Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the ...underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.
The present study was conducted to investigate the effects of high dietary lipid levels on growth, metabolism, antioxidant capacity, and immune responses of largemouth bass. Fish (initial body weight ...13.38 ± 0.11 g) were fed three isonitrogenous semi-purified diets containing 5%, 10%, and 20% lipid, respectively. The results indicated that fish fed 10% lipid diet showed significantly better final body weight, specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) compared with that fed 5% lipid diet. Meanwhile, fish fed 20% lipid diet had a significantly higher viscera ratio (VR), hepatosomatic index (HSI), intraperitoneal fat ratio (IPF), and liver lipid content than those fed the other diets. Higher alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) contents, and LDL-C/HDL-C value in plasma were recorded in fish fed 20% lipid diet, while higher insulin contents were obtained in fish fed 5% lipid diet. In addition, the highest carnitine palmitoyltransferase I (CPT1), AMP-activated protein kinase (AMPK), fructose-1,6-bisphosphatase (FBPase), and phosphoenolpyruvate carboxykinase (PEPCK) activities in the liver were also observed in fish fed 20% lipid diet. However, fish fed 20% lipid diet had a significantly lower superoxide dismutase (SOD) and catalase (CAT) activities and higher MDA contents in liver than those fed the other diets. The higher nitric oxide (NO) contents and inducible nitric oxide synthase (iNOS) activity in liver were recorded in fish fed 10% lipid diet. Moreover, the alkaline phosphatase (ALP), inducible nitric oxide synthase (iNOS) and lysozyme activities, and nitric oxide (NO) contents in plasma were higher in fish fed the 10% diets than the other groups. In conclusion, high dietary lipid levels could suppress growth performance and liver anti-oxidative capacity, and reduce immune responses of largemouth bass
.
In this paper, we have developed a simple, fast, convenient and sensitive method for determination of organophosphorus pesticides in real samples based on inhibition mechanism of acetylcholinesterase ...(AChE). The biosensor is composed of enzymes (AChE and ChOx (choline oxidase)), QDs and acetylcholine (ACh), without any complex process of assembly for biosensor. After the experimental conditions are optimized, the limit of detection (LOD) for dichlorvos (DDVP) is found to be 4.49nM. Two linear ranges allow a wide determination of DDVP concentration from 4.49nM to 6780nM. Furthermore, a possible mechanism is put forward to explain the fluorescence quenching of CdTe QDs in the presence of H2O2. More importantly, the obtained biosensor is proven to be suitable for the detection of residues of organophosphorus pesticides (OPs) in real examples. The excellent performance of this biosensor will facilitate future development of rapid and high-throughput detection of organophosphorus pesticides.
•A simple and fast biosensor for detection of OPs was proposed.•The biosensor does not need any complex process of assembly and pretreatment.•A possible mechanism is put forward on the fluorescence quenching of CdTe QDs.•The biosensor is suitable for the detection of residues of OPs in real examples.
Androgen deprivation therapy (ADT) is the major treatment for metastatic prostate cancer (PCa), but few studies have investigated the effects of ADT on thyroid diseases.
This population-based, ...nationwide cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) with 17,192 PCa patients between 1997 and 2013. We used the Cox proportional hazards models and propensity score-matched analysis to analyze the association between ADT and the development of thyroid diseases.
A total of 17,192 newly diagnosed men with PCa were selected from the NHIRD. There were 6200 ADT users and 6200 non-ADT users after 1:1 propensity score matching. There was a significantly decreased risk of thyroid diseases among ADT users compared with non-ADT users (adjusted hazard ratio (aHR): 0.79, 95% confidence interval (CI): 0.65-0.95, p < 0.001). Further analysis showed a significantly decreased risk of thyroid diseases with increasing ADT duration (p < 0.001).
The result showed that ADT use in men with PCa was associated with a decreased risk of thyroid disease development.
In this work, we demonstrated that the quinone structure can quench the fluorescence of the carbon dots （CDs）. The sensitive determination of dopamine （DA） was studied primarily based on this ...principle. DA would be transformed into DA quinone under alkaline conditions, which resulted in fluorescence quenching of the CDs. A good linear range from 5 nmol/L to 0.4 mmol/L was obtained and the detection limit was 1 nmol/L. Moreover, the quenching effect of quinone structure on the fluores- cence of CDs was confirmed by Fourier transform infrared spectra, time-correlated single-photon counting and X-ray photoelectron spectroscopy. Remarkably, CDs were firstly applied to detect the quinone drugs quantitatively which contained typical quinone structure based on the quenching mechanism. More than this, the sensing platform was demonstrated to provide credible selectivity and satisfac- tory stability in human serum solution with good linerrange. Hence, our practical application and mechanism have showed great potential for diagnostic purposes.
DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of ...breast cancer.
We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath's method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters.
The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29-0.92), the third (HR: 0.49; 95%CI: 0.27-0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20-0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14-0.74). In the full follow-up dataset, similar results were obtained.
DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit.
The γ/γ’ phase interface, being the main plane defect in nickel-based single-crystal superalloys, can have a significant effect on the microstructural stability and mechanical properties of ...superalloys. To improve the thermodynamic stability and fracture strength of the γ-Ni/γ’-Ni
3
Al interface and gain insight into the underlying micro-mechanisms, the segregation tendency of 12 alloying elements
X
at the γ-Ni/γ’-Ni
3
Al interface and their effects on the interfacial formation and Griffith fracture works were investigated by using first-principles calculations. It is found that all alloying elements
X
can segregate to the corner-point site of the γ-Ni (001) layer except the element Y. The Re-, Ti-, Mo-, W-, Cr-, Nb-, Ta-, Hf- and Zr-segregated interfaces are more stable than the unalloyed interface due to the presence of pseudogap and lower values of densities of states at the Fermi level. The segregation of Ru, Co, Re, Mo, W, Cr, Nb and Ta strengthens the interfacial fracture strength, which can be mainly attributed to the enhanced bonding strengths of
X
–Ni bonds formed in these segregated interfaces. The interfacial segregation of Cr, Re, Mo, W, Nb and Ta can not only improve the thermodynamic stability but also enhance the fracture strength of the phase interface. The segregation of Ta and Re is able to improve the thermodynamic stability and fracture strength of the γ-Ni/γ’-Ni
3
Al interface to the maximum extent, respectively.
Graphic abstract
The effect of interfacial segregation of alloying elements on the fracture strength and thermodynamic stability of the γ-Ni/γ’-Ni
3
Al phase interface and the underlying mechanisms are studied.
Abstract Mesoporous hollow silica nanoparticles (MHSNs) are emerging as one of the new and promising nanomaterials for biomedical applications, but the biocompatibility of MHSNs in vivo has received ...little attention. In the present study, the systematic single and repeated dose toxicity, biodistribution and clearance of MHSNs in vivo were demonstrated after intravenous injection in mice. For single dose toxicity, lethal dose 50 (LD50 ) of 110 nm MHSNs was higher than 1000 mg/kg. Further repeated dose toxicity studies indicated no death was observed when mice were exposed to MHSNs at 20, 40 and 80 mg/kg by continuous intravenous administration for 14 days. These results suggest low toxicity of MHSNs when intravenous injection at single dose or repeated administrations. ICP–OES and TEM results show that the MHSNs mainly accumulate in mononuclear phagocytic cells in liver and spleen. In addition, these particles could be excreted from the body and the entire clearance time of the particles should be over 4 weeks. These findings would be useful for future development of nanotechnology-based drug delivery system and other biomedical applications.
The selenylated polysaccharides chemically belong to the organic Se-conjugated macromolecules and have recently been attracting more and more attention due to their potential to promote body health ...or prevent cancers. Longan (
L.), as a subtropical fruit, contains soluble and non-digestible polysaccharides that are regarded with health care functions in the body. In this study, the longan polysaccharides (LP) were obtained via enzyme-assisted water extraction, and then chemically selenylated using a reaction system composed of HNO
-Na
SeO
to yield two selenylated products, namely, SeLP1 and SeLP2, with Se contents of 1.46 and 4.79 g/kg, respectively. The anti-cancer effects of the three polysaccharide samples (LP, SeLP1, and SeLP2) were thus investigated using the human colon cancer HT-29 cells as the cell model. The results showed that SeLP1 and SeLP2 were more able than LP to inhibit cell growth, alter cell morphology, cause mitochondrial membrane potential loss, increase intracellular reactive oxygen and Ca
levels, and induce apoptosis via regulating the eight apoptosis-related genes and proteins including Bax, caspases-3/-8/-9, CHOP, cytochrome c, DR5, and Bcl-2. It was thereby proven that the selenylated polysaccharides could induce cell apoptosis via activating the death receptor, mitochondrial-dependent, and ER stress pathways. Collectively, both SeLP1 and SeLP2 showed higher activities than LP in HT-29 cells, while SeLP2 was consistently more active than SeLP1 in exerting these assessed anti-cancer effects on the cells. In conclusion, this chemical selenylation covalently introduced Se into the polysaccharide molecules and caused an enhancement in their anti-cancer functions in the cells, while higher selenylation extent was beneficial to the activity enhancement of the selenylated products.
The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on ...liver injury induced by carbon tetrachloride (CCl
) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl
(15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl
-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl
-induced injury by resisting oxidative stress and protecting mitochondrial function.
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