Tumor metastasis is a hallmark of cancer. The communication between cancer-derived exosomes and stroma plays an irreplaceable role in facilitating pre-metastatic niche formation and cancer ...metastasis. However, the mechanisms underlying exosome-mediated pre-metastatic niche formation during colorectal cancer (CRC) liver metastasis remain incompletely understood. Here we identified HSPC111 was the leading upregulated gene in hepatic stellate cells (HSCs) incubated with CRC cell-derived exosomes. In xenograft mouse model, CRC cell-derived exosomal HSPC111 facilitated pre-metastatic niche formation and CRC liver metastases (CRLM). Consistently, CRC patients with liver metastasis had higher level of HSPC111 in serum exosomes, primary tumors and cancer-associated fibroblasts (CAFs) in liver metastasis than those without. Mechanistically, HSPC111 altered lipid metabolism of CAFs by phosphorylating ATP-citrate lyase (ACLY), which upregulated the level of acetyl-CoA. The accumulation of acetyl-CoA further promoted CXCL5 expression and secretion by increasing H3K27 acetylation in CAFs. Moreover, CXCL5-CXCR2 axis reinforced exosomal HSPC111 excretion from CRC cells and promoted liver metastasis. These results uncovered that CRC cell-derived exosomal HSPC111 promotes pre-metastatic niche formation and CRLM via reprogramming lipid metabolism in CAFs, and implicate HSPC111 may be a potential therapeutic target for preventing CRLM.
Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in ...intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
Aluminum oxynitride (AlON) ceramics doped with different sintering aids were synthesized by spark plasma sintering process. The microstructures, mechanical, and optical properties of the ceramics ...were investigated. The results indicate that the optimal amount of sintering aids is 0.06 wt% La2O3 + 0.16 wt% Y2O3 + 0.30 wt% MgO. The addition of La3+ and Mg2+ decreases the rate of grain boundary migration in ceramics, promotes pore elimination, and inhibits grain growth. The addition of Y3+ facilitates liquid‐phase sintering of AlON ceramics. Moreover, the addition of Mg2+ effectively promotes twin formation in the ceramics, which hinders crack propagation and dislocation motion when the ceramics are loaded. Hence, the AlON ceramic doped with 0.06 wt% La2O3 + 0.16 wt% Y2O3 + 0.30 wt% MgO exhibits a relative density of 99.95%, an average grain size of 9.42 μm, and a twin boundary content of 10.3%, which contributes to its excellent mechanical and optical properties.
Abstract Background Previous studies concerning the association between maternal anxiety during pregnancy and adverse birth outcomes have provided controversial findings. Methods In this systematic ...review, a meta-analysis was utilized to investigate the association between maternal anxiety and preterm birth (PTB) and/or low birth weight (LBW). Literature was searched until June 2013. Only prospective cohort studies that reported data on maternal anxiety during pregnancy with PTB and/or LBW were included. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using fixed or random effects models depending on the size of heterogeneity. Results Twelve studies totaling 17,304 pregnant women reported PTB data; and six studies totaling 4948 pregnant women reported LBW data. Maternal anxiety during pregnancy was associated with significant increased risk of PTB (pooled RR=1.50, 95% CI=1.33–1.70) and LBW (pooled RR=1.76, 95% CI=1.32–2.33). Limitations Potential moderators could not be adequately considered due to insufficient information. In addition, the effects of different types of anxiety disorder on the risk of these adverse birth outcomes could not be investigated. Conclusions The results suggested that maternal anxiety during pregnancy was positively related to an increased risk of PTB and LBW. Healthcare providers should give close attention to anxiety in pregnant women and provide appropriate mental health support in order to improve outcomes for both mothers and infants.
The propensity of the activated neutrophils to form extracellular traps (NETs) is demonstrated in multiple inflammatory conditions. In this study, we investigated the roles of NETs in metastasis of ...hepatocellular carcinoma (HCC) and further explored the underlying mechanism of how NETs affect metastasis as well as the therapeutic value.
The neutrophils were isolated from the blood of human HCC patients and used to evaluate the formation of NETs. The expression of NET markers was detected in tumor specimens. A LPS-induced NET model was used to investigate the role of NETs on HCC metastasis. RNA-seq was performed to identify the key molecular event triggered by NETs, and their underlying mechanism and therapeutic significance were explored using both in vitro and in vivo assays.
NET formation was enhanced in neutrophils derived from HCC patients, especially those with metastatic HCCs. NETs trapped HCC cells and subsequently induced cell-death resistance and enhanced invasiveness to trigger their metastatic potential, which was mediated by internalization of NETs into trapped HCC cells and activation of Toll-like receptors TLR4/9-COX2 signaling. Inhibition of TLR4/9-COX2 signaling abrogated the NET-aroused metastatic potential. A combination of DNase 1 directly wrecking NETs with anti-inflammation drugs aspirin/hydroxychloroquine effectively reduced HCC metastasis in mice model.
NETs trigger tumorous inflammatory response and fuel HCC metastasis. Targeting NETs rather than neutrophils themselves can be a practice strategy against HCC metastasis.
Context:
Vitamin D deficiency is common in pregnant women. Nevertheless, the association between maternal vitamin D status during pregnancy and the risk of having small for gestational age (SGA) and ...low birth weight (LBW) infants is uncertain.
Objective:
The objective of this study was to investigate whether there is a correlation between maternal vitamin D deficiency during pregnancy and the risk of having SGA and LBW infants in a Chinese population.
Design and Participants:
This was a population-based birth cohort study that recruited 3658 eligible mother-and-singleton-offspring pairs.
Main Outcome Measures:
Serum 25-hydroxyvitamin D was measured by RIA. The rate and relative risk (RR) for SGA and LBW infants were calculated among subjects with vitamin D deficiency and insufficiency during pregnancy.
Results:
There was a positive correlation between maternal serum 25-hydroxyvitamin D level and offspring birth weight (r = 0.477; P < .001). Further analysis showed that 4.98% of neonates were LBW infants among the subjects with vitamin D deficiency (RR, 12.00; 95% confidence interval CI, 4.37, 33.00) and 1.32% among the subjects with vitamin D insufficiency (RR, 3.18; 95% CI, 1.07, 9.48). After adjustment for confounders, the RR for LBW infants was 12.31 (95% CI, 4.47, 33.89) among subjects with vitamin D deficiency and 3.15 (95% CI, 1.06, 9.39) among subjects with vitamin D insufficiency. Moreover, 16.01% of neonates were SGA infants among subjects with vitamin D deficiency (RR, 5.72; 95% CI, 3.80, 8.59) and 5.59% among subjects with vitamin D insufficiency (RR, 1.99; 95% CI, 1.27, 3.13). After adjustment for confounders, the RR for SGA infants was 6.47 (95% CI, 4.30, 9.75) among subjects with vitamin D deficiency and 2.01 (95% CI, 1.28, 3.16) among subjects with vitamin D insufficiency.
Conclusion:
Maternal vitamin D deficiency during pregnancy elevates the risk of SGA and LBW infants in a Chinese population.
Context:
There are a few prospective population-based cohort studies evaluating the effects of maternal thyroid dysfunctions on fetal and infant developments, but they are inconsistent.
Objective:
...The objective of the study was to investigate the effects of maternal thyroid dysfunction on fetal and infant development.
Setting and Participants:
The study was nested within a prospective population-based China-Anhui Birth Defects and Child Development study. A total of 1017 women with singleton pregnancies participated in this study. Maternal serum samples in the first 20 wk of pregnancy were tested for thyroid hormones (TSH and free T4). Pregnant women were classified by hormone status into percentile categories based on laboratory assay and were compared accordingly.
Main Outcomes:
Outcomes included fetal loss, malformation, birth weight, preterm delivery, fetal stress, neonatal death, and infant development.
Results:
Clinical hypothyroidism was associated with increased fetal loss, low birth weight, and congenital circulation system malformations; the adjusted odds ratios 95% confidence interval (CI) were 13.45 (2.54–71.20), 9.05 (1.01–80.90), and 10.44 (1.15–94.62), respectively. Subclinical hypothyroidism was associated with increased fetal distress, preterm delivery, poor vision development, and neurodevelopmental delay; the adjusted odds ratios (95% CI) were 3.65 (1.44–9.26), 3.32 (1.22–9.05), 5.34 (1.09–26.16), and 10.49 (1.01–119.19), respectively. Isolated hypothyroxinemia was related to fetal distress, small for gestational age, and musculoskeletal malformations; the adjusted odds ratios (95% CI) were 2.95 (1.08–8.05), 3.55 (1.01–12.83), and 9.12 (1.67–49.70), respectively. Isolated hyperthyroxinemia was associated with spontaneous abortion; the adjusted odds ratio (95% CI) was 6.02 (1.25–28.96). Clinical hyperthyroidism was associated with hearing dysplasia; the adjusted odds ratio (95% CI) was 12.14 (1.22–120.70).
Conclusions:
Thyroid dysfunction in the first 20 wk of pregnancy may result in fetal loss and dysplasia and some congenital malformations.
Cancer associated fibroblast (CAF) is a well-known microenvironment contributor for the development of hepatocellular carcinoma (HCC), while forkhead box (FOX) proteins are also critical to ...exacerbate HCC malignancy. However, whether FOX proteins are involved in the crosstalk between CAFs and HCC cells remains unclear. In the present study, we reveal that CAFs induce forkhead box Q1 (FOXQ1) expression, and N-myc downstream-regulated gene 1 (NDRG1) is therefore trans-activated to enhance HCC initiation. Intriguingly, pSTAT6/C-C motif chemokine ligand 26 (CCL26) signaling is induced by FOXQ1/NDRG1 axis, thus recruiting hepatic stellate cells (HSCs), the main cellular source of CAFs, to the tumor microenvironment. Thereby, tumor initiating properties are enhanced at least partly through a positive feedback loop between CAFs and HCC cells. Importantly, leflunomide, a pSTAT6 inhibitor that has been approved for the treatment of rheumatoid arthritis, significantly blocks the loop and HCC progression. High expression of CAF marker, ACTA2, and induced FOXQ1/NDRG1 axis in HCC tissues predict unfavorable prognosis. Collectively, our findings uncover a positive feedback loop between CAFs and FOXQ1/NDRG1 axis in neoplastic cells to drive HCC initiation, thus providing new potential therapeutic targets for HCC.
•FOXQ1/NDRG1 axis mediates CAF-HCC crosstalk to drive tumor initiation.•FOXQ1/NDRG1 axis activates pSTAT6/CCL26 signaling to recruit HSCs.•Leflunomide blockades HCC-CAFs crosstalk and suppresses HCC progression.
Display omitted
•Fe3O4, (α + γ)-Fe2O3 and α-Fe2O3 were firstly used for Cd immobilization in sediment.•(α + γ)-Fe2O3 possessed the best efficiency in Cd immobilization.•Three synthesized iron oxides ...effectively reduce mobile fraction of Cd in sediment.•The immobilization mechanism of three synthesized iron oxides on Cd were studied.
In situ immobilization remediation has attracted attention due to its effectiveness in treating contaminated sediment. In this study, the effects of three iron oxides with different crystallinities Fe3O4, (α + γ)-Fe2O3, and α-Fe2O3 were investigated as potential in situ amendments for Cd remediation in sediment. The three amendments were mixed with the sediment at dosages of 0%, 2%, and 6% (w/w) for 1–56 d of treatment. The changes of the oxidation-reduction potential (Eh) and pH in the treated sediment samples indicated the related mechanism for Cd immobilization. The experimental results showed that when the sediment sample was treated with synthesized iron oxides for 56 d, the TCLP (toxicity characteristic leaching procedure) leachable Cd in the sediment decreased by 29.43–57.26%, and the PBET (physiologically-based extraction test) extracted Cd decreased by 17.22–39.40%. Additionally, (α + γ)-Fe2O3 exhibited better performances than the other iron oxides. The BCR (Community Bureau of Reference) extraction, results suggested that synthetized iron oxides can effectively reduce the mobile fraction and increase the stable fraction of Cd, which in turn reduces the bioavailability of Cd in the sediment. The analysis of the Fe dissolution risk showed that a high dosage Fe3O4 treatment posed a potential threat to the organisms and suggested that the secondary Fe minerals were involved in the Cd immobilization. Overall, this study provides new insight into the potential applications of iron oxides for Cd immobilization in sediment.
Abstract
Background
With rapid economic development, the world's average life expectancy is increasing, leading to the increasing prevalence of osteoporosis worldwide. However, due to the complexity ...and high cost of dual-energy x-ray absorptiometry (DXA) examination, DXA has not been widely used to diagnose osteoporosis. In addition, studies have shown that the psoas index measured at the third lumbar spine (L3) level is closely related to bone mineral density (BMD) and has an excellent predictive effect on osteoporosis. Therefore, this study developed a variety of machine learning (ML) models based on psoas muscle tissue at the L3 level of unenhanced abdominal computed tomography (CT) to predict osteoporosis.
Methods
Medical professionals collected the CT images and the clinical characteristics data of patients over 40 years old who underwent DXA and abdominal CT examination in the Second Affiliated Hospital of Wenzhou Medical University database from January 2017 to January 2021. Using 3D Slicer software based on horizontal CT images of the L3, the specialist delineated three layers of the region of interest (ROI) along the bilateral psoas muscle edges. The PyRadiomics package in Python was used to extract the features of ROI. Then Mann–Whitney U test and the least absolute shrinkage and selection operator (LASSO) algorithm were used to reduce the dimension of the extracted features. Finally, six machine learning models, Gaussian naïve Bayes (GNB), random forest (RF), logistic regression (LR), support vector machines (SVM), Gradient boosting machine (GBM), and Extreme gradient boosting (XGBoost), were applied to train and validate these features to predict osteoporosis.
Results
A total of 172 participants met the inclusion and exclusion criteria for the study. 82 participants were enrolled in the osteoporosis group, and 90 were in the non-osteoporosis group. Moreover, the two groups had no significant differences in age, BMI, sex, smoking, drinking, hypertension, and diabetes. Besides, 826 radiomic features were obtained from unenhanced abdominal CT images of osteoporotic and non-osteoporotic patients. Five hundred fifty radiomic features were screened out of 826 by the Mann–Whitney U test. Finally, 16 significant radiomic features were obtained by the LASSO algorithm. These 16 radiomic features were incorporated into six traditional machine learning models (GBM, GNB, LR, RF, SVM, and XGB). All six machine learning models could predict osteoporosis well in the validation set, with the area under the receiver operating characteristic (AUROC) values greater than or equal to 0.8. GBM is more effective in predicting osteoporosis, whose AUROC was 0.86, sensitivity 0.70, specificity 0.92, and accuracy 0.81 in validation sets.
Conclusion
We developed six machine learning models to predict osteoporosis based on psoas muscle images of abdominal CT, and the GBM model had the best predictive performance. GBM model can better help clinicians to diagnose osteoporosis and provide timely anti-osteoporosis treatment for patients. In the future, the research team will strive to include participants from multiple institutions to conduct external validation of the ML model of this study.
PDF
