Molecular Biotechnology最新文献

To explore the relationship between BigET-1 and cardiac remodeling in hypertrophic obstructive cardiomyopathy (HOCM). A retrospective analysis was conducted on the data of 150 HOCM patients in a hospital from September 2021 to August 2023. According to the 2015 American Ultrasound Society's recommended standards for quantifying adult UGG cardiac lumen, left atrial enlargement is defined as having a left atrial diameter greater than 40 mm in males and greater than 38 mm in females. 150 HOCM patients were divided into a left atrial normal group (n = 97) and a left atrial enlargement group (n = 53). Comprehensive patient data were collected, including BigET-1in plasma, N-Terminalpro-B-TypeNatriureticPeptide (NT-pro-BNP), and High-sensitive C-reactive protein (Hs-CRP), as well as cardiac magnetic resonance imaging (CMR) imaging data. The relationship between BigET-1 levels and cardiac remodeling was analyzed. The two groups had no statistical difference in gender, age, heart rate, dyspnea, angina pectoris, etc. (P > 0.05). The χ²-test showed that patients in the left atrial enlargement group had an increased proportion of atrial fibrillation compared to those in the left atrial normal group (P < 0.05). Non parametric tests showed that the Big ET-1 and NT-pro-BNP in the left atrial enlargement group were significantly higher than those in the left atrial normal group (P < 0.05). The t-test results showed that there were statistical differences in Hs-CRP, left atrial anteroposterior diameter, interventricular septum thickness, and LVEDV between the left atrial enlargement group and the left atrial normal group (P < 0.05). Pearson correlation analysis showed that Big ET-1 was positively correlated withNT-pro-BNP, Hs-CRP, left atrial anteroposterior diameter, and interventricular septum thickness (P < 0.05). The multiple linear regression analysis showed that Big ET-1 was positively correlated with NT-pro-BNP and LADap (P < 0.05). In HOCM patients with atrial enlargement, the Big ET-1 is significantly elevated. Cardiac remodeling is more pronounced, indicating that Big ET-1 plays a role in cardiac remodeling in HOCM patients.

The promotive effect of P53 apoptosis effector related to PMP-22 (PERP) on lung adenocarcinoma (LUAD) has been confirmed. However, the N6-methyladenosine (m6A) modification of PERP to regulate LUAD progression have not been revealed. Bioinformatic analysis predicted the mechanism of PERP interacting with RBM15 and p53 pathway using GEPIA and The Cancer Genome Atlas (TCGA) databases. The qRT-PCR, cell function experiments, and western blotting were applied to further confirm the function and mechanism of PERP and RBM15 in LUAD cells. Methylated RNA immunoprecipitation (MeRIP) and mRNA stability assays were used to reveal the interaction between PERP and RBM15 in LUAD cells. PERP with high expression in LUAD showed the poor survival. Silencing PERP prevented LUAD cells to proliferate, migrate, and invade via activating p53 pathway, whereas overexpressing PERP showed the opposite effect on LUAD cells. Mechanistically, RBM15 overexpression could promote PERP m6A modification to enhance the PERP mRNA stability. In addition, RBM15 overexpression leading to LUAD cell malignancy was reversed by PERP knockdown. This study reveals that the m⁶A modification of PERP regulated by RBM15 enhances the tumorigenesis of LUAD by inhibiting the p53 signaling pathway, which may provide novel insights into the LUAD mechanism.

Autophagy regulates intermittent hypoxia (IH)-induced obstructive sleep apnea-hypopnea syndrome (OSAHS). We investigated the effects of IH and its withdrawal on cognitive function, autophagy, and lysophagy in OSAHS. An OSAHS rat model was established, and rats were divided into five groups: normoxia control, IH-4w (4-week IH), IH-6w (6-week IH), IH-8w (8-week IH), and IH-8w + 4w (8-week IH and 4-week normoxia). The cognitive behavior; mitochondrial and lysosomal morphology of the hippocampal tissue; mitochondrial respiratory function, permeability, and membrane potential; lysosomal function; autophagy- and lysophagy-related protein levels; and hypoxia-associated autophagy gene expression in rats were assessed. The cognitive function of rats in the IH-4w, IH-6w, and IH-8w groups was significantly impaired. In IH-8w cells, mitochondrial function was damaged with swollen morphology and decreased quantity, respiration, permeability, and membrane potential, along with significantly increased mitophagy-related protein ATG5 and LC3II/LC3 levels and decreased p62 levels. Expression of hypoxia-associated autophagy genes Becn1, Hif1, Bnip3, Bnip3l, and Fundc1 was significantly higher in the IH-8w group. Significantly increased LAMP2, CTSB, and ACP2 levels in IH-8w cells further indicated impaired lysosomal function. Lysophagy-related protein LAMP1, LC3II/LC3I, and TFEB levels were significantly increased in the IH-8w group, whereas p62 level was significantly decreased. The above listed evidence indicated damage to the mitochondria and lysosomes, as well as stimulation of mitophagy and lysophagy in IH-treatment OSAHS rat model. After withdrawing IH and culturing for 4 weeks in normal conditions, the cognitive function of rats improved, and mitophagy and lysophagy decreased. Our findings indicate that IH impairs cognitive function and promotes mitophagy and lysophagy in an OSAHS rat model, and IH withdrawal recovered the above effects.

To discover the molecular mechanism of Astragaloside IV (AS IV) in PM2.5-induced lung injury and pulmonary fibrosis (PF). A lung injury rat model was induced by PM2.5 and injected intraperitoneally with AS IV. Lungs were harvested to evaluate lung tissue injury and apoptosis. Rat alveolar epithelial cells L2 were exposed to PM2.5 and treated with AS IV. After cellular transfection, cell proliferation, LDH production, and apoptosis were measured. In both models, inflammatory factors and fibrotic indices were measured by ELISA and Western blot. miR-362-3p and RUNX1 interplay was explored and confirmed. Administration of AS IV attenuated PM2.5-induced lung tissue injury, inflammation, apoptosis, and PF in rats. AS IV enhanced proliferation and reduced LDH release, apoptosis, inflammation, and PF in PM2.5-treated L2 cells. MiR-362-3p upregulation improved PM2.5-induced L2 cell injury. AS IV improved PM2.5-induced lung injury by upregulating miR-362-3p. miR-362-3p had an inhibition effect on RUNX1 expression. RUNX1 upregulation weakened the therapeutic effect of AS IV on PM2.5-induced alveolar epithelial cell injury. AS IV inhibits lung injury and PF induced by PM2.5 by targeting RUNX1 through upregulation of miR-362-3p.

The study aimed to explore the potential of QiangJin mixture (QJM), a Chinese herbal compound prescription, in regulating MC3T3-E1 cell differentiation and to analyze the ingredients and therapeutic targets of QJM against osteoporosis based on network pharmacology. MC3T3-E1 cells were incubated with different concentrations of QJM-contained rat serum (5, 10, or 20%). After 14 days of cell culture, Alizarin Red staining was performed to assess the mineralization ability of osteoblasts. RT-qPCR was used to measure mRNA levels of osteogenesis-related genes. Western blot was conducted to measure protein levels of factors related to the BMP2/Smads pathway. Functional and pathway enrichment of overlapping targets for QJM and osteoporosis were analyzed using gene ontology and KEGG analyses. As shown by experimental results, QJM-contained serum led to calcium deposition, increased expression levels of osteogenesis-related genes, and activated BMP2/Smad/Runx2 signaling in MC3T3-E1 cells. A total of 125 active compounds and 162 disease-related targets were identified. The core targets were MAPK8, TP53, ESR1, STAT3, MAPK3, IL6, NFKB1, JUN, MAPK1 and AKT1. In conclusion, QJM promotes the osteogenic differentiation of MC3T3-E1 cells by activating the BMP2/Smads signaling. Additionally, QJM is an anti-osteoporotic mixture by regulating diverse therapeutic targets and signaling pathways.

Microbial infections pose a substantial global health challenge, particularly impacting immunocompromised individuals and exacerbating the issue of antimicrobial resistance (AMR). High virulence of pathogens can lead to severe infections and prolonged antimicrobial treatment, increasing the risk of developing resistant strains. Integrating machine-learning (ML) with DNA sequencing technologies offers potential solutions by enhancing microbial identification, virulence assessment, and antimicrobial susceptibility evaluation. This review explores recent advancements in these integrated approaches, addressing current limitations and identifying gaps in the literature. A comprehensive literature search was conducted across databases including PubMed, Scopus, Web of Science, and IEEE Xplore, covering publications from January 2014 to June 2024. Using a detailed Boolean search string, relevant studies focusing on ML applications in microorganism identification, antimicrobial susceptibility testing, and microbial virulence were included. The screening process involved a two-stage review of titles, abstracts, and full texts, with data extraction and critical appraisal performed using the QIAO tool. Data were analyzed through narrative synthesis to identify common themes and innovations. Out of 1,650 initially identified records, 19 studies met the inclusion criteria. These studies primarily focused on AMR, with additional research on microbial virulence and identification. Machine learning algorithms such as Random Forest, Support Vector Machines, and Convolutional Neural Networks, combined with DNA sequencing techniques like Whole Genome Sequencing and Metagenomic Sequencing, demonstrated significant advancements in predictive accuracy and efficiency. High-quality studies achieved impressive performance metrics, including F1-scores up to 0.88 and AUC scores up to 0.96. The integration of ML and DNA sequencing technologies has significantly enhanced microbial analysis, improving the identification of pathogens, assessment of virulence, and evaluation of antimicrobial susceptibility. Despite advancements, challenges such as data quality, high costs, and model interpretability persist. This review highlights the need for continued innovation and provides recommendations for future research to address these limitations and improve disease management and public health strategies. The systematic review is registered with PROSPERO (CRD42024571347).

Plant plastome are well studied due to their essential roles in photosynthesis and plant development. Comparative studies among plastome of closely related genera or families are limited, hindering our understanding of evolutionary changes and adaptation. This study presents a comparative analysis of 23 Caryophyllaceae plastome revealing a dynamic interplay of conserved and variable features. The genome size exhibited a moderate coefficient of variation (CV) of 2.58%. The large single-copy (LSC) and small single-copy (SSC) regions were highly conserved, with CVs of 2.55% and 2.00%, respectively. In contrast, the inverted repeat (IR) regions displayed greater variability, with a CV of 4.23%, indicating dynamic evolutionary processes. Exon counts varied significantly (CV 17.20%), while intron counts showed some variability (CV 7.79%), reflecting diverse gene structures. Coding sequences had moderate variability (CV 3.67%), while non-coding sequences varied more (CV 5.05%). tRNA counts were slightly variable (CV 2.67%), and GC content was notably consistent (CV 0.40%). This study includes the newly sequenced plastome of Drymaria villosa (GenBank accession OR790517), confirming its placement within Caryophyllaceae with significant diversification through phylogenetic analysis. Correlations (> 0.6) among plastome components and genome size reflect their tight evolutionary linkage, enhancing our understanding of plastome evolution in Caryophyllaceae and aiding future investigations into the ecological and medicinal potential of D. villosa and related species.