Association between colorectal cancer, the frequency of Bacteroides fragilis, and the level of mismatch repair genes expression in the biopsy samples of Iranian patients.

BACKGROUND: Deficient DNA mismatch repair (MMR) can cause microsatellite instability (MSI) and is more common in colorectal cancer (CRC) patients. Understanding the carcinogenic mechanism of bacteria and their impact on cancer cells is crucial. Bacteroides fragilis (B. fragilis) has been identified as a potential promoter of tumorigenesis through the alteration of signaling pathways. This study aims to assess the expression levels of msh2, msh6, mlh1, and the relative frequency of B. fragilis in biopsy samples from CRC patients. MATERIALS AND METHODS: Based on the sequence of mlh1, msh2, and msh6 genes, B. fragilis specific 16srRNA and bacterial universal 16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: Significant increases in the expression levels of mlh1, msh2, and msh6 genes were observed in the cancer group. Additionally, the expression of these MMR genes showed a significant elevation in samples positive for B. fragilis presence. The relative frequency of B. fragilis in the cancer group demonstrated a significant rise compared to the control group. CONCLUSION: The findings suggest a potential correlation between the abundance of B. fragilis and alterations in the expression of MMR genes. Since these genes can play a role in modifying colon cancer, investigating microbial characteristics and gene expression changes in CRC could offer a viable solution for CRC diagnosis.

Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases.

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. Video Abstract.

Association between colorectal cancer and expression levels of miR-21, miR-17-5P, miR-155 genes and the presence of Fusobacterium nucleatum in biopsy samples obtained from Iranian patients.

BACKGROUND: Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC. METHOD: DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group. CONCLUSION: Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes.

Isolation and Chemical Characterization of an Alpha-Helical Peptide, Dendrocin-ZM1, Derived from Zataria multiflora Boiss with Potent Antibacterial Activity.

Today, resistance of microorganisms to antibiotics has become a major challenge. To overcome this problem, development of new drugs, besides research on their antibacterial activity, is essential. Among chemical components, antimicrobial peptides (AMPs) exhibit antibacterial activity and can be selected as suitable antimicrobial candidates. In this study, a novel antimicrobial peptide, called dendrocin-ZM1, with a molecular weight of ~3716.48 Da, was isolated from Zataria multiflora Boiss (ZM) and purified via precipitation with ammonium sulfate and reverse-phase HPLC chromatography; it was then sequenced via Edman degradation. The in silico method was used to examine the physicochemical properties of dendrocin-ZM1. In this study, four reference strains (gram-positive and gram-negative) and one clinical vancomycin-resistant Staphylococcus aureus strain were used to survey the antimicrobial activities. Moreover, to examine cytotoxicity and hemolytic activity, a HEK-293 cell line and human red blood cells (RBCs) were used, respectively. Evaluation of the physicochemical properties of dendrocin-ZM1, as an AMP, indicated a net charge of + 7 and a hydrophobicity percentage of 54%. This peptide had an amphipathic alpha-helical conformation. It exhibited broad-spectrum antibacterial activities against the tested strains at minimum inhibitory concentrations (MICs) of 4-16 µg/mL. Besides, this peptide showed negligible hemolysis and cytotoxicity in the MIC range. It also exhibited heat stability at temperatures of 20 to 80 °C and was active in a broad pH range (from 6.0 to 10.0). Overall, the present results suggested dendrocin-ZM1 as a remarkable antimicrobial candidate.

Proliferative Effect of FadA Recombinant Protein from Fusobacterium nucleatum on SW480 Colorectal Cancer Cell Line.

BACKGROUND AND AIM: Colorectal Cancer (CRC) is one of the most frequent cancers diagnosed in both men and women worldwide. Fusobacterium nucleatum adhesin A (FadA) has an important potential factor in the development or progression of CRC. The aim of the present study was to evaluate the proliferative effect of recombinant FadA on SW480 colorectal cancer cell line. MATERIALS AND METHODS: The recombinant pET21(b)-fadA plasmid was synthesized and transformed into competent E.coli DH5α. In the next step, induction and expression of recombinant FadA were carried out in E. coli BL21 (DE3) competent cells. Expression and purification of protein were successfully done and it was analyzed and confirmed by SDS-PAGE and western blotting. The proliferative effect of purified FadA on SW480 CRC cell line was evaluated using MTT assay and cell counting methods. RESULTS: Visualization of the specific band isolated from the linear plasmid on the agarose gel confirmed the presence of the desired gene. After electrophoresis and Coomassie blue staining, the protein of interest with an approximate molecular weight of 13KDa was detected. The MTT assay, similar to cell counting methods, revealed that FadA dose and time-dependently promoted SW480 cell growth and proliferation in 24, 48 and 72 hours. CONCLUSION: The results showed that FadA stimulates proliferation of SW480 colorectal cancer cell line with a dose and time-dependent manner.