Seyed Nooreddin Faraji | Shiraz University Of Medical Sciences (original) (raw)

Papers by Seyed Nooreddin Faraji

PubMed, Apr 30, 2024

Aim: Streptokinase has poor selectivity and provokes the immune response. In this study, we used ... more Aim: Streptokinase has poor selectivity and provokes the immune response. In this study, we used in silico studies to design a fusion protein to achieve targeted delivery to the thrombus. Materials & methods: Streptokinase was analyzed computationally for mapping. The fusion protein modeling and quality assessment were carried out on several servers. The enzymatic activity and the stability of the fusion protein and its complex with plasminogen were assessed through molecular docking analysis and molecular dynamics simulation respectively. Results: Physicochemical properties analysis, protein quality assessments, protein-protein docking and molecular dynamics simulations predicted that the designed fusion protein is functionally active. Conclusion: Our results showed that this fusion protein might be a prospective candidate as a novel thrombolytic agent with better selectivity.

PubMed, Dec 30, 2023

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully tar... more Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies. Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated. Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner. Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

BMC cancer, Jan 31, 2024

Background Breast cancer remains a significant health challenge worldwide, necessitating the iden... more Background Breast cancer remains a significant health challenge worldwide, necessitating the identification of reliable biomarkers for early detection, accurate prognosis, and targeted therapy. Materials and methods Breast cancer RNA expression data from the TCGA database were analyzed to identify differentially expressed genes (DEGs). The top 500 up-regulated DEGs were selected for further investigation using random forest analysis to identify important genes. These genes were evaluated based on their potential as diagnostic biomarkers, their overexpression in breast cancer tissues, and their low median expression in normal female tissues. Various validation methods, including online tools and quantitative Real-Time PCR (qRT-PCR), were used to confirm the potential of the identified genes as breast cancer biomarkers. Results The study identified four overexpressed genes (CACNG4, PKMYT1, EPYC, and CHRNA6) among 100 genes with higher importance scores. qRT-PCR analysis confirmed the significant upregulation of these genes in breast cancer patients compared to normal samples. Conclusions These findings suggest that CACNG4, PKMYT1, EPYC, and CHRNA6 may serve as valuable biomarkers for breast cancer diagnosis, and PKMYT1 may also have prognostic significance. Furthermore, CACNG4, CHRNA6, and PKMYT1 show promise as potential therapeutic targets. These findings have the potential to advance diagnostic methods and therapeutic approaches for breast cancer.

Original article Objective(s): N-myc downstream regulated gene 2 (NDRG2) is a candidate gene for ... more Original article Objective(s): N-myc downstream regulated gene 2 (NDRG2) is a candidate gene for tumor suppression. The expression of NDRG2 is down-regulated in several tumors including lung cancer. The aim of this study was to explore the effect of NDRG2 overexpression on invasion, migration, and enzymatic activity of matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) in human lung adenocarcinoma A549 cells. Materials and Methods: A recombinant plasmid encoding green fluorescent protein (GFP)-tagged NDRG2 (pCMV6-AC-NDRG2-GFP) was used to overexpress GFP-tagged NDRG2 in A549 cells. The cells in the experimental group and those in the control group were transfected with pCMV6-AC-NDRG2-GFP and a control plasmid without NDRG2 (pCMV6-AC-GFP), respectively. Fluorescent microscopy and flowcytometry analysis of GFP expression were used to evaluate the cellular expression of GFP-tagged NDRG2 and the efficiency of transfection. The effects of NDRG2 expression on cell invasion and migration were evaluated using transwell filter migration assay. The gelatinase activity of secreted MMP-2 and MMP-9 was measured by gelatin zymography. Results: Our results demonstrated the expression of GFP-tagged NDRG2 in the cytoplasm and nucleus of A549 cells. The findings of transwell assay showed that NDRG2 overexpression reduced migration and invasion of A549 cells compared to control cells. Gelatin zymography analyses revealed that NDRG2 overexpression decreased the gelatinase activity of secreted MMP-2 and MMP-9. Conclusion: These findings suggest that NDRG2 may be a new anti-invasion factor in lung cancer that inhibits MMPs activities.

Scientific Reports

Leishmaniasis is one of the main infectious diseases worldwide. In the midst of all the different... more Leishmaniasis is one of the main infectious diseases worldwide. In the midst of all the different forms of the disease, Cutaneous Leishmania (CL) has the highest incidence in the world. Many trial vaccines have been developed with the purpose of generating long-term cell-mediated immunity to Leishmania(L) major. As there is not any multi-epitope DNA vaccine with high efficacy against L.major, the aim of this study is to design a new multi-epitope DNA vaccine in order to have effective control upon this infectious disease through the immune bioinformatics. The L.major antigens: Gp63, LACK, TSA, LmSTI1and KMP11 were selected to design a multi-epitope DNA vaccine. The initial structure of the DNA vaccine was designed, benefiting from Gen Bank's website information. Epitopes of MHC-I antigens were predicted through the Immune Epitope Database (IEDB), and the selected epitopes were used to make vaccines construct along with linkers. New multi-epitope vaccine including 459 nucleic aci...

Applied Biochemistry and Biotechnology, 2016

Breast cancer is the most common malignancy in women. Altered expression of MUC18, a cell surface... more Breast cancer is the most common malignancy in women. Altered expression of MUC18, a cell surface receptor, and its interaction with Wnt-5a as its ligand, affects the motility and invasiveness of breast cancer cells. In this study, we explored the Wnt-5a binding site and designed an antigenic epitope on the MUC18 receptor using in silico methods. A specific single-chain variable fragment (scFv) was isolated against the epitope by several panning processes. The binding ability of the scFv to the related epitope was evaluated in ELISA and flow cytometry. The inhibitory effects of the selected scFv on MUC18 positive cell line, MDA-MB231, was assessed by migration and invasion assays. The results demonstrated isolation of specific scFv with frequency of 40 % which showed significant binding with the epitope in both ELISA and fluorescence-activated cell sorting (FACS) analyses. The antibody inhibited the migration (76 %) and invasion (67 %) of MUC18 positive cell line. The results suggest the specific anti-MUC18 scFv as an effective antibody for breast cancer immunotherapy.

European Journal of Inflammation

Objectives: The development of effective targeted therapy and drug-design approaches against the ... more Objectives: The development of effective targeted therapy and drug-design approaches against the SARS-CoV-2 is a universal health priority. Therefore, it is important to assess possible therapeutic strategies against SARS-CoV-2 via its most interaction targets. The present study aimed to perform a systematic review on clinical and experimental investigations regarding SARS-CoV-2 interaction targets for human cell entry. Methods: A systematic search using relevant MeSH terms and keywords was performed in PubMed, Scopus, Embase, and Web of Science (ISI) databases up to July 2021. Two reviewers independently assessed the eligibility of the studies, extracted the data, and evaluated the methodological quality of the included studies. Additionally, a narrative synthesis was done as a qualitative method for data gathering and synthesis of each outcome measure. Results: A total of 5610 studies were identified, and 128 articles were included in the systematic review. Based on the results, s...

Iranian journal of pharmaceutical research, 2017

Many cardiovascular diseases may require lifelong anticoagulation therapy. Warfarin is the most p... more Many cardiovascular diseases may require lifelong anticoagulation therapy. Warfarin is the most prescribed medication in this regard with serious side effects in some patients. Several single nucleotide polymorphisms (SNPs) affecting cytochrome P450 system can impact on warfarin metabolism and dosing. 230 cardiovascular patients have participated in the study. The INR levels were 1.5 to 3.5 with a mean range of 2.8. The subjects were divided into two case and control groups. The rs2108622 SNP of the CYP4F2 gene and its effect on warfarin dose requirements in these patients was evaluated.The results of our study showed a correlation between age and warfarin dosage. The overall frequency of the CC and TT allele of rs2108622 was 53.1% and 18.6%. Daily average dose of warfarin in CC, CT and TT variants was 3.5 ± 1.6, 4.5 ± 2.1 and 5.3 ± 2.1 respectively. The daily warfarin dose in patients with CC allele was significantly lower than that for CT or TT. The patients with TT allele required a 1.8 mg/day higher dose of warfarin than that of CC.While there are many studies regarding relation of age and warfarin dose, however, there are contradictory results about pharmacogentic status and warfarin dose in different ethnics. Our study demonstrates that polymorphism in the CYP4F2 rs2108622 has a significant impact on the warfarin requirements in Iranian patients.

Life sciences, 2020

AIMS GnRH-DFF40 (gonadotropin releasing hormone-DNA fragmentation factor 40) humanized recombinan... more AIMS GnRH-DFF40 (gonadotropin releasing hormone-DNA fragmentation factor 40) humanized recombinant immunotoxin serves as a prospective candidate for targeted therapy of malignancies with over-expressed gonadotropin releasing hormone receptor (GnRHR). In this study, we attempted to generate a GnRH-based chimeric protein composed of human DFF40 fused with GnRH which encodes an apoptotic nuclease and specifically targets cancer cells displaying GnRH receptor overexpression. MATERIALS AND METHODS A codon optimized, synthetic GnRH-DFF40 fusion gene and its single counterpart (DFF40) were constructed in pET28a expression vector. Cytotoxicity of these expressed proteins were evaluated on three breast cancer cell lines (MCF7, MDA-MB231, and SKBR3). The stability and biological activity of the recombinant proteins were investigated in the treated cell line and cell-free system. Also, the ability of this fusion and its single form in inducing apoptosis, and inhibiting metastasis and migration...

Complementary Therapies in Medicine

AIMS The objective of the present study was to perform a systematic review and meta-analysis on r... more AIMS The objective of the present study was to perform a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effects of Nigella sativa L. supplementation on the circulating inflammatory and oxidative stress markers, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total antioxidant capacity (TAC) and malondialdehyde (MDA). METHODS Systematic search was performed up to March 2020 using PubMed, Scopus, and ISI web of science databases. Two reviewers independently assessed study eligibility, extracted data, and evaluated methodological quality of included primary studies. Statistical heterogeneity was assessed using I-square (I2) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as the summary effect size. RESULTS Twelve trials were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that Nigella sativa supplementation significantly reduced CRP (SMD: -0.35; 95% CI: -0.59, -0.12, P < 0.001, I2 = 10.5%) and MDA concentrations (SMD: -0.56; 95% CI: -0.98, -0.15, P < 0.001, I2 = 64.7%). Moreover, Nigella sativa supplementation increased TAC (SMD: 0.48; 95% CI: 0.09, 0.87, P = 0.01, I2 = 65.6%) levels; however, it did not affect TNF-α (SMD: -0.35; 95% CI: -0.70, 0.01, P = 0.05, I2 = 58.2%). CONCLUSION Nigella sativa supplementation is associated with improved inflammation and oxidative status. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.

International Immunopharmacology

&NA; Isolation of specific single chain antibodies (scFvs) against key epitopes of cancer mar... more &NA; Isolation of specific single chain antibodies (scFvs) against key epitopes of cancer markers are applied for cancer immunotherapy and diagnosis. In this study following the prediction of the 3D structure of the DSP part of Dentin sialophosphoprotein (DSPP), the epitope was chosen using in silico programs. Panning process was applied to isolate specific human scFv against the epitope. PCR and DNA fingerprinting differentiated the specific clones, which were evaluated by phage ELISA. Following DNA sequencing, the 3D structure of isolated scFv was modeled and Docked on DSP. Results demonstrated the selection of a specific anti‐DSPP scFv with 40% frequency, which reacted significantly with the predicted epitope and PCa patients' urines in ELISA tests (P‐value < 0.05). The VH and VL of the isolated scFv were from VH1 and VL3 gene families with several amino acid changes in CDRs and FRs domains. The scFv tightly bound to the DSP epitope with the lowest energy level by hydrogen bonds, cation‐pi, hydrophobic and ionic interactions demonstrating the specificity of Ag‐Ab interactions. The anti‐DSPP scFv selected in this study with significant specificity to DSPP antigen offers a promising new agent for both PCa early detection and treatment of cancers with DSPP expression.

Iranian Journal of Basic Medical Sciences

Objective(s): Development of new antibodies with broad activity would provide anti-influenza prop... more Objective(s): Development of new antibodies with broad activity would provide anti-influenza prophylaxis and treatment. Human single-chain variable fragments (scFvs) are considered effective agents against viruses. In this study specific human scFvs against highly conserved epitopes in the hemagglutinin (HA) of influenza A viruses were selected and their neutralizing activity was evaluated. Materials and Methods: Bioinformatic methods were used to evaluate HA epitopes. The panning process selected specific clones from a scFv library. PCR and DNA fingerprinting differentiated the common patterns. Soluble forms of scFvs were produced and evaluated using Western blot analysis. The neutralizing effects of anti-HA scFvs were assessed by microneutralization assay using MDCK cells. Real-time PCR was done to determine the exact copy number of the virus following neutralization. Results: Bioinformatic evaluation confirmed the antigenicity and accessibility of the epitopes. Four specific anti...

Objective(s): N‐myc downstream regulated gene 2 (NDRG2) is a candidate gene for tumor suppression... more Objective(s): N‐myc downstream regulated gene 2 (NDRG2) is a candidate gene for tumor suppression. The expression of NDRG2 is down‐regulated in several tumors including lung cancer. The aim of this study was to explore the effect of NDRG2 overexpression on invasion, migration, and enzymatic activity of matrix metalloproteinase‐2 (MMP‐2) and ‐9 (MMP‐9) in human lung adenocarcinoma A549 cells. Materials and Methods: A recombinant plasmid encoding green fluorescent protein (GFP)‐tagged NDRG2 (pCMV6‐AC‐NDRG2‐GFP) was used to overexpress GFP‐tagged NDRG2 in A549 cells. The cells in the experimental group and those in the control group were transfected with pCMV6‐AC‐NDRG2‐ GFP and a control plasmid without NDRG2 (pCMV6‐AC‐GFP), respectively. Fluorescent microscopy and flowcytometry analysis of GFP expression were used to evaluate the cellular expression of GFP‐tagged NDRG2 and the efficiency of transfection. The effects of NDRG2 expression on cell invasion and migration were evaluated using transwell filter migration assay. The gelatinase activity of secreted MMP‐2 and MMP‐9 was measured by gelatin zymography. Results: Our results demonstrated the expression of GFP‐tagged NDRG2 in the cytoplasm and nucleus of A549 cells. The findings of transwell assay showed that NDRG2 overexpression reduced migration and invasion of A549 cells compared to control cells. Gelatin zymography analyses revealed that NDRG2 overexpression decreased the gelatinase activity of secreted MMP‐2 and MMP‐9. Conclusion: These findings suggest that NDRG2 may be a new anti‐invasion factor in lung cancer that inhibits MMPs activities. ►Please cite this article as: Faraji SN, Mojtahedi Z, Ghalamfarsa Gh, Takhshid MA. N‐myc downstream regulated gene 2 overexpression reduces matrix metalloproteinase‐2 and ‐9 activities and cell invasion of A549 lung cancer cell line in vitro. Iran J Basic Med Sci 2015; 18:773‐779.