Molecular Biology Research Communications最新文献

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

Maple 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 BCKDHA, BCKDHB, DBT, and DLD. 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.

L-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-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.

Herein, a detailed molecular phylogeny analysis was developed to determine the phylogenetic position of a new freshwater histozoic myxosporean cnidarian, Henneguya markiana sp. nov. from the world's largest tropical wetland area, Pantanal, Brazil. The new species is described using an integrative taxonomy approach including morphology, biological traits and molecular data. Phylogenetic analysis inferred by Maximum Likehood method showed the new Henneguya species in a well-supported clade of myxosporean gill parasites of South American characids fishes. In this same clade, the new Henneguya described appeared in a sub-clade clustering with H. lacustris and H. chydadea. Nevertheless, the sequences of the new species and H. lacustris and H. chydadea have a large genetic divergence of 10.4% (148 nucleotides-nt) and 10.5% (147 nt) respectively. To the best of our knowledge, this is the first report of a cnidarian myxosporean species parasitizing a fish from Stevardiinae from South America. In the light of the differences observed from the integrative taxonomy, we are confident that this isolate is a new species of Henneguya, increasing the knowledge of diversity of this enigmatic group of cnidarians.

tRNAs act as adaptors during protein synthesis and are chemically modified post-transcriptionally for their structural stability as well as accuracy of the translation. Hypomodifications of tRNAs are known to cause various human diseases, including cancer. Studies in bacteria and yeasts showed that levels of tRNA modifications vary under different stress conditions, enabling the organism to modulate gene expression for survival. Isopentelylation of the base 37 (i⁶A37) in the anticodon stem-loop by tRNA isopentenyltransferase (MiaA) is well-conserved modification present in prokaryotes and eukaryotes. i⁶A37 modification increases both the speed and fidelity of translation. A homozygous p.Arg323Gln mutation in the tRNA binding region of tRNA isopentenyltransferase reduced i⁶A37 levels in humans, affecting mitochondrial translation and thereby causing neurodevelopmental disorder. In this study, we mutated the Arg residue at the conserved position to Gln in Mycobacterium tuberculosis (M. tb) MiaA and analyzed the i6A modification activity of the enzyme on its target tRNAs. We found that p.Arg274Gln mutant MiaA could not modify the target tRNAs, tRNA^LeuCAA, tRNA^PheGAA, and tRNA^SerCGA from M. tb, confirming the role of Arg residue in tRNA binding.

Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.

Bladder cancer (BC) is a multifactorial disease with a poorly understood main cause. In this study, we aimed to evaluate the effect of the polymorphisms rs2228611 of the DNMT1 gene and rs1569686 of the DNMT3B gene on the susceptibility to develop Bladder Cancer in the Algerian population. A case-control study design was adopted, with DNA samples of 114 BC patients and 123 healthy controls. We found that the rs2228611 of the DNMT1 gene was strongly associated with an increased risk of BC development under genetic models: Codominant AG vs. GG (OR=2.54, 95% CI=1.21-5.51, adj p=0.015) and dominant AA+AG vs. GG (OR=2.24, 95% CI=1.12-4.60, adj p=0.023). However, no statistically significant association was observed between the rs1569686 of the DNMT3B gene and the predisposition to BC. To the best of our knowledge, this is the first peer-reviewed study to evaluate the effect of the rs2228611 polymorphism on bladder cancer occurrence. Our results suggest that the rs2228611 might be a potential biomarker for BC development risk. Additional studies are needed to validate our findings.

Breast cancer is particularly severe in women. Research highlights the crucial role of miRNAs in key cellular processes, showcasing their intricate interactions with the oncogenic PI3K/AKT/mTOR (PAM) signaling pathway and underscoring their significant role as tumor suppressors. The effect of silibinin on cell growth and survival was evaluated using an MTT assay. Bioinformatics analysis identified putative miR-133a targets inside the PAM pathway. After incubating MCF-7 cells with silibinin, we measured miR-133a, EGFR, PI3K, AKT, PTEN, and mTOR expression levels using qRT-PCR. Furthermore, protein expression levels of mTOR were assessed using Western blotting. The MTT experiment displayed that silibinin effectively inhibits MCF-7 cell proliferation in a time- and dose-dependent manner. Silibinin's IC₅₀ value, determined at 370 μM after 48 hours, was established. qRT-PCR analysis at this IC₅₀ concentration highlighted reduced expression of EGFR, PI3K, AKT, PTEN, and mTOR mRNAs, alongside increased miR-133a expression. Notably, miR-133a exhibited a negative correlation with both EGFR and PIK3C2A expression. Furthermore, western blotting confirmed silibinin's capacity to diminish p-mTOR protein levels, the ultimate element of the PAM signaling pathway. The findings enhance comprehension of silibinin's impact on PAM signaling and miR-133a expression, offering promise for targeted therapies in disrupting oncogenic pathways in MCF-7 breast cancer cells. This insight could advance breast cancer treatment strategies.

Osteoarthritis (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. p<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 HLA-DQA1 downregulation and MAPK8IP3 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 HLA-DQA1 downregulation and MAPK8IP3 upregulation, could be novel molecular biomarkers to diagnose RA.