Molecular Biotechnology最新文献

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p.

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related deaths worldwide, and there is an urgent need to develop personalized prognostic models for effective treatment strategies. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways has been confirmed to engage in multiple cancer progression, prognosis, and immunotherapy benefits. However, the prognostic significance and immunotherapy response of cGAS-STING pathway-associated genes (CSPAGs) in LUAD remain unclear. Herein, we aimed to establish a CSPAG-based prognostic signature for LUAD patients. A total of 139 CSPAGs derived from the GSEA website were enrolled for subsequent analysis. Univariate Cox regression analysis shows that 22 of 139 CSPAGs were associated with LUAD prognosis. Lasso analysis identified 6 CSPAGs (IFNE, NFKB2, POL3RG, TRAF2, TICAM1 and NLRC3) as the most significant prognostic CSPAGs with the best model efficacy. The CSPAG signature classified LUAD patients into low-risk (LR) and high-risk (HR) groups. Kaplan-Meier analysis demonstrated that patients in the LR group had significantly better overall survival (OS) than those in the HR group (p < 0.05 represents statistical significance), indicating the predictive power of the CSPAG signature in LUAD prognosis. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) values for the CSPAG signature were higher than those for other well-established predictive factors, suggesting that the CSPAG signature had a higher predictive efficacy. The CSPAG nomogram incorporating clinical factors such as age, TNM status and the CSPAG risk score accurately predicted the OS of LUAD patients at 1, 3, and 5 years, indicating its potential clinical application in LUAD prognosis. Furthermore, we investigated the expression pattern of the 6 signature CSPAGs in different LUAD subpopulations with distinct clinical features. The CSPAG risk score was increased in the immune-high groups, suggesting a positive correlation between immune infiltration degree and CSPAG risk score. There was a heterogenicity of somatic mutation landscape between the two groups. The LR group had a strong immune cell activity, and most immune checkpoints were significantly expressed in the LR group, implying that this group benefited from immune checkpoint blockade (ICB) therapy. In addition, we verified the high predictive accuracy of the CSPAG signature in the GSE31210 and GSE203360 datasets. Taken together, this study established a CSPAG-based prognostic signature for LUAD patients with high predictive efficacy and clinical relevance. The association between CSPAGs and immune infiltration, and ICB therapy response, highlights the potential of the CSPAG signature as a personalized treatment strategy for LUAD patients.

Recently biocementation has got attention of many researchers worldwide as one of the most potent techniques for sustainable construction. Several studies have been carried out worldwide on biocementation by urea hydrolysis. Biocementation by bacterially induced calcium carbonate precipitation by different bacterial species has been among the most widely researched areas in this field. Biocementation has proved efficient in enhancing the strength and durability of cement-based materials. However, no significant work has been carried out to determine the performance of biocemented specimens at elevated temperatures. This study primarily focuses on the effects of high temperatures (300, 450, and 600 °C) on the compressive strength of two types of biocemented specimens prepared by using ureolytic bacteria and rich in urease watermelon seeds. The motive behind testing these two types is to know how the enzyme induced or microbially induced react to temperature elevation. Also, the effect of different cooling techniques (viz., natural cooling, water spray cooling and fire extinguishing foam spray cooling) were studied. These cooling techniques were selected so as to check which cooling technique should be preferred in case of fire situation in a cement-based structure. Results show that biocemented specimens can perform very good up to the temperature 300 °C as compared to control specimens in terms of compressive strength. At 450 °C temperature, there is no significant difference in compressive strengths of control and biocemented specimens. When the specimens were subjected to 600 °C, biocemented specimens showed lower strength than control specimens at the same temperature due to denser microstructures. Thus, biocemented cement mortar should not be used in reactors, muffles and ovens where temperature would go above 450 °C.

The field of gene therapy has witnessed significant advancements in the utilization of Adeno-associated virus (AAV) owing to its inherent biological advantages. Targeted AAV vectors are generated through genetic or chemical modification of the capsid for user-directed purposes. However, this process can result in imbalances in viral protein sequence homogeneity, stoichiometry, and functional transduction vector units, thereby introducing new challenges. This mini review focuses on the ongoing efforts to develop targeted vectors, which inadvertently present unsolicited obstacles for clinical application and provided perspectives on future directions.

Perinatal white matter injury (WMI), which is prevalent in premature infants, involves M2 microglia affecting oligodendrocyte precursor cells (OPCs) through exosomes, promoting OPC growth and reducing WMI. The molecular mechanism of WMI remains unclear, and this study explored the role of M2 microglia-derived exosomes in WMI. A tMCAO rat model was constructed to simulate WMI characteristics in vivo. Cresyl violet staining, neurobehavioral tests, rotarod tests, immunofluorescence and immunochemistry were used to assess the role of exos-derived miR-144-5p in pathological and neurological changes in rats. OGD/R cellular models were constructed to mimic WMI characteristics in vitro. CCK-8, TUNEL, Western blotting and immunofluorescence were used to assess the role of exos-derived miR-144-5p in OPC phenotypes. Rescue assays were used to assess the role of the PTEN/AKT pathway in miR-144-5p-mediated OPC phenotypes. Bioinformatics and mechanistic experiments were used to assess the association of PTEN or KLF12 with miR-144-5p in OPCs. M2-Exos suppressed cerebral injury and facilitated demyelination repair in rats post WMI. M2-Exos suppressed OGD/R-stimulated OPC apoptosis and facilitated OGD/R-stimulated OPC differentiation. M2-Exo-derived miR-144-5p suppressed OGD/R-stimulated OPC apoptosis and facilitated OGD/R-stimulated OPC differentiation. M2-Exo-derived miR-144-5p suppressed cerebral injury and facilitated demyelination repair in rats post WMI. MiR-144-5p suppressed OGD/R-stimulated OPC apoptosis and facilitated OGD/R-stimulated OPC differentiation through PTEN downregulation. MiR-144-5p targeted the KLF12 3'UTR to repress PTEN transcription in OPCs. M2 microglia secrete miR-144-5p to reduce WMI by targeting KLF12 in OPCs, inhibiting PTEN/AKT pathway activity, and offering potential targeted therapeutic insights for WMI.

Quantitative polymerase chain reaction (qPCR) is a vital molecular technique for biomarker detection; however, its clinical application is impeded by the scarcity of robust biomarkers and the inherent limitations of the technology. This study conducted a bibliometric analysis of 4063 qPCR-based biomarker studies sourced from the Web of Science (WOS) database, employing VOSviewer and CiteSpace to generate multi-dimensional structural insights into this field. The results reveal a growing trend in research within this domain, with gene expression analysis playing a central role in the identification of potential biomarkers. Among these, cancer-related biomarkers are the most prominent, while research on biomarkers for other diseases remains limited. Liquid biopsy biomarkers, including microRNA (miRNA), circulating free DNA (cfDNA), and circulating tumor DNA (ctDNA), are increasingly being explored. The integration of bioinformatics, omics analysis, and high-throughput technologies with qPCR is accelerating biomarker discovery. Furthermore, large-scale parallel sequencing is emerging as a potential alternative to relative quantification and microarray techniques. Nevertheless, qPCR remains essential for validating specific biomarkers, and further standardization of its protocols is necessary to enhance reliability. This study provides a systematic analysis of qPCR-based biomarker research and underscores the need for future technological integration and standardization to facilitate broader clinical applications.

Opioids are the primary regimens for perioperative analgesia with controversial effects on oncological survival. The underlying mechanism remains unexplored. This study developed survival-related gene co-expression networks based on RNA-seq and clinical characteristics from TCGA cohort. Two survival-related networks were identified, and drug-induced transcriptional profiles were predicted. Immune cell infiltration algorithm, least absolute shrinkage and selection operator (LASSO) regression, and cox proportional models were executed to explore the correlation between opioid-related drugs and prostate cancer patient prognosis. The opioid receptor agonists, represented by tramadol, were evidenced for anti-survival effects on prostate cancer by facilitating the DNA replication and cell cycle, and immune cell infiltration. Conversely, opioid receptor antagonists showed pro-survival effects. A novel prognostic model containing CNIH2, MCCC1, and Gleason scores was established and validated in two independent cohorts. This study revealed opioids' effect on prostate cancer progression, and provided a novel model to predict these regulations in clinical outcomes.

To deeply investigate the mechanism of ferroptosis-related genes in the process of bone nonunion based on the GEO database. And using Mendelian randomization to explore the causal association of 15 trace elements with the occurrence of bone nonunion. Bone nonunion RNA-seq data were retrieved and downloaded from the GEO database. The differentially expressed genes in bone nonunion were identified using two differential expression analysis methods, "limma" and "WGCNA". Random Forest Tree, Support Vector Machine, and Lasso-cox were used to analyze and screen the genes related to ferroptosis in bone nonunion; A risk model of bone nonunion was constructed based on the screened ferroptosis-related genes; based on this, the pathway mechanism of ferroptosis-related genes involved in the occurrence and development of bone nonunion was further investigated. Mendelian randomization analysis was performed using inverse variance weighting as the main analysis method, and weighted median, Weighted mode, Mr-Egger, and Simple mode were used as complementary methods. Heterogeneity was detected using Cochran's Q test and funnel plot analysis, horizontal pleiotropy was detected using Mr-Egger intercept, and sensitivity analyses were performed using the "leave-one-out" method. PTGS2/PRKCA/MAPK14 all showed excellent diagnostic efficacy for bone nonunion. The risk prediction model based on PTGS2, PRKCA, and MAPK14 showed good predictive efficacy and clinical benefit rate for bone nonunion. Ferroptosis core gene PRKCA may be involved in the VEGF signaling pathway to affect the cell cycle and inhibit fracture healing. MR analysis suggests that Potassium and Vitamin E are protective factors for the development of bone nonunion. Ferroptosis genes PTGS2/PRKCA/MAPK14 are potential diagnostic targets for bone nonunion. The down-regulation of PRKCA expression may inhibit fracture healing through the VEGF signaling pathway during the growth of blood vessels at fracture breaks. The results of MR suggested that Potassium and Vitamin E have a promoting effect on fracture healing.

Nucleolin (NCL) is a prevalent and widely distributed nucleolar protein in cells. While primarily located in the nucleolus, NCL is also found within the nucleoplasm, cytoplasm, and even on the cell surface. NCL's unique nature arises from its multifaceted roles and extensive interactions with various proteins. The structural stability of NCL is reliant on protease inhibitors, particularly in proliferating cells, indicating its essential role in cellular maintenance. This review is centered on elucidating the structure of NCL, its significance in host-viral interactions, and its various contributions to viral progeny production. This work is to enhance the scientific community's understanding of NCL functionality and its implications for viral infection processes. NCL is highlighted as a crucial host protein that viruses frequently target, exploiting it to support their own life cycles and establish infections. Understanding these interactions is key to identifying NCL's role in viral pathogenesis and its potential as a therapeutic target. Our current knowledge, alongside extensive scientific literature, underscores the critical role of host proteins like NCL in both viral infections and other diseases. As a target for viral exploitation, NCL supports viral replication and survival, making it a promising candidate for therapeutic intervention. By delving deeper into the intricacies of NCL-viral protein interactions, researchers may uncover effective antiviral mechanisms. This review aspires to inspire further research into NCL's role in viral infections and promote advancements in antiviral therapeutic development.

One kind of hydroxycinnamic acid is calceolarioside A. Plantago coronopus, Cassinopsis madagascariensis, and other organisms for whom data are available are known to have this naturally occurring compound. IC50 values of Calceolarioside A for ovarian cell lines (NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, UWB1.289) were 24.42, 13.50, 9.31, 14.90, 20.07, and 16.18 µM, respectively. IC50 values were 19.83 and 73.48 µM for tyrosinase and HMG-CoA reductase enzymes. The chemical activities of Calceolarioside A against HMG-CoA reductase and tyrosinase were assessed by conducting the molecular docking study, MM/GBSA calculation, and molecular dynamics (MD) simulation. The anticancer activities of this compound were evaluated against some ovarian cancer cells, such as NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, and UWB1.289 cell lines. The chemical activities of Calceolarioside A against some of the expressed surface receptor proteins (folate receptor, CD44, EGFR, Formyl Peptide Receptor-Like 1, M2 muscarinic receptor, and estrogen receptors) were investigated using computational methods. The results exhibited the interplay among atoms. The compound formed robust associations with both the enzymes and receptors. Calceolarioside A can hinder the functioning of these enzymes and the proliferation of malignant cells.