Molecular Biology Research Communications最新文献

The present study aims to identify the differentially expressed genes in HIGK treated with Fusobacterium nucleatum (Fn) and their possible role in establishing head and neck squamous cell carcinoma. The study design follows a computational approach wherein multiple databases and tools are used to derive the possible association between Fn exposure and the development of HNSCC. The GEOmnibus dataset GSE6927 provided data on the differentially expressed genes in the HIGK treated with Fn. The GEO2R analysis revealed 22 differentially expressed genes in HIGK cells treated with Fn. The expression profile of these genes was then analyzed in the HNSCC (TCGA, Firehose Legacy) dataset employing the UALCAN database. The present study revealed 5 genes viz., GSDMD, NUP214, ZNF426, FUT2, and SERPINB2 exhibiting similar expression patterns in Fn-treated HIGK and HNSCC datasets. The GSDMD and NUP214 were found to be upregulated, and the genes ZNF426, FUT2, and SERPINB2 were downregulated. Among the five genes, the ZNF426 demonstrated a significant association with the survival of HNSCC patients. The low expression of ZNF426 presented a poor prognosis compared to the high expression. The study's results identified ZNF426 as a candidate gene involved in Fusobacterium nucleatum infection and HNSCC. Validating this result is necessary to gain insights into the role of the ZNF426 gene in developing HNSCC. Furthermore, probing the epigenetic factors targeting ZNF426 can be a potential therapeutic lead.

The expression level of exosomal long non-coding RNAs (lncRNAs) can be relevant for clinical diagnostic approaches. The object of our study was to evaluate the differential expression of lncRNAs colon cancer associated transcript 1 (CCAT1) and X-inactive specific transcript (XIST) in plasma exosomes of colorectal cancer (CRC) patients and investigate their potential as clinical biomarkers. In a case-control study, 62 CRC patients and 62 healthy persons were studied. Plasma exosomes were isolated by a centrifugation approach and were characterized by microscopy and western blotting. After RNA extraction and cDNA synthesis, using real-time PCR technique, the relative expression of lncRNAs was evaluated. The expression levels of lncRNA CCAT1, but not XIST, were meaningfully increased in the plasma-derived exosomes of CRC patients compared to non-cancer individuals (p= 0.001, 0.083 respectively). Further analyses revealed that the expression levels of exosomal lncRNA CCAT1 were associated with the lymphovascular invasion and tumor differentiation (p<0.05). ROC curve analysis documented a diagnostic power for lncRNA CCAT1 in CRC with a sensitivity of 79% and a specificity of 80% with an optimal cutoff point 6.5, with an area under curve (AUC)=86% and p<0.0001. Also, lncRNA XIST revealed a sensitivity of 62% and a specificity of 61% with a cutoff point 2.4, with an AUC=65%. Our findings indicated the potential of plasma-derived exosomal lncRNA CCAT1 as a non-invasive clinical indicator for the diagnosis of CRC patients.

Diabetes mellitus has been linked to an increased risk of oral cancer, with hyperglycemia and chronic inflammation contributing to malignant transformation. Accumulating evidence has highlighted the role of specific genes and biomarkers associated with the process. While hyperglycemia accelerates cancer progression, Metformin, an anti-diabetic medication, is found to reduce the recurrence. Future research should focus on understanding molecular mechanisms, developing early diagnostic tools, and assessing the impact of glycemic control in managing potentially oral malignant lesions in diabetic patients.

Cervical cancer is one of the common types of cancer in women. Treatment regimens include use of chemotherapy but it leads to certain side effects thereby creating a need for safer therapeutic options. Ayurveda has a great potential to provide better treatment strategies. In this study, computational approaches have been employed to investigate the molecular mechanism of anti-cervical cancer Ayurvedic herbs. Initially, Ayurvedic plants possessing anti-cervical cancer activities were obtained from literature. Bioactive compounds present in such plants were evaluated for drug-likeliness, biological functions and associations with cancer-related pathways. This resulted in the most promising drug-like bioactive compounds which were found to target cancer pathways like microRNA and proteoglycans, Human papillomavirus infection. Anti-cervical cancer activity possessing herbs derived from the study include Camellia sinensis, Equisetum arvense, Rosmarinus officinalis. Major bioactive compounds extracted from the enlisted herbs that contribute in promoting anti-cervical cancer effects include allicin, apigenin, and mataresinol. Overall, our study has provided insights into the scientific mechanism behind anti-cervical cancer activities of the indigenous herbs of Ayurveda. In addition, this study has also highlighted key bioactive compounds which have a potential in targeting cancer related pathways and thus can further be utilized to devise better therapeutics to cure cervical cancer.

Genetic polymorphisms in interleukin-13 (IL13) gene have been associated with asthma susceptibility in different ethnicities. We investigated the association of two polymorphisms in the IL13 gene [rs1800925 (c.-93+487C>T), and rs20541 (p.Gln144Arg)] with asthma susceptibility among Sudanese patients. A case-control study was conducted at Al-Shaab Teaching Hospital between April and October 2022. Involving fifty asthmatic patients and fifty controls. The genotypes were determined using an allele-specific polymerase chain reaction. For rs1800925, a significant association with asthma in multivariate analysis (aOR=3.15, 95% CI: 1.13-8.76; p=0.028). The T allele was the most frequent in cases and showed a significant association with asthma (aOR=1.99, 95% CI: 1.13-3.5; p=0.016). The rs20541 did not show any association with asthma. The rs1800925 is associated with an increased risk of asthma in Sudanese patients.

Pseudomonas syringae is a gram-negative bacterium that causes a diversity of diseases in numerous plants. Strategies to inhibit P. syringae growth include protective procedures; however, controlling the disease is complicated due to its rapid spread. Several antimicrobial agents can prevent this disease, such as chemical compounds, biological agents, secondary metabolites, nanoparticles, bacteriophages, and antimicrobial peptides (AMPs). The most effective way to control the disease is through chemical control. Using copper compounds and antibiotics is a conventional practice to decrease canker disease symptoms. However, due to environmental pollution caused by chemicals and bactericides and the resistance of different pathovars of P. syringae, other methods for bacterial pathogens control are needed. Biological control, using antagonistic bacteria has shown promising results against P. syringae under in vitro conditions. New studies focus on using secondary metabolites from plants to control plant diseases. Studies have shown that essential oils when preserved from degradation and evaporation by nanoparticles like mesoporous silica, can increase their antibacterial activities. Using nanoparticles, especially silver, is a suitable strategy for controlling P. syringae. However, high concentrations of silver nanoparticles are toxic. Bacteriophages and AMPs are recommended as alternatives to control bacterial infections in agriculture, including P. syringae. Combined treatments of phages and secondary metabolites have shown higher efficacy, potentially overcoming resistance. However, bacteriophages and AMPs are expensive and limited. In the end, using secondary metabolites and nanoparticles at low concentrations presents economic benefits and antibacterial activities without phytotoxic properties.

Acute myeloid leukemia (AML) is the most frequent type of leukemia among adults. Investigating AML heterogeneity based on DNA methylation can improve clinical diagnosis and prognosis. This study was conducted to investigate NR4A1 and NR4A3 gene methylation in fifty newly diagnosed AML patients and fifty healthy controls using Methyl specific PCR (MSP). The frequency of the rs1569686 in the DNMT3B was also determined by Tetra primer ARMS PCR. Also, the association between methylation of studied genes and some prognostic marker including mutation of FLT3 and NPM genes, as well as some hematological factors of patients was evaluated. According to the findings, AML patients have a significantly higher prevalence of methylated NR4A1 and NR4A3 genes than those without AML. AML patients with un-methylated NR4A3 had significantly higher frequency of FLT-ITD positivity than AML patients with methylated NR4A3. Also, there was no significant association between rs1569686 and AML. Finally, the distribution of different genotypes of rs1569686 between AML patients with and without methylation in NR4A1 and NR4A3 did not show any significant association. The results found that NR4A1 and NR4A3 were hyper-methylated in AML patients. However, rs1569686 polymorphism was not a main contributor to methylation status of studied gene. Future studies should consider other mechanisms influencing the role of NR4A1 and NR4A3 hypermethylation in AML.

Chinese Hamster Ovary (CHO) cells are essential in biopharmaceutical manufacturing. Scientists use CRISPR to enhance productivity. mRNAs contain UTRs that regulate gene expression, affecting protein abundance. Targeting these regions creates desirable knockout cells. The Caspase 8 Associated Protein 2 (CASP8AP2) gene is a promising target for improving host cell viability. This study used the CRISPR-Homology-Independent Targeted Integration (HITI) strategy to modify the 3'UTR region of the CASP8AP2 gene in CHO cells. The aim was to evaluate the effects of CASP8AP2 silencing on cell proliferation, viability, apoptosis, and the cell cycle. CASP8AP2 silencing was assessed post-modification by extracting genomic DNA from modified and unmodified CHO cells, followed by PCR and sequencing to confirm deletions. Cell proliferation and viability were measured using MTT assays, and cell cycle analysis was performed via flow cytometry. Apoptosis was evaluated through Annexin V/PE staining and flow cytometry, with apoptosis resistance assessed by determining the IC₅₀ of sodium butyrate. Results showed CASP8AP2 deletion did not affect cell proliferation or the cell cycle but improved CHO cell viability and increased resistance to apoptosis. The IC₅₀ for sodium butyrate was higher in CASP8AP2 knockout cells (7.84 mM) compared to native cells (3.43 mM), indicating enhanced apoptosis resistance. This study highlights CASP8AP2's role in apoptosis regulation without impacting cell proliferation or the cell cycle. CASP8AP2 deletion enhances viability and resistance to apoptosis, suggesting it as a target for improving recombinant protein production. Further research is needed to elucidate the molecular mechanisms and develop therapeutic strategies based on this approach.

Testis specific gene antigen 10 (TSGA10) is a protein which has roles in spermatogenesis and cancers so that deletion or mutation in the TSGA10 gene resulted in non-obstructive infertility and aberrant expression of this protein, was detected in solid tumors and leukemia. Despite the crucial roles of TSGA10 in tumorigenesis and infertility, yet it is not obvious how various nsSNPs of its gene impress the structure and function of the TSGA10. Therefore, it is worthwhile to investigate the potential highly deleterious nsSNPs by several in-silico tools before launching costly experimental approaches. In the current study, we employed several different machine learning algorithms in a two-step screening procedure to analyze single nucleotide substitutions of TSGA10 gene. Prediction tools were included SIFT, PROVEAN, PolyPhen-2, SNAP2, SNPs & GO, PhD-SNP for the first step and the second step included predictive tools such as I-mutant 3.0, MUpro, SNPeffect 4.0 (LIMBO, WALTZ, TANGO, FoldX), MutationTaster and CADD. Also, the 3D models of significantly damaging variants were built by Phyre2. The results elucidated 15 amino acid alterations as the most deleterious ones. Among these S563P, E578K, Q580P, R638L, R638C, R638G, R638S, L648R, R649C, R649H were located in a domain which is approved to has interaction with the HIF1-A protein and D62Y, R105G, D106V and D111Y were located on phosphodiesterase domain. In sum, these predicted mutations significantly influence the function of TSGA10 and they could be used for precise study of this protein in infertility and cancer experimental investigations.