-(1-7) counter-regulates actions evoked by Ang II overproduction, as observed in cardiovascular diseases, mainly by modulating MKP-1 activity. This evidence suggests that the role of Ang-(1-7) in MKP-1-regulation represents a target for new therapeutic development.}, Keywords = {Angiotensin (1-7), ERK 1/2, MKP-1, angiotensin-II, renin-angiotensin system, VSMCs, MAPK phosphatase.}, volume = {9}, Number = {1}, pages = {50-61}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.50}, url = {http://ijmcmed.org/article-1-1282-en.html}, eprint = {http://ijmcmed.org/article-1-1282-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} } @article{ author = {Mehri-Ghahfarrokhi, Ameneh and Jami, Mahammad-Saeid and HashemzadehChaleshtori, Mortez}, title = {Upregulation of Neuroprogenitor and Neural Markers via Enforced miR-124 and Growth Factor Treatment}, abstract ={Previous studies have shown that miR-124 plays an important role in the development of auditory neurons, which are degenerated in the sensorineural hearing loss. However, whether the combined use of miR-124 and growth factors can increase the expression of neural related markers in human dental pulp stem cells is unknown so far. In this study, human dental pulp stem cells were transfected with miR-124 following treatment with brain-derived neurotrophic factor or epidermal growth factor/basic fibroblast growth factor. The expression of some neural related markers (nestin, SOX2, β-tubulin III, MAP2, and peripherin) was analyzed in two groups by qRT-PCR or immunofluorescence. Cellular treatment resulted in morphological changes including neurosphere-like colonies formation. Nestin and SOX2 were up-regulated, and MAP2 and peripherin were down-regulated in dental pulp stem cells transfected by miR-124 following treatment with brain-derived neurotrophic factor. Replacement of brain-derived neurotrophic factor with epidermal growth factor/ basic fibroblast growth factor resulted in the up-regulation of nestin, MAP2, peripherin, and β-tubulin III and down-regulation of SOX2. The expression of SOX2 and nestin was also confirmed by immunofluorescence. The combination of miR-124 and growth factors would provide a promising starting point for upregulating the neural progenitor markers in human dental pulp stem cells.}, Keywords = {Spiral ganglion neuron, miR-124, dental pulp stem cells, brain-derived neurotrophic factor, auditory neuropathy.}, volume = {9}, Number = {1}, pages = {62-72}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.62}, url = {http://ijmcmed.org/article-1-1218-en.html}, eprint = {http://ijmcmed.org/article-1-1218-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} } @article{ author = {Fereydouni, Zahra and AmirinezhadFard, Elahe and Mansouri, Kamran and MohammadiMotlagh, Hamid-Reza and Mostafaie, Ali}, title = {Saponins from Tribulus terrestris L. Extract Down-regulate Expression of ICAM-1, VCAM-1 and E-selectin in Human Endothelial Cell Lines}, abstract ={Atherosclerosis is an inflammatory disease in which intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin (SELE) are consistently expressed in the vascular endothelium. Several evidence support the crucial role of adhesion molecules in the development of atherosclerosis and plaque instability. Due to the anti-inflammatory activity of Tribulus terrestris (TT), the present study investigated the effect of aqueous extract and saponin fraction of TT on the expression of ICAM-1, VCAM-1, and SELE genes in endothelial cells during normal and lipopolysaccharide (LPS) induced conditions. Human umbilical vein endothelial cells (HUVEC) and human bone marrow endothelial cells (HBMEC) were cultured, stimulated by LPS, and treated with aqueous extract and saponin fraction of TT. Finally, the expression of ICAM-1, VCAM-1, and SELE genes were measured using quantitative real-time polymerase chain reaction. LPS-induced HUVECs and HBMECs significantly increased the expression of ICAM-1, VCAM-1, and SELE in comparison with control groups (P<0.001). Treatment of LPS-induced HUVECs and HBMECs by aqueous extract and saponin fraction of TT decreased the expression of all three mentioned genes significantly (P<0.001) in comparison with LPS-induced cells. Taken together, our data suggest that TT has an anti-inflammatory effect. In vivo study about anti-inflammatory effect of this herb may provide new insights into the development of a herbal drug for the prevention/therapy of atherosclerosis.}, Keywords = {Atherosclerosis, Tribulus terrestris L., gene expression, adhesion molecules, human endothelial cells, saponin}, volume = {9}, Number = {1}, pages = {73-82}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.73}, url = {http://ijmcmed.org/article-1-1255-en.html}, eprint = {http://ijmcmed.org/article-1-1255-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} } @article{ author = {Moradi, Mohammad-Taher and Hatami, Reza and Rahimi, Zohreh}, title = {Circulating CYTOR as a Potential Biomarker in Breast Cancer}, abstract ={Long non-coding RNAs (lncRNAs) are newly introduced as tumor-related molecules. They are being considered as potential diagnostic and therapeutic targets in cancer studies. Here, we have assessed the importance of CYTOR (linc00152) as a biomarker for the detection of breast cancer in both tumoral tissue and plasma. The relative expression of breast cancer-associated CYTOR was measured in 20 tumoral and paired margin tissues, and moreover, in 80 plasma samples by real-time-polymerase chain reaction. In addition, plasma levels of CA 15-3 were measured using the ELISA test. The receiver operating characteristic curve (ROC) was applied for assessing the sensitivity and specificity of tested biomarkers. The results of the present study disclosed significantly increases in the CYTOR expression levels in tumor tissue with relative quantitation (RQ) equals to 5.15 (P<0.001) and in plasma (RQ =3.03, P<0.01) of breast cancer patients. The area under the ROC curve (AUC) of circulating CYTOR was 0.907 (95% CI: 0.842-0.972, P<0.001), while it was 0.868 (95% CI: 0.783–0.952, P<0.001) for CA 15-3. Based on these findings, we suggest lncRNA CYTOR as a new potential biomarker for breast cancer detection in both solid tumor tissue and plasma.}, Keywords = {Breast cancer, lncRNA, CYTOR, biomarker}, volume = {9}, Number = {1}, pages = {83-89}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.83}, url = {http://ijmcmed.org/article-1-1232-en.html}, eprint = {http://ijmcmed.org/article-1-1232-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} } @article{ author = {Najjari, Abbas and Rahimi, Hamzeh and Nojoumi, Seyed Ali and Omidinia, Eskandar}, title = {Computational Approach for Rational Design of Fusion Uricase with PAS Sequences}, abstract ={Tumor lysis syndrome is a life-threatening condition for humans due to the lack of urate oxidase. In this study, several variants of PASylateduricasefrom the Aspergillus flavus species were analyzed computationally to find the appropriate fusions to solve short half-life and stability concerns. The Ab initio method was performed using Rosetta software to structurally characterize the PAS sequences. The 3D structures of fusions were predicted for fused C- or N-terminally PAS sequences in different lengths to the uricase. The refinement and energy minimization steps revealed that physicochemical and conformational properties of fusions improved while the structures possessed prolonged PAS sequences. Molecular docking results showed that the highest binding affinity to uric acid belonged to uricase-PAS1-100 by the formation of six hydrogens and four non-hydrogen bonds. Altogether, the results indicated that the PASylationprocess would be promising upon the production of urate oxidase with improved solubility and stability.}, Keywords = {Tumor lysis syndrome, Aspergillus flavus, uricase, molecular dynamic, PASylation, plasma half-life}, volume = {9}, Number = {1}, pages = {90-106}, publisher = {Babol University of Medical Sciences}, doi = {10.22088/IJMCM.BUMS.9.1.90}, url = {http://ijmcmed.org/article-1-1291-en.html}, eprint = {http://ijmcmed.org/article-1-1291-en.pdf}, journal = {International Journal of Molecular and Cellular Medicine (IJMCM)}, issn = {2251-9637}, eissn = {2251-9645}, year = {2020} }