Publications by authors named "Kamran Mansouri"

104 Publications

Paper Title "Hu7CG2: A Novel Humanized Anti-Epidermal Growth Factor Receptor (EGFR) Biparatopic Nanobody".

Mol Biotechnol 2021 Mar 26. Epub 2021 Mar 26.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Targeted therapy is an effective and appropriate approach with low side effects in cancer therapy compared with other treatment approaches. Epidermal growth factor receptor, EGFR, is a favorable biomarker as targeted therapy because it overexpresses in several cancers. Monoclonal antibodies are common agents for targeted therapy. Nanobody is the smallest format of monoclonal antibodies with unique properties that include hiding epitope targeting, high stability, low production cost, and ease of connection to other components. The main challenge in targeted therapy by monoclonal antibodies is their immunogenicity due to their non-human nature. In this study, we designed, constructed, and evaluated a novel humanized anti- EGFR biparatopic nanobody, hu7CG2. The hu7CG2 was designed by grafting the complementarity-determining regions of two camelid anti- EGFR nanobodies known as 7C12 and EG2 to a universal scaffold and then connected with a glycine-serine linker. The results of antigen-binding activity and cell viability assays showed that the hu7CG2 inhibited the growth of EGFR overexpression tumor cells. The data showed that hu7CG2 might be a useful tool in the targeting and treatment of tumor cells.
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http://dx.doi.org/10.1007/s12033-021-00317-8DOI Listing
March 2021

The Agglutinin of Common Nettle (Urtica dioica L.) Plant Effects on Gene Expression Related to Apoptosis of Human Acute Myeloid Leukemia Cell Line.

Biochem Genet 2021 Mar 6. Epub 2021 Mar 6.

School of Medicine, Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Treatment of acute myeloid leukemia (AML) requires new drugs as result of a rise in new cases and high disease relapse. Plant lectins with the ability to bind carbohydrates on the cell surface have the potential to treat cancer. Urtica dioica L. agglutinin (UDA) is a low weight lectin with anti-benign prostatic hyperplasia (BPH) impact. Here, we examine the impact of UDA on HL-60 cell line. Cytotoxicity and cytostatic effects were assessed in HL-60 cells treated with UDA and vincristine (positive control). The effects of the lectin on cell cycle phases and cell death mechanism were surveyed by propidium iodide (PI) staining and annexin V/PI, respectively. The activation status of the apoptosis pathway was determined by western blotting. Finally, the expression levels of 84 genes were examined by the Human cancer drug target gene PCR array kit. The results indicated that the increase in UDA concentration inhibited the proliferation of HL-60 cells as well as apoptosis induction. Cell cycle analysis showed that the number of sub G1 cells increased essentially. Experimental observations showed that UDA can induce cell apoptosis through a caspase 9-dependent pathway. The expression changes of 21 genes confirmed the apoptotic events in HL-60 cells treated with UDA. In this, we have presented the first investigation on the cytotoxic and apoptotic effects of a lectin isolated from rhizomes and roots of Urtica dioica L. on human AML cells. Generally, the results suggest that UDA may have therapeutic value for leukemia and would be studied further as a new drug for AML later on.
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http://dx.doi.org/10.1007/s10528-020-10024-9DOI Listing
March 2021

Generating the Engineered Form of a Nanobody Against Placenta Growth Factor with High Antiangiogenesis Potential.

Monoclon Antib Immunodiagn Immunother 2021 Feb;40(1):11-16

Department of Medical Biotechnology and Molecular Science, North Khorasan University of Medical Science, Bojnurd, Iran.

Antibody engineering is a dynamic field in antibody industry. Over 30% of novel monoclonal antibodies (mAbs) in R&D and clinical trials are engineered forms. Affinity enhancement contributes to the development of new binders that are not only effective in low dose and cost but also improve some drawbacks of antibody production. After previous successful work on affinity maturation of nanobody against placenta growth factor and finding the best engineered nanobodies (Mut2:S31D and Mut4:R45E), according to bioinformatic parameters and molecular dynamics (MD) simulation results, in this study we focused on experimental confirmation of affinity enhancement of a mutant form of nanobody. So, we cloned and expressed two of four mutant forms in pHEN6c vector. Affinity binding was assayed by enzyme-linked immunosorbent assay on purified mutants, with results showing that 10-time enhancement in affinity compared with the native form associated with MD simulation results. We checked the effectiveness of these mutant nanobodies in angiogenesis inhibition by human umbilical vein endothelial cell proliferation and 3D capillary tube formation. EC50 of mut2, mut4, and native in proliferation assay was 110, 140, and 190 ng/mL, respectively, and that in 3D capillary tube formation was 80, 83, and 100 ng/mL. The results of functional studies revealed strong effectiveness of Mut2 followed by Mut4 compared with the native form. Our study confirmed that approach could facilitate development of novel versions of mAb with better characteristics, which could save cost and time.
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http://dx.doi.org/10.1089/mab.2020.0023DOI Listing
February 2021

The effect of polymorphisms (174G> C and 572C> G) on the Interleukin-6 gene in coronary artery disease: a systematic review and meta-analysis.

Genes Environ 2021 Jan 12;43(1). Epub 2021 Jan 12.

Department of Nursing, School of Nursing and Midwifery, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Coronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease.

Methods: This study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I index in the Comprehensive Meta-Analysis software.

Results: The GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85.

Conclusion: This study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.
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http://dx.doi.org/10.1186/s41021-021-00172-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802194PMC
January 2021

Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm.

J Inflamm (Lond) 2020 Oct 29;17(1):33. Epub 2020 Oct 29.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient's death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.
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http://dx.doi.org/10.1186/s12950-020-00263-3DOI Listing
October 2020

Perfluorocarbon as an adjuvant for tumor anti-angiogenic therapy: Relevance to hypoxia and HIF-1.

Med Hypotheses 2021 Jan 10;146:110357. Epub 2020 Nov 10.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Lack of vascularization results in increased demand for oxygen and creates a defined feature of the tumor microenvironment known as tumor hypoxia. It is well established that in response to hypoxia, hypoxia-inducible factor-1 α (HIF-1α) is induced which is an important factor in angiogenesis, invasion and metastasis. In turn, HIF-1α regulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF). Ascribed to abnormal characteristics of tumor angiogenic networks, antiangiogenic therapy approaches can even worsen the hypoxic condition and can create cancer cells with stemness features. Hence oxygen delivery via perfluorocarbon (PFC) to hypoxic sites seems to result in unstable HIF expression and consequent inactivation of angiogenesis cascade and metastasis and therefore, inhibition of cancer cells stemness.
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http://dx.doi.org/10.1016/j.mehy.2020.110357DOI Listing
January 2021

Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm.

J Inflamm (Lond) 2020 29;17:33. Epub 2020 Oct 29.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient's death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.
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http://dx.doi.org/10.1186/s12950-020-00263-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594974PMC
October 2020

Association between serum paraoxonase 1 activity and its polymorphisms with multiple sclerosis: a systematic review.

Neurol Sci 2021 Feb 23;42(2):491-500. Epub 2020 Oct 23.

Medical Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Human serum paraoxonase (PON) is an enzyme that is synthesized by the liver and enters the bloodstream, and it is transmitted by high-density lipoproteins (HDL). Paraoxonase 1 (PON1) is a hydrolytic enzyme with a wide range of substrates and the ability to protect against lipid oxidation. In this study, due to the activity of PON1 in the brain and its antioxidant effects on the reduction of neurological disorders in the central nervous system, the role of PON1 and its polymorphisms related to multiple sclerosis has been examined to enhance treatment methods.

Methods: This article is a systematic review. In this study, the role of PON1 and its polymorphisms in multiple sclerosis (MS) has been investigated. Articles published in Persian and international databases of SID, Google Scholar, ISI (WoS), Magiran, PubMed, Scopus, IranDoc, Science Direct, and Iran Medix were examined, using the search keywords of Paraoxonase 1, polymorphism, multiple sclerosis, and PON1.

Results: PON1 is undoubtedly a potential factor in the pathogenesis of multiple sclerosis, and it plays an important role in protecting antioxidants in the blood. Oxidative stress and lipid peroxidation are factors in the pathogenesis of MS. Both inflammatory cytokines and oxidative stress have a detrimental effect on PON1. However, reducing the activity of PON1 may help to restore the pathogenesis of the disease.

Conclusion: Decreased PON1 activity and PON1 polymorphism are associated with several neurological diseases, including ischemic stroke, white matter lesions (WMLs), amyotrophic lateral sclerosis (ALS), dementia, and Parkinson's disease. PON1-55M alleles in Italians and PON1-192Q alleles in Poles were associated with a high risk of MS. Moreover, PON1-55 and PON1-192 polymorphisms were not associated with MS onset age, nor its evolutionary type.
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http://dx.doi.org/10.1007/s10072-020-04842-3DOI Listing
February 2021

Regenerative Medicine and Angiogenesis; Challenges and Opportunities.

Adv Pharm Bull 2020 Sep 9;10(4):490-501. Epub 2020 Aug 9.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Blood vessel development is one of the most prominent steps in regenerative medicine due to the restoration of blood flow to the ischemic tissues and providing the rapid vascularization in clinical-sized tissue-engineered grafts. However, currently tissue engineering technique is restricted because of the inadequate tissue vascularization. Some challenges like as transportation in large scale, distribution of the nutrients and poor oxygen diffusion limit the progression of vessels in smaller than clinically relevant dimensions as well integration. In this regard, the scholars attempted to promote the vascularization process relied on the stem cells (SCs), growth factors as well as exosomes and interactions of biomaterials with all of them to enable the emergence of ideal microenvironment which is needed for treatment of unhealthy organs or tissue regeneration and formation of new blood vessels. Thus, in the present review we aim to describe these approaches, advances, obstacles and opportunities as well as their application in regeneration of heart as a prominent angiogenesis-dependent organ.
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http://dx.doi.org/10.34172/apb.2020.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539317PMC
September 2020

Indicated and non-indicated antibiotic administration during pregnancy and its effect on pregnancy outcomes: Role of inflammation.

Int Immunopharmacol 2020 Dec 14;89(Pt B):107081. Epub 2020 Oct 14.

Maternal, Fetal and Neonatal Research Center, Tehran University of Medical Sciences, Tehran, Iran; Breastfeeding Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The objective of this study was to compare the release of endotoxin and pro-inflammatory cytokines as well as pregnancy outcomes after antibiotic exposure in healthy and bacterial infected pregnant rats. Thirty female Wistar pregnant rats were divided into five groups. Group A considered as control and received intraperitoneal saline 0.9% on 17th day of gestation or DG) and groups B and C treated with 20 mg/kg/day intravenous ceftriaxone and ceftazidime, respectively (DG: 18-20). Groups D and E received intraperitoneal E. coli and LPS on 17th DG respectively. Also, groups F and G received the same treatment as group D but they treated with the exact antibiotics mentioned for groups B and C (same dose and duration). Pregnancy outcomes as well as maternal sera levels of endotoxin, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 were assessed using enzyme-linked immunosorbent assay. It was shown that group B had a higher IL-1β (P = 0.003) and TNF-α (P = 0.003) levels compared to the controls (CTC). Group C expressed a lower gestational duration (P = 0.007) as well as higher IL-6 (P = 0.025) and TNF-α (P < 0.001) levels CTC. Interestingly, both group B (P = 0.021) and C (P < 0.001) had a higher rate of endotoxin release CTC. Moreover, in group C, IL-6 (P < 0.0001 and r = -0.941) had a significant correlation with gestational duration. As the results showed, antibiotic administration in non-indication condition seems to be associated with significantly higher production of endotoxin and inflammatory cytokines which increase the risk of poor pregnancy outcomes.
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http://dx.doi.org/10.1016/j.intimp.2020.107081DOI Listing
December 2020

Urtica dioica agglutinin (a plant lectin) has a caspase-dependent apoptosis induction effect on the acute lymphoblastic leukemia cell line.

Cell Mol Biol (Noisy-le-grand) 2020 Sep 30;66(6):121-126. Epub 2020 Sep 30.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Urtica dioica agglutinin (UDA) is a very small plant lectin with anti-prostatic activity. In this study, we investigated the effect of UDA on proliferation and apoptosis induction in human acute lymphoid leukemia (ALL) cell lines. The effect of UDA on Jurkat and Raji cell proliferation was examined by MTS assay. Distribution of cell cycle phases was determined by PI staining and apoptosis was examined with annexin V/PI and western blot. Results showed UDA treatment reduced cell proliferation in cells by inducing apoptosis. PI staining was associated with a higher percentage of the cell population in sub G1. Caspase-8 and caspase-9 dependent apoptosis occurred in Jurkat cells. Generally, UDA treatment resulted in cell death in ALL cell lines and induced apoptosis in the T-ALL cell line, Jurkat, through extrinsic and intrinsic pathways. These results may be considered as a guide to working on UDA as an anti-leukemic drug in the future.
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September 2020

The emerging role of targeting cancer metabolism for cancer therapy.

Tumour Biol 2020 Oct;42(10):1010428320965284

Medical Biology Research Center, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells' bioenergetics differently. Tumor cells' dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.
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http://dx.doi.org/10.1177/1010428320965284DOI Listing
October 2020

Development of a Recombinant Monospecific Anti-PLGF Bivalent Nanobody and Evaluation of it in Angiogenesis Modulation.

Mol Biotechnol 2020 Dec 25;62(11-12):580-588. Epub 2020 Sep 25.

Department of Medical Biotechnology and Molecular Science, North Khorasan University of Medical Science, Bojnurd, Iran.

During the past two decades, tumor therapy based on monoclonal antibody has been found as a confident therapeutic approach in solid tumors and hematologic malignancies. Nanobodies are the smallest fragment of an antigen-binding domain in heavy chain-only antibody originated from the Camelidae family. Accordingly, they are being recently developed rapidly as diagnostic and therapeutic agents. In this regard, targeting of angiogenic factors like Placenta growth factor (PLGF) via nanobodies show a high effectiveness. In the current study, we developed a recombinant anti-PLGF bivalent nanobody based on the affinity enhancement mutant form of anti-PLGF nanobody to suppress the angiogenesis progression. Thereafter, the bivalent nanobody (bi-Nb) was cloned and then expressed into a bacterial system. Afterward, the purity was authorized using western blot assay and the affinity was assessed using ELISA. In this regard, proliferation, 3D capillary tube formation, and migration assays were employed as functional assays. The obtained data were analyzed using t-test and P < 0.05 was considered as statistically significant. The results indicate that the bivalent nanobody could inhibit proliferation, mobility, and formation of endothelial cell capillary-like structure. Moreover, the EC50 was estimated for endothelial cell's proliferation and capillary tube's formation to be about 100 ng/ml and 65 ng/ml, respectively. Migration of MCF-7 was inhibited as about 69%, rather than the control. Accumulation of data have shown that targeting of angiogenic factors like VEGF via monoclonal antibodies or nanobodies can be useful in the suppression of tumor progression. Also, the inhibition of PLGF with monoclonal antibody indicated that it is significant in angiogenesis suppression. However, due to intrinsic properties of nanobodies, they are suggested to be used. Since the small size is rapidly removed through liver or kidney system, so it is important to use bivalent or polymeric forms for extending the half-life. Our findings indicated that the inhibition of PLGF can prevent growth and proliferation of endothelial cells and tumor cells through the bivalent nanobody. So, it is suggested as a novel therapeutic agent for angiogenesis suppression.
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http://dx.doi.org/10.1007/s12033-020-00275-7DOI Listing
December 2020

Production of monoclonal antibody against recombinant bovine sex-determining region Y (SRY) and their preferential binding to Y chromosome-bearing sperm.

Reprod Domest Anim 2021 Feb 3;56(2):270-277. Epub 2021 Jan 3.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Separation of X and Y chromosome-bearing sperm is an appropriate method for the selection of desired sex of offspring to increase the profit in livestock industries. The purpose of this study was the production of a monoclonal antibody against recombinant bovine sex-determining region Y protein for separation Y sperm. The hybridoma cells from splenocytes of immunized female's balb/C mice and Sp2/0 cells were made. The binding affinity of our monoclonal antibody (mAbSRY2) was compared with mouse monoclonal SRY-15. The Western blot method indicated that mAbSRY2 successfully detected the rbSRY protein. The specificity and sensitivity of mAbSRY2 is comparable to SRY-15 commercially ones. The SRY gene in 100% of bull semen contains the Y chromosome that had the strongest binding affinity to mAbSRY2 was synthesized. In other words, the binding affinity of semen contains the X sperms near the negative control. In general, this immunological method can help to separate X from Y sperms. However, the mAbSRY2 is bind to Y-bearing sexed sperm, but in the future; the sexed sperms need to apply in farms.
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http://dx.doi.org/10.1111/rda.13821DOI Listing
February 2021

Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational.

Biomed Pharmacother 2020 Nov 27;131:110694. Epub 2020 Aug 27.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

As a process entailing a high turnover of the host cell molecules, viral replication is required for a successful viral infection and requests virus capacity to acquire the macromolecules required for its propagation. To this end, viruses have adopted several strategies to harness cellular metabolism in accordance with their specific demands. Most viruses upregulate specific cellular anabolic pathways and are largely dependent on such alterations. RNA viruses, for example, upregulate both glycolysisand glycogenolysis providing TCA cycle intermediates essential for anabolic lipogenesis. Also, these infections usually induce the PPP, leading to increased nucleotide levels supporting viral replication. SARS-CoV-2 (the cause of COVID-19)that has so far spread from China throughout the world is also an RNA virus. Owing to the more metabolic plasticity of uninfected cells, a promising approach for specific antiviral therapy, which has drawn a lot of attention in the recent years, would be the targeting of metabolic changes induced by viruses. In the current review, we first summarize some of virus-induced metabolic adaptations and then based on these information as well as SARS-CoV-2 pathogenesis, propose a potential therapeutic modality for this calamitous world-spreading virus with the hope of employing this strategy for near-future clinical application.
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http://dx.doi.org/10.1016/j.biopha.2020.110694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451059PMC
November 2020

Human plasma protein corona decreases the toxicity of pillar-layer metal organic framework.

Sci Rep 2020 09 3;10(1):14569. Epub 2020 Sep 3.

Department of Chemistry, Faculty of Chemical Science, Firoozabad Branch, Islamic Azad University, P.O. Box 74715-117, Firoozabad, Fars, Iran.

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L)].1.3DMA (MOF-1) {L = 4, 4-bipyridine and L = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.
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http://dx.doi.org/10.1038/s41598-020-71170-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471913PMC
September 2020

Clinical effects of curcumin in enhancing cancer therapy: A systematic review.

BMC Cancer 2020 Aug 24;20(1):791. Epub 2020 Aug 24.

Department of Biology, Islamic Azad University Urmia, Urmia, Iran.

Background: Curcumin is herbal compound that has been shown to have anti-cancer effects in pre-clinical and clinical studies. The anti-cancer effects of curcumin include inhibiting the carcinogenesis, inhibiting angiogenesis, and inhibiting tumour growth. This study aims to determine the Clinical effects of curcumin in different types of cancers using systematic review approach.

Methods: A systematic review methodology is adopted for undertaking detailed analysis of the effects of curcumin in cancer therapy. The results presented in this paper is an outcome of extracting the findings of the studies selected from the articles published in international databases including SID, MagIran, IranMedex, IranDoc, Google Scholar, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant publications were selected based on the plausible keywords, in accordance with the study aims, as follows: prevalence, curcumin, clinical features, cancer.

Results: The results are derived based on several clinical studies on curcumin consumption with chemotherapy drugs, highlighting that curcumin increases the effectiveness of chemotherapy and radiotherapy which results in improving patient's survival time, and increasing the expression of anti-metastatic proteins along with reducing their side effects.

Conclusion: The comprehensive systematic review presented in this paper confirms that curcumin reduces the side effects of chemotherapy or radiotherapy, resulting in improving patients' quality of life. A number of studies reported that, curcumin has increased patient survival time and decreased tumor markers' level.
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http://dx.doi.org/10.1186/s12885-020-07256-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446227PMC
August 2020

Saponins from Tribulus terrestris L. Extract Down-regulate the Expression of ICAM-1, VCAM-1 and E-selectin in Human Endothelial Cell Lines.

Int J Mol Cell Med 2020 ;9(1):73-83

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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 (TT), the present study investigated the effect of aqueous extract and saponin fraction of TT on the expression of , , and 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 , and genes were measured using quantitative real-time polymerase chain reaction. LPS-induced HUVECs and HBMECs significantly increased the expression of , , and 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. 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.
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http://dx.doi.org/10.22088/IJMCM.BUMS.9.1.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422852PMC
January 2020

Effects of sodium alginate capsules as 3D scaffolds on hormones and genes expression in preantral follicles of mice compared to 2D medium: An experimental study.

Int J Reprod Biomed 2020 Jul 22;18(7):517-530. Epub 2020 Jul 22.

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: The improvement of in vitro maturation methods, which can activate the preantral follicle growth, plays a crucial role in the production of mature oocytes in reproductive technology.

Objective: To evaluate the different concentrations of 3D scaffolds of sodium alginate on hormones and gene expression in mice preantral follicles.

Materials And Methods: Immature female BALB/c mice (12-14 days) were sacrificed. The follicles were removed mechanically and transferred into α minimal essential medium with 5% fetal bovine serum. The preantral follicles were incubated with different concentrations of sodium alginate (0.25%, 0.5%, and 1%) and 2D medium for 12 days. The follicles were examined for antral formation following the 10th day and the diameter on days 6 and 12 . The levels of hormones (AMH, androstenedione, 17 -estradiol, and progesterone) and the expression of genes (, , , , and ) at the end of the 12 day.

Results: Maximum follicle diameter and highest percentage of antrum formation were related to 0.5% concentration (p = 0.00). The levels of hormones in different doses of sodium alginate were increased significantly compared to the control group (p = 0.00). The highest and lowest levels of these hormones were related to 0.5% concentration and 2D medium, respectively. The highest level of genes expression was observed in 0.5% sodium alginate, which showed a significant increase compared to the control group (p = 0.00).

Conclusion: Proper concentration of alginate hydrogel increases follicle growth, causes follicle maturation, produces steroid hormones, and increases appropriate expression of steroidogenesis-related genes.
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http://dx.doi.org/10.18502/ijrm.v13i7.7369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385913PMC
July 2020

MiR-646 prevents proliferation and progression of human breast cancer cell lines by suppressing HDAC2 expression.

Mol Cell Probes 2020 10 8;53:101649. Epub 2020 Aug 8.

Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. Electronic address:

Background: Breast cancer is a type of cancer with a high incidence and mortality rate worldwide. Change in epigenetic mechanisms enhances cancer cell progression. Histon deacetylase 2 (HDAC2) was found to act as a potential oncogene in different malignancies. For better understanding the mechanisms related to breast cancer development, we investigated the role of HDAC2 in breast cancer and the inhibitory effect of miR-646 on this oncogene.

Methods: A total of thirty cancerous tissues and 30 adjacent non-cancerous specimens and also three breast cancer cell lines were enrolled in the study. Quantitative reverse transcriptase PCR (qRT-PCR) was employed to detect the HDAC2 and miR-646 expression level in the studied samples. The biological roles of HDAC2 and miR-646 were investigated through manipulating the expression level of HDAC2 or miR-646 in breast cancer cells. Finally, we evaluated whether the HDAC2 is a direct target for miR-646.

Results: In this study, we found HDAC2 is significantly upregulated in cancerous specimens and cell lines compared to non-cancerous tissues and normal cell line. On the other hand, miR-646 expression was decreased in clinical specimens and breast cancer cells compared to non-cancerous samples. Knocking out of the HDAC2 and overexpression of miR-646 inhibited breast cancer cell growth but promoted cell death, while untreated groups showed inverse results. Furthermore, we showed that in the breast cancer cells, miR-646 regulates the progression and proliferation by suppressing HDAC2.

Conclusion: Taken together, our study identified a miR-646/HDAC2 regulatory function in the breast cancer development and introduced a therapeutically target for breast cancer.
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http://dx.doi.org/10.1016/j.mcp.2020.101649DOI Listing
October 2020

Heterologous expression, purification, and refolding of SRY protein: role of L-arginine as analyzed by simulation and practical study.

Mol Biol Rep 2020 Aug 22;47(8):5943-5951. Epub 2020 Jul 22.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Escherichia coli is a widely-used cell factory for recombinant protein production, nevertheless, high amount of produced protein is seen in aggregated form. The purpose of this study was to improve the solubility of recombinant bovine sex-determining region Y protein (rbSRY) by exploring the effect of temperature, inducer, and water-arginine mixed solvent. Codon-optimized rbSRY expressed in Rosetta-gami B (DE3) pLysS and purified by NI-NTA His-select affinity chromatography in the native and denaturing conditions. A three-dimensional model of SRY was built and studied through molecular dynamics simulations in water and in the presence of L-arginine as co-solvent. Results indicated the significant effects of temperature and IPTG concentration (P < 0.001) on the solubility of rbSRY. The binding activity of native, inclusion bodies and refolded fractions to anti-rbSRY monoclonal antibody were concentration-dependent (P < 0.001). Based on molecular modeling results, the propensity of fragments in the N-terminal domain to form β-sheet and the relative instability of α-helices in terminal domains are the probable reasons for the high aggregation potential of SRY, which are mitigated in the presence of L-arginine. Altogether, our rbSRY protein was properly produced and applying appropriate culture conditions could help enhance its solubility, refold inclusion bodies, and improve its activity upon refolding.
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http://dx.doi.org/10.1007/s11033-020-05667-1DOI Listing
August 2020

Medicinal Plants Extracts with Antiangiogenic Activity: Where Is the Link?

Adv Pharm Bull 2020 Jul 11;10(3):370-378. Epub 2020 May 11.

Medical Biology Research Center Medical Sciences, Health Technology Institute, Kermanshah, Iran.

Angiogenesis is a strictly controlled process defined as the formation of new blood vessels essential for certain physiologic and pathologic conditions where the latter includes tumor growth, development, and metastasis. Thus, inhibiting angiogenesis along with other anticancer strategies such as chemotherapy seems to be invaluable for reaching an optimal outcome in cancer patients. It has been shown that some natural plant-derived compounds are capable of preventing the formation of these new blood vessels in the tumor and also inhibit the proliferation and growth of the cancer cells. In this review, we intend to introduce plants with anti-angiogenic properties and discuss their related features.
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http://dx.doi.org/10.34172/apb.2020.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335987PMC
July 2020

Rapamycin Reduces Cervical Cancer Cells Viability in Hypoxic Condition: Investigation of the Role of Autophagy and Apoptosis.

Onco Targets Ther 2020 18;13:4239-4247. Epub 2020 May 18.

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Rapamycin has been known as an anti-cancer agent that affects different malignancies such as glioblastoma and prostate cancer. However, there are few studies concerning rapamycin effects on the cervical cancer cells. In this study, it was aimed to investigate the possible effect of rapamycin on a cervical cancer cell line and explored the possible mechanism(s) and pathway(s) for this agent.

Materials And Methods: To do so, HeLa cells as cervical cancer cell line were used and treated with different concentrations of rapamycin under both normoxic and hypoxic conditions. Then, cell viability assays, Western blot, quantitative real-time polymerase chain reaction (QR-PCR), acridine orange and acridine orange/propidium iodide staining were performed to evaluate rapamycin effect on the mentioned cell line.

Results: The results showed that autophagy and apoptosis-related genes increased significantly in rapamycin-treated HeLa cells compared to controls. Moreover, cervical cancer cell death by rapamycin-induced autophagy in hypoxia was greater than normoxia compared with controls. In this study, it was showed that autophagy induction by rapamycin can mediate programmed cell death of cervical cancer cells, especially in hypoxic condition.

Conclusion: These findings provide a new evidence that rapamycin may inhibit hypoxic HeLa cell proliferation through the trigger of programmed cell death, facilitating the development of novel anti-cancer therapy.
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http://dx.doi.org/10.2147/OTT.S249985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244242PMC
May 2020

Anti-angiogenic effects of testis-specific gene antigen 10 on primary endothelial cells.

Gene 2020 Sep 5;754:144856. Epub 2020 Jun 5.

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Growing evidence indicates the antitumor and antiangiogenesis activities of testis-specific gene antigen 10 (TSGA10). However, the underlying mechanisms and precise role of TSGA10 in angiogenesis are still elusive. In this study, we isolated human umbilical cord vein endothelial cells (HUVECs) and stably transfected with pcDNA3.1 carrying TSGA10 coding sequence. We demonstrated that TSGA10 over-expression significantly decreases HUVEC tubulogenesis and interconnected capillary network formation. HUVECs over-expressing TSGA10 exhibited a significant decrease in migration and proliferation rates. TSGA10 over-expression markedly decreased expression of angiogenesis-related genes, including VEGF-A, VEGFR-2, Ang-1, Ang-2, and Tie-2. Our ELISA results showed the decrease in VEGF-A mRNA expression level is associated with a significant decrease in its protein secretion. Additionally, over-expressing TSGA10 decreased expression levels of marker genes of cell migration (MMP-2, MMP-9, and SDF-1a) and proliferation (PCNA and Ki-67. Furthermore, ERK-1 and AKT phosphorylation significantly reduced in HUVECs over-expressing TSGA10. Our findings suggest a potent anti-angiogenesis activity of TSGA10 in HUVECs through down-regulation of ERK and AKT signalling pathways, and may provide therapeutic benefits for the management of different pathological angiogenesis.
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http://dx.doi.org/10.1016/j.gene.2020.144856DOI Listing
September 2020

Effect of Tribulus Terrestris L. on Expression of ICAM-1, VCAM-1, E-Selectin and Proteome Profile of Human Endothelial Cells In-Vitro.

Iran J Immunol 2020 Mar;17(1):64-74

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol.

Objective: To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L. (TT) on the proteome and expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the human umbilical vein endothelial cell (HUVEC) and human bone marrow endothelial cell (HBMEC) lines.

Methods: Two cell lines were cultured and induced with lipopolysaccharide (LPS). The primed cells were then treated with aqueous extract and saponin fraction of TT. The protein profile of the endothelial cells was assessed under normal and LPS-induced conditions using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 2D gel electrophoresis (2-DE). The levels of VCAM-1, ICAM-1, and E-selectin were estimated by use of western blotting.

Results: LPS-induced HUVECs and HBMECs were shown to significantly increase the expression of ICAM-1, VCAM-1, and E-selectin in comparison to control groups. Our findings revealed that TT extract resulted in significantly more reduced levels of proteome (80 spots) as well as all the three mentioned proteins compared with the effect of saponin fraction alone.

Conclusion: TT extract and its saponin fraction exerted anti-inflammatory effects on HUVEC and HBMEC lines and reduced the expression of ICAM-1, VCAM-1, and E-selectin. However, the anti-inflammatory effect of aqueous extract was greater than that of saponin fraction. Therefore, TT could be considered as a potential candidate for the treatment or prevention of atherosclerosis.
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http://dx.doi.org/10.22034/iji.2020.80295DOI Listing
March 2020

TSGA10 Over Expression Decreases Metastasic and Metabolic Activity by Inhibiting HIF-1 in Breast Cancer Cells.

Arch Med Res 2020 01 18;51(1):41-53. Epub 2020 Feb 18.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical sciences, Kermanshah, Iran; Department of Molecular Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background And Aims: HIF-1 is an important factor that play critical roles in metabolic and metastasis activity of cancer cells. HIF-1 activity can have regulated by TSGA10. Although decreased metastatic activity of cancer cells through TSGA10 inhibitory effect on HIF-1 have already been demonstrated, changes in cancer metabolism and its impact on metastasis in breast cancer is still not determined. So, we aimed to investigate TSGA10 overexpression effect on breast cancer metabolism as well as metastasis.

Methods: TSGA10 vector was designed and stable transfected into MCF-7 cells. The efficiency of transfection was assessed by Real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67 and E-cadherin in cancer cells were measured.

Results: Our results showed decrease of cell proliferation and cell cycle arrest in G2/M phase. Reduce expression of GLUT1, lactate production and reactive oxygen species (ROS) below their basal level indicated decreased metabolic activity. Furthermore, metastatic activity reduction was shown by decrease expression of different involve genes in metastasis, protelytic activity of MMOLP-2/9, carbonic anhydrase (CA) IX activity and increase of wound closure. Moreover, except for E-cadherin, expression of ER, PR, HER2 and Ki67 was declined in cells.

Conclusion: Our findings indicated that TSGA10 overexpression could decrease the metastatic and metabolic activity of cancer cells through its inhibitory effect on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.
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http://dx.doi.org/10.1016/j.arcmed.2019.12.002DOI Listing
January 2020

Characterization and anti-diabetic effects of the oligosaccharide fraction isolated from Rosa canina in STZ-Induced diabetic rats.

Carbohydr Res 2020 Mar 24;489:107927. Epub 2020 Jan 24.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Diabetes mellitus is the most common metabolic disorder characterized by chronic hyperglycemia. There has been a surge of research studies aiming to use natural products in the management of diabetes. The objective of this study was to isolate and characterize the structure and anti-diabetic mechanisms of the main ingredient from Rosa canina. The oligosaccharide was isolated from Rosa canina fruits and characterized by a combination of FTIR, NMR and Mass spectrometry. Wistar rats were divided into negative control, diabetic (type 2), isolated oligosaccharide (IO)-treated diabetic and positive diabetic controls. Oral glucose tolerance, gluconeogenesis and α-glucosidase inhibitory tests as well as immunohistochemistry and quantitative real time-PCR were performed to elucidate the molecular anti-diabetic mechanisms of IO. Structural analyses confirmed the oligosaccharide structure of isolated fraction. Gluconeogenesis and α-glucosidase activity were inhibited by IO in diabetic rats. The oral glucose tolerance test was improved significantly in the group treated with the IO (P < 0.05). Pancreatic β-cells and tissue pathological examination showed a significant improvement after the treatment period. In addition, the expression of Ngn3, Nkx6.1 and insulin increased in oligosaccharide-treated compared to untreated diabetic rats. Owing to the verified anti-diabetic effects and regenerative potential, isolated oligosaccharide could be considered as the promising drug in the management of diabetes.
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http://dx.doi.org/10.1016/j.carres.2020.107927DOI Listing
March 2020

Autophagy related gene expression status in patients diagnosed with azoospermia: A cross-sectional study.

J Gene Med 2020 04 7;22(4):e3161. Epub 2020 Feb 7.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Autophagy affects various aspects of the male reproductive system. Any defects in this process may lead to azoospermia. However, the exact molecular mechanisms of the autophagy pathway have remained largely obscure. Therefore, the present study aimed to investigate levels of autophagy pathway gene expression (i.e. Lc3B, Beclin1, ATG5 and Bcl2) in azoospermic patients.

Methods: The levels of Lc3B, Beclin1, ATG5 and Bcl2 mRNA expression in azoospermic patients and fertile males were evaluated by a real-time polymerase chain reaction technique. In addition, diagnostic evaluation based on the receiver-operating characteristic (ROC) curve was performed.

Results: The results obtained showed the decreased expression of Lc3B, Beclin1 and ATG5 genes in infertile patients compared to the control group (p < 0.05), whereas Bcl2 expression was increased in samples (p < 0.05). A diagnostic evaluation by ROC curve and calculation of the area under the curve showed that, using a cut-off relative quantification of 4.550, 0.052, 0.056 and 0.012, the sensitivity of Lc3B, Beclin1, ATG5 and Bcl2 genes was 87.5%, 93.8%, 93.8% and 90%, respectively. In addition, a specificity of 76.7%, 76.7%, 93.3% and 81.2%, respectively, was observed.

Conclusions: As a first study, the current research suggests that an alteration in the expression of autophagy pathway genes may be associated with male infertility. Based on our finding, the increased expression of Bcl2 and formation of Becline1/Bcl2 complex, which inhibits Beclin1 recruitment, may lead to a decrease of the autophagy process in azoospermic patients. Accordingly, upon further investigation, the autophagy could be considered as an important aspect during spermatogenesis.
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http://dx.doi.org/10.1002/jgm.3161DOI Listing
April 2020

Cannabinoids: a possible treatment for chronic cutaneous wounds.

J Dermatolog Treat 2021 Feb 20;32(1):128-129. Epub 2019 Nov 20.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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http://dx.doi.org/10.1080/09546634.2019.1690620DOI Listing
February 2021