Helicobacter pylori, a significant factor in the development of gastric cancer and peptic ulcers, poses challenges for drug development due to its resilience. Computational approaches offer potential solutions for effective vaccine development targeting its antigens while ensuring stability and safety. The four critical antigenic proteins included in this study's innovative vaccine design are neuraminyllactose-binding hemagglutinin (HpaA), catalase (KatA), urease (UreB), and vacuolating toxin (VacA).
View Article and Find Full Text PDFCarboxypeptidase B (CPB) in Anopheles spp. breaks down blood and releases free amino acids, which promote Plasmodium sexual development in the mosquito midgut. Our goal was to computationally assess the inhibitory effectiveness of carboxypeptidase inhibitors obtained from tomato, potato (CPiSt), and leech against the Anopheles stephensi CPBAs1 and CPBAs2 enzymes.
View Article and Find Full Text PDFPurpose: Cancer testis antigens (CTAs) are a family of proteins typically expressed in male testicles but overexpressed in various cancer cell types. Transmembrane Phosphatase with Tensin homology (TPTE) is expressed only in the testis of healthy individuals and is a member of the family of CTAs. The current study, for the first time, examined the significance of TPTE expression in prostate cancer (PCa) tissues by generating a novel antibody marker targeting TPTE protein.
View Article and Find Full Text PDFThe lack of effective medicines or vaccines, combined with climate change and other environmental factors, annually subjects a significant proportion of the world's inhabitants to the risk of dengue virus (DENV) infection. These conditions increase the likelihood of exposure to mosquito-borne diseases such as dengue fever. Hence, many research approaches tend to develop efficient vaccine candidates against the dengue virus.
View Article and Find Full Text PDFIn the present study, we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells. Myc decoy ODNs were designed based on the promoter of gene and analyzed by molecular docking and molecular dynamics assays. ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.
View Article and Find Full Text PDFOver-expression of K+ channels has been reported in human cancers and is associated with the poor prognosis of several malignancies. EAG1, a particular potassium ion channel, is widely expressed in the brain but poorly expressed in other normal tissues. Kunitz proteins are dominant in metazoan including the dog tapeworm, Echinococcus granulosus.
View Article and Find Full Text PDFBackground: Methylmalonic acidemia (MMA) is a rare metabolic disorder resulting from functional defects in methylmalonyl-CoA mutase. Mutations in the MMAB gene are responsible for the cblB type of vitamin B12-responsive MMA.
Results: This study used Whole-exome sequencing (WES), Sanger sequencing, linkage analysis, and in-silico evaluation of the variants' effect on protein structure and function to confirm their pathogenicity in a 2-day-old neonate presenting an early-onset metabolic crisis and death.
Keratinocyte growth factor (KGF) is a potential therapeutic factor in wound healing. However, its applications have been restricted due to its low stability, short half-life, and limited target specificity. We aimed to immobilize KGF on collagen-based biomaterials for long-lasting and targeted therapy by designing fusion forms of KGF with collagen-binding domains (CBD) from natural origins.
View Article and Find Full Text PDFNowadays, mutations in the epidermal growth factor receptor (EGFR) kinase domain are studied in targeted therapy of non-small cell lung cancer (NSCLC) with EGFR tyrosine kinase inhibitors including gefitinib and erlotinib. The present study reports a rare case of a patient harboring three simultaneous EGFR mutations (L718A, Q849H, and L858R). The development of erlotinib resistance was detected in the subsequent treatment.
View Article and Find Full Text PDFSince the onset of the global epidemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whole genome sequencing of virus in all countries has been considered to track and predict virus transmission and variation patterns. In the current study we reported a novel complete genome sequence of SARS-CoV-2 isolated from Iran. Genomics variations and protein sequences were evaluated for the isolated sequence and seven Iranian complete genome sequences of SARS-CoV-2 from NCBI using the reference genome of the SARS-CoV-2 Wuhan-Hu-1.
View Article and Find Full Text PDFOne of the most important challenges in the battle against contagious SARS-CoV-2 is subtle identification of the virus pathogenesis. The broad range of COVID-19 clinical manifestations may indicate diversity of virus-host cells. Amongst key manifestations, especially in severe COVID-19 patients, reduction and/or exhaustion of lymphocytes, monocytes, basophils, and dendritic cells are seen.
View Article and Find Full Text PDFSignal transducer and activator of transcription 3 (STAT3) is a critical regulator for angiogenesis, cell cycle progression, apoptosis, and drug resistance. Resistance toward EGF receptor (EGFR) inhibitors is a significant clinical concern for metastatic colon cancer patients. The present study aimed to evaluate the blocking influences of STAT3 decoy oligodeoxynucleotides (ODNs) on the STAT3 survival signaling pathway in nonresistant and erlotinib-resistant SW480 colon cancer cells.
View Article and Find Full Text PDFRecently, advances in the synthesis and development of multifunctional nanoparticle platforms have opened up great opportunities and advantages for specifically targeted delivery of genes of interest. BSA-coated niosome structures (NISM@B) can potentially improve the efficiency delivery of nucleic acid molecules and the transfection of genes. Few studies have reported the combined use of niosomes with nucleic acid as therapeutic agents or decoy oligodeoxynucleotides (ODNs).
View Article and Find Full Text PDFAberrant activation of Wnt/β-catenin signaling pathway, due to the genetic or epigenetic changes, is responsible for tumorigenesis in epithelial cells of different types of cancer such as colorectal cancer. Secreted Frizzled-Related Protein-1 (SFRP1), as one of the antagonist proteins of this pathway, is hyper-methylated in colorectal cancer leading to the formation of Wnt-Fz-LRP and activation of Wnt/β-catenin signaling pathway. We aimed to design antagonist peptides based on SFRP1 structure against wingless-type 2 (Wnt2), a highly expressed ligand in different cancers like colorectal cancer, to inhibit the formation of the initial triple complex of Wnt-Fz-LRP.
View Article and Find Full Text PDFHepatitis B virus (HBV) is a global virus responsible for a universal disease burden for millions of people. Various vaccination strategies have been developed using viral vector, nucleic acid, protein, peptide, and virus-like particles (VLPs) to stimulate favorable immune responses against HBV. Given the pivotal role of specific immune responses of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infection control, we designed a VLP-based vaccine by placing the antibody-binding fragments of HBsAg in the major immunodominant region (MIR) epitope of HBcAg to stimulate multilateral immunity.
View Article and Find Full Text PDFThe development of bacterial resistance toward antibiotics has been led to pay attention to the antimicrobial peptides (AMPs). The common mechanism of AMPs is disrupting the integrity of the bacterial membrane. One of the most accessible targets for α-defensins human neutrophil peptide-1 (HNP-1) is lipid II.
View Article and Find Full Text PDFPertussis, caused by is still one of the controversial diseases worldwide due to its high prevalence in both the developed and the developing countries, especially among young children. As currently approved vaccines are not protective enough and provide Th2-type immune responses, there is an urgent need to develop new vaccines. In the current study, we applied the C-terminal fragment of enterotoxin (C-CPE) as a delivery system and F1S1 fragment (Filamentous hemagglutinin (F1) and subunit 1 of pertussis toxin (S1) of to design a novel chimeric protein , to target Claudin-4 receptors in mice lung cells.
View Article and Find Full Text PDFBackground: According to scientific recommendations, paratransgenesis is one of the solutions for improving the effectiveness of the Global Malaria Eradication Programme. In paratransgenesis, symbiont microorganisms are used for distorting or blocking the parasite life-cycle, affecting the fitness and longevity of vectors or reducing the vectorial competence. It has been revealed recently that bacteria could be used as potent tools for double stranded RNA production and delivery to insects.
View Article and Find Full Text PDFDue to the presence of cancer stem cells (CSCs), breast cancer often relapsed after conventional therapies. Strategies that induce differentiation of CSCs will be helpful in eradication of tumor cells, so we designed an oligodeoxynucleotide (ODNs) for targeting of signal transducer and activator of transcription 3 (STAT3) transcription factor which is involved in stemness, and constitutively activated in triple-negative breast cancer. Molecular docking and electrophoretic mobility shift assay analysis showed that decoy ODN bound specifically to the DNA binding site of STAT3 protein.
View Article and Find Full Text PDFExpression of master transcriptional regulators of stem cells (Oct4 and Sox2) is associated with mediating tumor proliferation and tumor differentiation. The main goal of this study is the investigation of specific binding of designed Oct4-Sox2 transcription factors decoy oligodeoxynucleotides (ODNs) sequence to their nucleus-extracted proteins in HT29-ShE cells containing enriched cancer stem-like cells (SCLCs). First, gene expression of Oct4, Sox2, and E-cadherin revealed the overexpression of Oct4 and Sox2 and downregulation of E-cadherin in HT29-ShE cells compared with HT29 wild-type and HT29-ShC cells.
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