Shiraz University PressMolecular Biology Research Communications2322-181X13420241201In-silico comparison of fungal and bacterial asparaginase enzymes183191750810.22099/mbrc.2024.50123.1981ENNegarTafviziDepartment of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranMandanaBehbahaniDepartment of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranHassanMohabatkarDepartment of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, IranJournal Article20240505L-asparaginase is a commercial enzyme with a wide variety of applications. Asparaginase is known as an anti-cancer agent that is effective for the treatment of certain lymphomas and leukemias by growth inhibition of human cancer cells. Additionally, asparaginase is used in the food industry in a pretreatment process to decrease the accumulation of carcinogenic acrylamide. In this paper, different aspects of bacterial and fungal asparaginases such as mass, hydrophobicity and hydrophilicity of pseudo amino acid composition (PseAAC), physicochem<em>-</em>ical properties, and structural motifs were studied, and ROC curve statistical analysis was used for the comparison. The results showed that none of the physicochemical properties of fungal and bacterial asparaginase could not be differed, except molecular weight and sequence length. MEME Suite analysis demonstrated that there was a motif that was specific for bacterial asparaginases. However, analysis based on the concept of PseACC indicated a differentiation line between fungal and bacterial asparaginases. In conclusion, although there was not any specific demonstration to separate the bacterial and fungal asparaginases in the case of physicochemical properties, PseAAC analysis can be an appropriate and usable method to differentiate between them.https://mbrc.shirazu.ac.ir/article_7508_a71d0095595e01786722dea90b865e1e.pdfShiraz University PressMolecular Biology Research Communications2322-181X13420241201The hepatoprotective effects of sitagliptin against cyclophosphamide-induced hepatotoxicity in rat193200750910.22099/mbrc.2024.49925.1964ENRezaMalekiDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, IranMohammad FoadNoorbakhshDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, IranNasrinKazemipourDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, IranMaliheMasudianMolecular Department of Central Laboratory, School of Veterinary Medicine, Shiraz University, Shiraz, IranFatemehNamaziDepartment of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IranSaeedNazifiDepartment of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, IranJournal Article20240409Hepatotoxicity is a serious side effects of cyclophosphamide. Thus, the present research investigates the protective properties of sitagliptin against cyclophosphamide-induced hepatotoxicity. Fifty male rats were randomly divided into five groups. They were pre-treated with either sitagliptin or normal saline once a day for the first ten days of the study. To induce acute hepatotoxicity, cyclophosphamide (200 mg/kg, i.p) was injected only one time and 45 min after the last dose of sitagliptin. The rats were sacrificed on the 11th day, and their blood and liver were collected for biochemical, gene expression, and histopathological assessments. Our results showed that cyclophosphamide induced obvious liver toxicity as marked by an increase in serum levels of alanine transaminase and aspartate transaminase, reduced serum albumin and total protein levels, in addition to histopathological changes. The malondialdehyde, tumor necrosis factor-, and interleukin-6 levels were also elevated and total antioxidant capacity declined in serum and hepatic homogenates. Sitagliptin magnificently attenuated the cylophosphamide-induced histological alterations, improved liver function tests, enhanced total antioxidant capacity, and decreased malondialdehyde, tumor necrosis factor-α, and interleukin-6 in the blood and hepatic tissues. These findings suggest that sitagliptin has hepatoprotective activity against cyclophosphamide toxicity, which may be due to its antioxidant and anti-inflammatory effects.https://mbrc.shirazu.ac.ir/article_7509_9a41d8247e32b121f307a762bf21c57f.pdfShiraz University PressMolecular Biology Research Communications2322-181X13420241201Down-regulation of key regulatory factors in sphingosine-1-phosphate (S1P) pathway in human lung fibroblasts transfected with selected microRNAs201209755210.22099/mbrc.2024.49810.1951ENAbdolamirAllamehDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranMostafaAtashbastehDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranEsmaeilMortazDepartment of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranBaharehNaeeniDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranMajidJafari-KhorchaniDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranJournal Article20240324Sphingosine 1 phosphate (S1P) is involved in the pathogenesis of asthma by stimulation of the alpha-smooth muscle actin (SMA) expression and remodeling of fibroblasts. This study was designed to determine the effects of selected micro RNAs in regulation of S1P and related metabolic pathways in a human lung fibroblast cell line. The fibroblast cell line (CIRC-HLF, C580) was cultured and transfected with individual viral vectors carrying miR124, mi125b, mi133b or mi130a. After 48 hours, expression level of miRNAs and their target genes, sphingosine kinase 1(SPHK1), sphingosine 1-phosphate lyase 1 (SGPL1), sphingosine 1- phosphate receptor 1 (S1PR1) and sphingosine 1- phosphate receptor 2 (S1PR2) were determined. Expression of miRNA and mRNA determined by reverse transcription‑quantitative polymerase chain reaction (qPCR) showed that the expression level of the miRNAs was significantly higher in human lung fibroblasts following transfection compared to controls (vector backbone without miRNA). The expressions of miRNAs-targeted genes were significantly downregulated in transfected fibroblasts compared to control cells (p<0.05). Data show that miR 124, miR 125b, miR 133b and miR130a by targeting regulatory genes in S1P-pathway can down-regulate key factors such as SPHK1, SGPL1, S1PR1 and S1PR2 genes in lung fibroblasts. The results showed that S1P pathway and key factors are suppressed in lung fibroblasts expressing miR124, miR125b, miR130a or miR133b. It appears that suppression of any of the intermediate factors in S1P by miRNA can affect the regulation of the entire S1P pathway.https://mbrc.shirazu.ac.ir/article_7552_b1df95d938cff34520a4c69fad3c64ce.pdfShiraz University PressMolecular Biology Research Communications2322-181X13420241201Comparison of inflammatory molecular mechanisms between osteoarthritis and rheumatoid arthritis via gene microarrays211222755310.22099/mbrc.2024.49924.1963ENMaziarOveiseeOrthopedic Department, Bam University of Medical Sciences, Bam, IranAkramGholipourCardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, IranMahshidMalakootianCardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, IranJournal Article20240409Osteoarthritis (OA) and rheumatoid arthritis (RA) treatment requires exact arthritis type diagnosis. We compared inflammatory molecular mechanisms between OA and RA to introduce reliable molecular biomarkers. The GSE55235 and GSE100786 microarray datasets were acquired from the GEO. Data preprocessing and differential expression analysis were conducted in OA and RA groups and their control groups applying GEO2R. Differentially expressed genes (DEGs) with a |LogFC|>1 and adj. <em>p</em><0.05 were determined. Gene ontology (GO) and signaling pathway analysis were done utilizing PANTHER and Enrichr. The suitability of gene expression alterations as biomarkers was tested using the receiver operating characteristic (ROC) curve analysis. We found 2129 DEGs between the OA and control groups and 2494 DEGs between the RA and control groups. GO on the DEGs showed enrichment in binding, cellular processes, and cellular anatomical entities in molecular functions, biological processes, and cellular components, respectively. Enrichr found the cell differentiation pathways of Th1 and Th2 only in RA. The ROC curve analysis indicated <em>HLA-DQA1</em> downregulation and <em>MAPK8IP3 </em>upregulation as reliable biomarkers to discriminate RA from OA in peripheral blood and bone marrow samples, respectively. We found more DEGs in patients with OA than those with RA and determined inflammatory pathways and genes unique to RA as reliable biomarkers to discriminate RA from OA. Gene expression alterations associated with Th1 and Th2 cell differentiation pathways, including <em>HLA-DQA1 </em>downregulation and <em>MAPK8IP3</em> upregulation, could be novel molecular biomarkers to diagnose RA.https://mbrc.shirazu.ac.ir/article_7553_c3608340eb4ab75637d64fcbfb2e996e.pdfShiraz University PressMolecular Biology Research Communications2322-181X13420241201In silico analysis for SARS-CoV-2 detection in the context of genetic variability of the Algerian omicron variant223234755410.22099/mbrc.2024.50192.1985ENChahinez AmiraDahmaniBiology Department, Faculty of Natural and Life Sciences, University of Mostaganem, AlgeriaLaboratory of Molecular and Cellular Genetics (LGMC), University of Sciences and Technology of Oran, AlgeriaAsmaaAzzouneLaboratory of Molecular and Cellular Genetics (LGMC), University of Sciences and Technology of Oran, AlgeriaHigh School of Biological Sciences, Oran, AlgeriaAbdallahBoudjemaLaboratory of Molecular and Cellular Genetics (LGMC), University of Sciences and Technology of Oran, AlgeriaJournal Article20240513The risk to public health conferred by the Omicron variant is still not completely clear, although its numerous gene mutations have raised concerns regarding its potential for increased transmissibility and immune escape. In this study, we test the compatibility of the different primers and probes available in different commercial kits sold internationally with all the sequences of SARS-CoV-2 analyzed in Algeria until March 2023. The<strong> </strong>Algerian SARS-CoV-2 Omicron variant sequences were aligned with the Muscle tool using Genious software. We also used primers and probes sequences of seven international RT-qPCR kits; CDC China, Charite Germany, HKU Hong Kong, NIH Thailand, NIID Japan, CDC US, and Pasteur Institute. We used the primer check v2.0 developed by VIROSCIENCE LAB, To identify the different mutations located at the level of primers and probes about the Algerian sequences of SARS-CoV2. Statistical tests were carried out by calculating the c<sup>2</sup> test. We found regarding the Forward primer sequences that the two Thailand and Japan kits are less specific to the Algerian version of the SARS-CoV-2 Omicron variant genome compared to the other kits (<em>p</em>=10<sup>-6</sup>). Furthermore, regarding the Reverse primers and fluorescent Probes, the three kits; Thailand, Japan, and CDC US; are less effective (<em>p</em>=10<sup>-6</sup>). Regarding all primers and probes, this work allowed us to conclude that the four RT-qPCR kits: CDC China, Charite Germany, NHD Hong Kong, and Pasteur Institute seem to be more specific for the Algerian omicron genome detection and therefore for diagnosis of COVID-19 in Algeria.https://mbrc.shirazu.ac.ir/article_7554_f03f6386af45251022e698f2d5a2bff0.pdfShiraz University PressMolecular Biology Research Communications2322-181X13420241201A comprehensive in silico analysis of mutation spectrum of maple syrup urine disease (MSUD) genes in Iranian population235246755810.22099/mbrc.2024.49847.1958ENNahidRezaieStudent Research Committee, Golestan University of Medical Sciences, Gorgan, IranSaeedeh SadatGhazanfariMashhad University of Medical Sciences, Mashhad Branch, Islamic Azad University, Mashhad, IranTeymoorKhosraviStudent Research Committee, Golestan University of Medical Sciences, Gorgan, IranFatemehVaghefiStudent Research Committee, Golestan University of Medical Sciences, Gorgan, IranMortezaOladnabiGorgan Congenital Malformations Research Center, Golestan University of Medical Sciences, Gorgan, IranJournal Article20240402Maple syrup urine disease (MSUD) represents an infrequent metabolic disease precipitated by an insufficiency of the enzymatic complex known as branched-chain alpha-keto acid dehydrogenase. MSUD can be classified as classic (severe), intermediate, or intermittent based on the severity of the condition. The disease is associated with mutations in several genes, including <em>BCKDHA</em>, <em>BCKDHB</em>, <em>DBT</em>, and <em>DLD</em>. This study aimed to investigate the genetic landscape of MSUD in Iranian patients and explore the clinical implications of identified gene variants. A comprehensive analysis was conducted using various molecular techniques and bioinformatics tools to predict protein stability, pathogenicity, amino acid conservation, and secondary/tertiary structure. The in silico analysis highlighted high-risk pathogenic variants and provided insights into their potential impact on protein structure and function. Furthermore, the predicted 3D structures of wild-type and mutant proteins elucidated structural differences. Protein-protein interaction analysis shed light on the network of interactions involving MSUD-related proteins. The Iranome database uncovered a potential pathogenic variant (c.554C>T) in the Persian population. This research contributes to a better understanding of MSUD genetics in the Iranian population and outlines potential avenues for further clinical investigations. The findings have implications for genetic testing, prognosis, and genetic counseling in affected families.https://mbrc.shirazu.ac.ir/article_7558_5ddc49284613590ab32af9dc01afff32.pdfShiraz University PressMolecular Biology Research Communications2322-181X13420241201Association between rs3761548 polymorphism of FOXP3 and the risk of gastric cancer: a case-control study247252760610.22099/mbrc.2024.49125.1989ENShamimehValidiDepartment of Biology, Faculty of Science, Shiraz University, Shiraz, IranIrajSaadatDepartment of Biology, Faculty of Science, Shiraz University, Shiraz, IranJournal Article20240520Gastric cancer is one of the most prevalent malignancies in the world. Various factors play a role in the development of this disease as risk factors. One of these genes is the <em>FOXP3</em>, which is located on the short arm of the X chromosome (Xp11.23). The rs3761548 polymorphism in the promoter region of this gene increases cell proliferation. In the current study, the association between this genetic polymorphism and the risk of gastric cancer was investigated. This study included 147 patients (55 women, 92 men) with gastric cancer and 147 healthy individuals (53 women, 94 men). The PCR-RFLP method is used for genotyping. Statistical analysis showed that there was no significant association between this polymorphism and the risk of gastric cancer. However, the analysis of genotype, family history and smoking risk factors simultane-oussly revealed a significant relationship between simultaneous occurrence of two (OR=3.79, 95% CI=1.77-8.09, p=0.001) and three risk factors (OR=6.44, 95% CI=1.76-23.5, p=0.017) and the risk of gastric cancer.https://mbrc.shirazu.ac.ir/article_7606_4736bd874c356df22f321bdc6d4d8024.pdf