Iranian Journal of Biotechnology最新文献

Background: Functional dyspepsia (FD) is a common gastrointestinal disorder with multifactorial etiology involving impaired motility, mucosal barrier disruption, and inflammation. Non-pharmacological biotechnological interventions, such as external biomechanical modulation, have demonstrated therapeutic benefits; however, the underlying molecular mechanisms remain largely unexplored.

Objectives: To investigate the transcriptomic and molecular changes induced by external biomechanical modulation in a rat model of FD and explore its potential as a physical biotechnological intervention for gastrointestinal dysfunction.

Materials and methods: Thirty-six male Wistar rats were randomly assigned to control, FD model, and biomechanical modulation intervention groups. FD was induced using a multifactorial approach (tail clamping stimulation + irregular diet + ice-cold saline gavage), and external biomechanical modulation was administered daily for one week. Gastrointestinal motility was assessed by measuring gastric emptying and intestinal propulsion rates. Duodenal tissues were analyzed using transcriptome sequencing, differential gene expression profiling, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Serum levels of TNF-α, IFN-γ, and IL-1β, as well as expression of tight junction proteins Occludin and ZO-1, were assessed via ELISA, immunofluorescence, and Western blotting.

Results: FD rats exhibited reduced motility and villus atrophy, with elevated inflammatory cytokines and downregulated tight junction proteins. Transcriptomic profiling revealed significant gene expression changes in pathways related to digestion, nutrient absorption, immune modulation, and epithelial barrier integrity. KEGG analysis highlighted the involvement of PI3K-Akt signaling, neuroactive ligand-receptor interaction, and absorption-related pathways. PI3K-Akt pathway is an important pathway to regulate cell growth, proliferation and metabolism, and plays an important regulatory role in gastrointestinal motility disorders. External biomechanical modulation reversed these alterations, improving motility, reducing inflammation, and restoring mucosal integrity. Compared with the model group, the gastric emptying rate was significantly improved, and the small intestinal propulsion rate was increased by 9%.

Conclusion: This study demonstrates that external biomechanical modulation exerts relevant effects on gastrointestinal function in FD through transcriptomic regulation of immune and barrier-related pathways. Further research should explore clinical applications and detailed mechanistic insights.

Background: Epigenetic modifiers such as lysine acetyltransferase 2A (KAT2A) have been reported to be the key regulators of gene expression in various cancers, including colorectal cancer (CRC). The transcriptomic effect of KAT2A deficiency in CRC and its implication on cancer-related pathways remains poorly elucidated.

Objectives: The objective of this research was to investigate genome-wide transcriptional alterations induced by KAT2A knockout in colorectal cancer cells with an eye toward the recognition of putative molecular targets for diagnosis or therapy.

Materials and methods: KAT2A-knockout HCT116 cell high-throughput RNA sequencing data (GSE246881) were analyzed. Differentially expressed genes (DEGs) were defined by DESeq2. Functional enrichment analysis, including Gene Ontology (GO) and KEGG pathways, and protein-protein interaction (PPI) network building were performed using integrated bioinformatics tools.

Results: KAT2A knockout resulted in 626 DEGs, predominantly downregulated, and indicated a potential role of KAT2A as a transcriptional activator. Enrichment analyses revealed significant involvement of cancer-related pathways such as MAPK and mTOR. PPI network analysis revealed key hub genes such as AKT1, VEGFA, and PLEC that are involved in tumor growth and may be future biomarkers or therapeutic targets.

Conclusion: KAT2A plays a pivotal role in oncogenic signaling pathways in CRC. The identified genes and pathways here present promising prospects for biotechnological application in cancer biomarker identification and targeted therapy, demonstrating the potential of KAT2A-centered regulatory networks in guiding CRC management strategies.

Advancements in nucleic acid therapeutics have opened new avenues for treating genetic diseases, with antisense oligonucleotides (ASOs) such as antisense RNA (as RNA) emerging as promising candidates. RNA medicine, targeting various RNA molecules, offers potential therapeutic interventions. RNA-based therapeutics encounter challenges like stability, delivery, and off-target effects. Advances in delivery systems, such as lipid and polymeric nanoparticles and virus-like particles, offer solutions to enhance efficacy. This review explores the mechanisms and applications of RNA therapeutics, focusing on antisense oligonucleotides. Several platforms like lipid nanoparticles, polymeric nanoparticles, cell-penetrating peptides, exosomes, polyplexes, and virus-like particles (VLPs) for antisense RNA delivery are utilized to overcome challenges such as RNA stability and intracellular delivery. The potential of bacteriophages and VLPs as versatile delivery systems for RNA therapeutics targeting bacterial infections, biofilm eradication, cancer therapy, and viral infections is explored. Utilizing bacteriophages for targeted antisense RNA delivery improves therapeutic outcomes. Bacteriophage systems are advantageous due to ease of development, large cargo capacity, ability to carry non-DNA payloads, and relative safety, making them effective nanocarriers. The review also highlights FDA-approved ASO drugs and CRISPR-derived approaches for antibacterial and antiviral therapy. Through an in-depth analysis of platforms, mechanisms, and applications, this review provides insights into the expanding landscape of RNA therapeutics and their clinical implications.

Background: Characterizing tumor-associated gene expression variations in breast cancer is crucial for identifying molecular drivers and therapeutic targets, thereby advancing precision strategies for early detection, prognosis, and treatment optimization.

Objectives: This study aimed to investigate the oncogenic role of death-associated protein-like 1 (DAPL1) in breast cancer.

Materials and methods: We employed a bioinformatics approach to conduct a comprehensive analysis of DAPL1, including DNA methylation, genetic alterations, kinase analysis, immune cell infiltration, and signaling pathways. The breast cancer datasets from TCGA (the cancer genome atlas) and GEO (gene expression omnibus) were utilized.

Results: DAPL1 is lowly expressed in breast cancer tissues compared to normal tissues. In the TCGA-BRCA (breast invasive carcinoma) cohort, we observed a correlation between low expression of DAPL1 and poor clinical prognosis regarding overall survival. Based on the survival data of GEO, the low DAPL1 expression was associated with a poor prognosis of distant metastasis-free and relapse-free survival. Furthermore, DAPL1 expression was linked to the mutation status or copy number variation of several genes, such as MAP3K1 (mitogen-activated protein kinase kinase kinase 1), NUP98 (nucleoporin 98), and CCDC59 (coiled-coil domain containing 59). The infiltration level of immune cells (e.g., M1 macrophage, B cells, etc.) may be involved in the etiology of breast cancer. Based on the DAPL1-correlated genes, enrichment analysis data indicated the association between DAPL1 expression and a series of biological issues, such as ubiquitin proteasome pathway. Additionally, there were several potential DAPL1-associated phosphorylation kinases, including CDC2 (cell division cycle 2), MAPK (mitogen-activated protein kinases), and PKA (protein kinase A).

Conclusion: DAPL1 has been recognized as a prognostic biomarker in breast cancer. The molecular mechanisms may involve protein phosphorylation, immune cell infiltration, and several biological issues, especially protein ubiquitination.

Background: Lung cancer is one of the most prevalent cancers, with 80%-85% of cases being non-small cell lung cancer (NSCLC).

Objectives: This study investigated the effect of cardiac troponin I (cTnI) on NSCLC cells and its molecular mechanism.

Materials and methods: The overexpression and knockdown of cTnI were performed in NSCLC cells using lentivirus. Expression assays to analyse gene mRNA levels were performed using RT- PCR, and Western blot was used to detect the protein expression. Cell proliferation capacity was tested using MTT and colony formation assays, and a Transwell^® assay was used to detect cell migration and invasion. The in vivo experiments were performed using xenografts in nude mice.

Results: cTnI expression was increased in NSCLC tissue and cells. The overexpression of cTnI in NSCLC cells promoted their development, and the knockdown of cTnI inhibited the proliferation and migration of lung cancer cells. Additionally, cTnI promoted the expression of Notch and Kras proteins in lung cancer cells. The xenograft experiments in nude mice yielded the same results.

Conclusion: Cardiac troponin I affects the proliferation and migration of NSCLC cells by promoting the expression of Notch and Kras proteins, and the knockdown of cTnI significantly inhibits the growth and development of NSCLC cells.

Evidence acquisition: This narrative review included articles sourced from databases such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Scopus, without time limitations. Studies on c-miRNAs related to exercise were reviewed, and the search strategy involved using keywords such as "microRNA," "exercise," and "biomarkers." The selected studies were reviewed based on their relevance to exercise-related c-miRNAs and their contributions to the field.

Results: The review identifies multiple c-miRNAs that are sensitive to exercise-induced changes, with miR-1, miR-126, miR-21, and miR-146a showing significant correlations with cardiovascular and muscle adaptations. These findings suggest that c-miRNAs may serve as reliable indicators for individualized training programs, highlighting the importance of molecular responses in tailoring exercise regimens to optimize performance and health outcomes.

Conclusions: c-miRNAs offer promising potential for personalized exercise prescriptions. Future studies should aim to elucidate the full regulatory networks and assess the variability of these biomarkers across diverse populations and exercise modalities. Clinicians and sports practitioners can apply this knowledge to refine training strategies, improving athletic performance and health monitoring.

Background: The use of synthetic hormones for induced breeding of fish has been a long-standing trend. Studies have demonstrated that exogenous administration of synthetic androgens are effective to improve milt quality of male fish.

Objectives: This study aimed to evaluate the impact Testosterone propionate (TP), a synthetic androgen, on the quality of milt and the preservation (short duration) of Gilthead Seabream semen at 4 oC in oxygen and Fish Ringer's medium.

Materials and methods: Sexually matured male fishes were given intra muscular injection of Testosterone propionate (TP) at a dose of 1.0 mL. Kg^-1, and a control group was maintained without hormone injection. After 36 hours, milt was collected and evaluated for sperm motility, density, sperm viability and colour. Semen preserved at 4 oC in oxygen and Fish Ringer's medium was examined for sperm motility (%), motility duration (sec) and viability (%) at 24,48,72,96 and 120 hours.

Results: Significant change in colour or pH of the milt was not observed. Milt's consistency changed from being thick to waterier. The hormone injected fish group had an increased level of milt volume and sperm density than the control. Milt stored at 4 oC in oxygen atmosphere showed higher sperm cell quality than that stored in Fish Ringer's medium.

Conclusion: The results of this study can be used as a guideline for induced breeding and hatchery production of Gilthead Seabream, S.aurata.

Background: MiR-27a-3p was linked to the growth, progression, and metastasis of many cancers; however, its role in endometrial cancer (EC) and the related mechanisms has not received as much research. Leukemia inhibitory factor receptor (LIFR) has been considered a prognostic and immune biomarker for EC. This work sought to determine if miR-27a-3p regulates LIFR in the malignant development of EC cells and to investigate the signaling pathways involved.

Objectives: The purpose of this study was to investigate the function and mechanism of miR-27a-3p in the growth and EMT of EC.

Materials and methods: The TCGA database predicted the expression levels of miR-27a-3p and LIFR in the EC. The target Scan database, along with the dual luciferase experiment, confirmed the targeting link between miR-27a-3p and LIFR. The levels of miR-27a-3p and LIFR in normal human endometrial cells EEC and EC cells were identified using RT-qPCR and Western blot tests. After interfering with miR-27a-3p or LIFR level, EC cell proliferation, migration, and invasion capacities, as well as the expression levels of proteins involved in EMT and the p38/MAPK signaling pathways were examined to investigate the intrinsic mechanism of miR-27a-3p regulation of EC.

Results: In EC cells, miR-27a-3p and LIFR were dramatically increased and decreased, respectively. miR-27a-3p targeting inhibited LIFR, further interfering with the p38/MAPK signaling pathway. Knocking down miR-27a-3p or overexpressing LIFR were efficient in suppressing the malignant biological characteristics and EMT of EC cells. Adding a p38/MAPK signaling pathway inhibitor partially decreases the influence of miR-27a-3p or LIFR on EC cells.

Conclusion: MiR-27a-3p activates the p38/MAPK signaling pathway by targeting LIFR down-regulation, promoting malignant biological behavior and EC cell EMT. This pathway may give ideas for EC clinical treatment.

Background: tuberculosis (tb)-health problems caused by chronic obstructive pulmonary disease (copd), as one of the important problems facing global public health, highlight its far-reaching effects. The pi3k/akt signaling pathway is implicated in inflammatory responses and cellular survival, suggesting its potential role in tb-copd pathogenesis.

Objective: This study integrated computational and experimental biotechnology approaches to identify key molecular mechanisms linking tb and copd, with a focus on the pi3k/akt signaling pathway.

Materials and methods: By analyzing two publicly available gene expression datasets (gse42057, gse83456), weighted network gene coexpression analysis technology was applied to identify differently expressed genes and key coexpression modules to explore their potential biological relevance and functional associations in more depth. Functional enrichment analysis (go/kegg) was performed to assess pathway involvement. Experimentally, a mycobacterium tuberculosis-infected bronchial epithelial cell model (16hbe) was established, and the pi3k/akt inhibitor ly294002 was utilized to evaluate its effects on apoptosis, proliferation, and epithelial-mesenchymal transition (emt) markers.

Results: Weighted correlation network analysis (Wgcna) identified a key module significantly enriched in pi3k/akt signaling. Experimental validation demonstrated that ly294002 treatment significantly improved cell survival (p < 0.05), reduced apoptosis, and restored epithelial integrity. It was found that an increase in epithelial cadherin expression levels was accompanied by a decrease in neuronal cadherin expression levels. This dynamic change shows that the characteristics and patterns of cell adhesion can significantly adapt to certain physiological or pathological processes. Furthermore, ly294002 suppressed pi3k/akt mrna expression and phosphorylation (p < 0.05), confirming pathway inhibition.

Conclusion: This study provides a novel biotechnological perspective on the role of pi3k/akt signaling in tb-COPD, highlighting its potential as a therapeutic target. The integrative use of bioinformatics and experimental validation strengthens our understanding of molecular pathogenesis，opens the way to precision medicine strategies in the treatment of respiratory diseases.

Background: Lung cancer remains one of the most prevalent and lethal cancers globally, often diagnosed at advanced stages, which impedes effective treatment. Recent advancements have highlighted exosomes as valuable biomarkers for early detection, prognosis, and therapeutic interventions in lung cancer. Exosomes, which carry molecular information from tumor cells, reflect tumor development and metastasis, offering potential for precision medicine.

Objective: This study aimed to develop a prognostic prediction model for lung cancer therapy based on miRNA profiling in exosomes. By performing bioinformatics analyses, we identified miRNAs and target genes associated with lung cancer treatment and their potential relationship with patient survival outcomes.

Materials and methods: Using the GSE207715 dataset, we applied machine learning models and a Transformer-based deep learning approach to predict nivolumab treatment efficacy in lung cancer patients. Additionally, miRNA-target gene interactions were predicted via miRNA databases, followed by Gene Ontology and KEGG pathway enrichment analyses. A Cox proportional hazards regression model was used to assess the relationship between miRNA expression and patient survival.

Results: Significant differences were observed in the miRNA profiles of exosomes from patients with different nivolumab treatment outcomes, though the differences were relatively small. Machine learning models achieved prediction accuracies ranging from 0.6731 to 0.6923, while the deep learning model outperformed these methods with an accuracy of 0.9412. The hsa-let-7c miRNA showed statistical significance in multivariate survival risk analysis (p = 0.0152).

Conclusion: This study demonstrates the potential of miRNA profiling in exosomes for predicting treatment efficacy and survival in lung cancer patients. The deep learning model's ability to capture subtle miRNA expression differences provides a robust platform for personalized treatment strategies in non-small cell lung cancer.