Numerous studies have demonstrated the existence of stable regulatory RNAs, microRNAs (miRNAs), in the circulation and have shown that the spectrum of these extracellular miRNAs is affected by ...various pathologic conditions including cancers.
Circulating miRNAs have been the focus of numerous cancer biomarker discovery efforts over the past few years; however, a considerable number of these studies have yielded inconsistent and irreproducible findings. Here, we have summarized and compared the results of studies covering 8 different cancer types to address key questions, including the possibility of using circulating miRNA to detect cancers and what factors may affect miRNA signatures. Although identifying circulating miRNA signatures to detect specific types of early stage cancers can be challenging, study results suggest that it may be possible to use miRNAs to detect cancers in general.
Circulating miRNA is a rich source for potential disease biomarkers; however, factors, both intrinsic and extrinsic, that may affect measurement of circulating miRNA have not been fully characterized. Better understanding of intra- and intercellular miRNA trafficking and the fundamental biology of cancer cell-derived lipid vesicles may facilitate the development of circulating miRNA-based biomarkers for cancer detection and classification.
MicroRNAs (miRNAs) are short regulatory RNAs that modulate the transcriptome and proteome at the post‐transcriptional level. To obtain a better understanding on the role of miRNAs in the progression ...of cervical cancer, meta‐analysis and gene set enrichment analysis were used to analyze published cervical cancer miRNA studies. From 85 published reports, which include 3,922 cases and 2,099 noncancerous control tissue samples, 63 differentially expressed miRNAs (DEmiRNAs) were identified in different stages of cervical cancer development (CIN 1‐3 and CC). It was found that some of the dysregulated miRNAs were associated with specific stages of cervical cancer development. To illustrate the impact of miRNAs on the pathogenesis of cervical cancer, a miRNA‐mRNA interaction network on selected pathways was built by integrating viral oncoproteins, dysregulated miRNAs and their predicted/validated targets. The results indicated that the deregulated miRNAs at the different stages of cervical cancer were functionally involved in several key cancer related pathways, such as cell cycle, p53 and Wnt signaling pathways. These dysregulated miRNAs could play an important role in cervical cancer development. Some of the stage‐specific miRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cancer development.
Abstract
Background
The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic ...targets for DCM.
Methods
We downloaded four datasets from the Gene Expression Omnibus (GEO) database: GSE141910, GSE3585, GSE42955 and GSE79962. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed to identify gene panels related to DCM. Meanwhile, the CIBERSORT algorithm was used to estimate the immune cells in DCM tissues. Multiple machine learning approaches were used to screen the hub genes and immune cells. Finally, the diagnostic value of the hub genes was assessed by receiver operating characteristic (ROC) analysis. An experimental mouse model of dilated cardiomyopathy was used to validate the bioinformatics results.
Results
FRZB and EXT1 were identified as hub biomarkers, and the ROC curves suggested an excellent diagnostic ability of the above genes for DCM. In addition, naive B cells were upregulated in DCM tissues, while eosinophils, M2 macrophages, and memory CD4 T cells were downregulated in DCM tissues. The increase in two hub genes and naive B cells was validated in animal experiments.
Conclusion
These results indicated that FRZB and EXT1 could be used as promising biomarkers, and eosinophils, M2 macrophages, resting memory CD4 T cells and naive B cells may also affect the occurrence of DCM.
The association between systemic iron status and lung function was conflicting in observational studies. We aim to explore the potential causal relationships between iron status and the levels of ...lung function using the two-sample Mendelian randomization (MR) design.
Genetic instruments associated with iron status biomarkers were retrieved from the Genetics of Iron Status (GIS) consortium (
= 48,972). Summary statistics of these genetic instruments with lung function were extracted from a meta-analysis of UK Biobank and SpiroMeta consortium (
= 400,102). The main analyses were performed using the inverse-variance weighted method, and complemented by multiple sensitivity analyses.
Based on conservative genetic instruments, MR analyses showed that genetically predicted higher iron (beta: 0.036 per 1 SD increase, 95% confidence interval (CI): 0.016 to 0.056,
= 3.51 × 10
), log10-transformed ferritin (beta: 0.081, 95% CI: 0.047 to 0.116,
= 4.11 × 10
), and transferrin saturation (beta: 0.027, 95% CI: 0.015 to 0.038,
= 1.09 × 10
) were associated with increased forced expiratory volume in 1 s (FEV1), whereas higher transferrin was associated with decreased FEV1 (beta: -0.036, 95% CI: -0.064 to -0.008,
= 0.01). A significant positive association between iron status and forced vital capacity (FVC) was also observed. However, there is no causal association between iron status and FEV1-to-FVC ratio (
= 0.10). Similar results were obtained from the liberal instruments analyses and multiple sensitivity analyses.
Our study provided strong evidence to support that higher iron status is causally associated with higher levels of FEV1 and FVC, but has no impact on airway obstruction, confirming iron status as an important target for lung function management.
A biomimetic receptor for glucose has been developed with high affinity and selectivity. The receptor was efficiently synthesized in three steps through dynamic imine chemistry followed by ...imine‐to‐amide oxidation. The receptor features two parallel durene panels, forming a hydrophobic pocket for CH⋅⋅⋅π interactions, and two pyridinium residues directing four amide bonds towards the pocket. These pyridinium residues not only improve solubility but also provide polarized C−H bonds for hydrogen bonding. Experimental data and DFT calculations show that these polarized C−H bonds significantly enhance substrate binding. These findings demonstrate the power of dynamic covalent chemistry for creating molecular receptors and using polarized C−H bonds for boosted carbohydrate recognition in water, providing a foundation for developing glucose‐responsive materials and sensors.
Biomimetic receptor for glucose has been developed by using dynamic imine chemistry followed by imine‐to‐amide oxidation. The design of the receptor features two parallel durene panels forming a hydrophobic pocket. The incorporation of two pyridinium residues enhances water solubility and improves substrate binding by establishing more hydrogen bonds.
The burgeoning demand for lithium across various sectors, most notably in lithium-ion batteries, necessitates the development of efficient extraction and purification methodologies. As a response to ...this imperative, the design of synthetic receptors exhibiting high selectivity and affinity for lithium ions has emerged as a crucial area of research. This investigation proposes a simple and effective approach to high-performance lithium receptors that capitalizes on ion-dipole interactions as the principal driving force for lithium binding. Our investigation encompasses the design, synthesis, and evaluation of five distinct ionophores characterized by varied ion-dipole interactions with lithium, culminating in significantly enhanced binding affinity and Li
+
/Na
+
selectivity compared to conventional macrocyclic crown ether-based receptors. Moreover, we identify a new building block based on pyridine-
N
-oxide, which serves as an efficacious motif for developing receptors with augmented lithium-binding capacities. Additionally, our findings demonstrate a rapid and efficient solid-liquid extraction process for LiCl in the presence of a substantial excess of NaCl and KCl, employing the newly discovered ionophore. Collectively, this study contributes valuable insights into molecular design strategies for high-performance lithium receptors and advocates for continued exploration of sustainable molecular materials to enhance lithium recognition and extraction efficiencies.
Incorporating strong ion-dipole interactions within acyclic molecular frameworks can remarkably enhance both binding affinity and selectivity for lithium ion, offering a simple and effective strategy for developing high-performance lithium receptors.
Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumor growth and glutamine metabolism. However, the role of GLS1 in ...hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we reported that GLS1 expression was significantly increased in HCC tissues and correlated with serum AFP, tumor differentiation, lymphatic metastasis, TNM stage, and poorer patient outcome. We further showed that GLS1 promoted colony formation and cell proliferation of HCC cells. Furthermore, our data showed that GLS1 inhibitor compound 968 inhibited the proliferation of HCC cells in a dose-dependent manner. Importantly, we found that GLS1 overexpression increased p-AKT, p-GSK3β and cyclinD1 expression, and had no influence on total AKT and GSK3β protein level, indicating that GLS1 was involved in AKT/GSK3β/CyclinD1 pathway. It is suggested that GLS1 promotes proliferation in HCC cells probably via AKT/GSK3β/CyclinD1 pathway and may be a potential target for anti-hepatocellular carcinoma cancer.
•GLS1 expression is highly dysregulated in HCC tissues and associated with malignant clinical parameters.•GLS1 promotes colony formation and cell proliferation of HCC cells.•GLS1 inhibitor compound 968 inhibited the proliferation of HCC cells in a dose-dependent manner.•GLS1 was involved in AKT/GSK3β/CyclinD1 pathway in HCC cells.
Background. Antioxidants attracted long-standing attention as promising preventive agents worldwide. Previous observational studies have reported that circulating antioxidants are associated with ...reduced mortality; however, randomized clinical trials indicate neutral or harmful impacts. The association of long-term circulating antioxidant exposure with longevity is still unclear. Objectives. We aim to determine whether long-term circulating antioxidant exposure is causally associated with longevity in the general population using the two-sample Mendelian randomization (MR) design. Methods. Genetic instruments for circulating antioxidants (ascorbate, lycopene, selenium, beta-carotene, and retinol) and antioxidant metabolites (ascorbate, alpha-tocopherol, gamma-tocopherol, and retinol) were identified from the largest up-to-date genome-wide association studies (GWASs). Summary statistics of these instruments with individual survival to the 90th vs. 60th percentile age (11,262 cases and 25,483 controls) and parental lifespan (N=1,012,240 individuals) were extracted. The causal effect was estimated using the inverse-variance weighted method in the main analysis and complemented by multiple sensitivity analyses to test the robustness of results. Results. We found that genetically determined higher concentration of circulating retinol (vitamin A) metabolite was casually associated with a higher odds of longevity (OR, 1.07; 95% CI, 1.02–1.13; P<0.01) and increased parental lifespan (lifespan years per 10-fold increase: 0.17; 95% CI, 0.07–0.27; P<0.01). Present evidence did not support a causal impact of circulating ascorbate (vitamin C), tocopherol (vitamin E), lycopene, selenium or beta-carotene on life expectancy. No evidence was identified to show the pleiotropic effects had biased the results. Conclusions. Long-term higher exposure to retinol metabolite is causally associated with longevity in the general population. Future MR analyses could assess the current findings further by utilizing additional genetic variants and greater samples from large-scale GWASs.
Natural hydrate-bearing sediments attract broad attention due to their important role in natural gas extraction and climate change. Their mechanical behavior, governed by hydrate saturation and ...spatial distribution (i.e. pore habits), requires in-depth understanding. The discrete element method (DEM) serves as an important tool to reveal the micromechanics of particle-hydrate interactions and the macroscopic behavior of hydrate-bearing sediments. However, a comprehensively validated DEM modeling of hydrate-bearing sediments is missing in previous studies. This study introduces a generic DEM-based modeling framework for hydrate-bearing sands, integrating modeling and parameter calibrations for various pore habits. The framework's efficacy is demonstrated through calibration against triaxial tests of hydrate, sand, and hydrate-bearing sands, yielding close agreement between the experimental observations and simulation results. Utilizing this modeling framework, the impact of pore habits on the mechanical behavior of hydrate-bearing sands is investigated. Results show that the strength and stiffness of hydrate-bearing sands are significantly enhanced by the presence of hydrate, and this enhancement is modulated by hydrate pore habits. In addition, compared with pure sand, hydrate-bearing sand exhibits a narrower shear band, a lower particle rotation angle, and a more brittle failure pattern. The findings advocate for considering hydrate pore habits to accurately predict sediment behavior.
The importance of cell pyroptosis in immunity regulation is becoming increasingly obvious, especially in diseases of the cardiovascular system. Nevertheless, it is unknown whether the pyroptosis ...signalling pathway is involved in the immune microenvironment regulation of dilated cardiomyopathy (DCM). Therefore, the purpose of the study was to investigate the influence of pyroptosis on the immune environment in dilated cardiomyopathy. We found that expression of 19 pyrolysis-related genes (PRGs) in DCM samples was altered compared to healthy samples. Subsequently, based on these 12 hub pyrolysis-related genes, we developed a classifier that can distinguish between healthy samples and DCM samples. Among the hub pyrolysis-related genes, RT–PCR analyses demonstrated that five of them exhibited significant differential expression in DCM. Interestingly, we observed that immune characteristics are correlated with pyroptosis: higher expression of GSDMD is positively correlated with infiltrating activated pDCs; GSDMD is negatively correlated with Tregs; CASP1 is positively related to parainflammation; and CASP9 is negatively related to the type II IFN response. In addition, distinct pyroptosis-mediated patterns were identified, and immune characteristics under distinct patterns were revealed: pattern B mediates an active immune response, and pattern A leads to a relatively mild immune response to DCM. We also compared the biological functions between these patterns. Compared with pattern A, pattern B had more abundant pathways, such as the NOTCH signalling pathway and pentose phosphate pathway. In summary, this study proves the important influence of pyrolysis on the immune microenvironment of dilated cardiomyopathy and provides new clues for understanding the pathogenesis of dilated cardiomyopathy.
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