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1.
Child Abuse Negl ; 104: 104470, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32234639

RESUMO

BACKGROUND: The impact of positive coping style on non-suicidal self-injury in adolescents remains unclear, while negative coping style increases the risk of non-suicidal self-injury (NSSI). There is less investigation on gender differences in the impacts of positive coping style and negative coping style on NSSI. It is unknown whether the impacts vary with different levels of adverse childhood experiences (ACEs). AIMS: To identify gender differences in the impacts of positive coping style and negative coping style on NSSI, and investigate the impacts at different levels of ACEs. METHOD: An adolescent health survey was conducted in 15 schools in China between November 2013 and January 2014. 9704 students aged 11-19 years completed standard questionnaires to record the details of coping style, NSSI and ACEs. RESULTS: 38.5 % of adolescents had ≥1 NSSI over the past 12 months. NSSI was significantly increased with the low positive coping style in girls with ≥3 ACEs, but not with 0 and 1-2 ACEs, and not in boys with any levels of ACEs. NSSI was increased with high negative coping style in both girls and boys across all ACEs. The negative coping style impact was stronger in girls than in boys (odds ratio 1.66, p < 0.05), especially in those with 1-2 ACEs. CONCLUSIONS: Adolescents at high risk of NSSI in relation to coping styles should be targeted accordingly. Reducing negative coping style in girls and boys and improving positive coping style in girls who have high ACEs could help prevent NSSI in adolescents.

2.
Brain Struct Funct ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32246242

RESUMO

This study sought to determine if reducing dopamine D1 receptor (D1R) expression in the dorsal striatum (DS) via RNA-interference alters methamphetamine self-administration. A lentiviral construct containing a short hairpin RNA (shRNA) was used to knock down D1R expression (D1RshRNA). D1RshRNA in male rats increased responding for methamphetamine (i.v.) under a fixed-ratio schedule in an extended access paradigm, compared to D1R-intact rats. D1RshRNA also produced a vertical shift in a dose-response paradigm and enhanced responding for methamphetamine in a progressive-ratio schedule, generating a drug-vulnerable phenotype. D1RshRNA did not alter responding for sucrose (oral) under a fixed-ratio schedule compared to D1R-intact rats. Western blotting confirmed reduced D1R expression in methamphetamine and sucrose D1RshRNA rats. D1RshRNA reduced the expression of PSD-95 and MAPK-1 and increased the expression of dopamine transporter (DAT) in the DS from methamphetamine, but not sucrose rats. Sucrose density gradient fractionation was performed in behavior-naïve controls, D1RshRNA- and D1R-intact rats to determine the subcellular localization of D1Rs, DAT and D1R signaling proteins. D1Rs, DAT, MAPK-1 and PSD-95 predominantly localized to heavy fractions, and the membrane/lipid raft protein caveolin-1 (Cav-1) and flotillin-1 were distributed equally between buoyant and heavy fractions in controls. Methamphetamine increased localization of PSD-95, Cav-1, and flotillin-1 in D1RshRNA and D1R-intact rats to buoyant fractions. Our studies indicate that reduced D1R expression in the DS increases vulnerability to methamphetamine addiction-like behavior, and this is accompanied by striatal alterations in the expression of DAT and D1R signaling proteins and is independent of the subcellular localization of these proteins.

3.
Biol Reprod ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32219310

RESUMO

Genital tubercle has bisexual potential before sex differentiation. Females exposed to androgen during sex differentiation show masculinized external genitalia, but the effects of different androgens on tubular urethral and penile formation in females are mostly unknown. In this study, we compared the masculinization effects of commonly used androgens methyltestosterone, dihydrotestosterone and testosterone on the induction of penile formation in females. Our results suggested that prenatal treatment with low doses of methyltestosterone, but not same doses of dihydrotestosterone or testosterone could induce penile formation in female mice. The minimum dose of dihydrotestosterone and testosterone for inducing tubular urethral formation in female mice was respectively 50 and 20 times higher than that of methyltestosterone. In vivo methyltestosterone treatment induced more nuclear translocation of androgen receptors in genital tubercles of female mice, affected Wnt signaling gene expressions, and then led to similar patterns of cell proliferation and death in developing genital tubercles to those of control males. We further revealed that low-dose methyltestosterone, but not same dose of dihydrotestosterone or testosterone treatment induced penile formation in female guinea pigs. Exposure of organ culture to methyltestosterone, dihydrotestosterone or testosterone could induce nuclear translocation of androgen receptors in genital tubercle of female mouse suggested the differential effect of the three androgens in vivo might be due to the hormonal profile in mother or fetus, rather than the local genital tissue. To understand the differential role of these androgens in masculinization process involved is fundamental to androgen replacement therapy for diseases related to external genital masculinization.

4.
Medicine (Baltimore) ; 99(13): e19665, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221094

RESUMO

The aim of this study was to investigate the relationship between blood lipid level and the parameters of embryo morphology of in vitro fertilization (IVF).A total of 488 patients undergoing conventional IVF were divided into pregnant (n = 286) and nonpregnant (n = 202) groups. Levels of triglycerides (TG), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoprotein (LDL), lipoprotein (a), lipoprotein (b), and embryo outcomes were studied. Spearman correlation was performed to analyze the correlation between blood lipid levels and embryo quality in pregnant group.The normal fertilization rate and number of good quality embryos were higher than nonpregnant group (P < .05). TG, TC, and LDL levels were negatively correlated with number of normal fertilized oocytes, while TG, TC, and Lp(b) were negatively correlated with number of good quality embryos. TG level was negatively correlated with number of oocytes and cleavage embryos while HDL and Lp(a) were positively correlated with number of oocytes, normal fertilized oocytes and cleavage embryos (P < .05).TG, TC, LDL, and Lp(b) levels had negative correlation with embryo quality, while HDL and Lp(a) had positive correlation with the embryo quality. Our present findings showed blood lipid levels may provide certain reference for the prediction of IVF pregnancy outcome.

5.
EMBO J ; : e103111, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187724

RESUMO

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.

6.
J Biol Chem ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198183

RESUMO

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent non-tumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

7.
Theranostics ; 10(7): 3293-3307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194869

RESUMO

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD). Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer. In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV. Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development. Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV. Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro. Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development. Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro. cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects. The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo. cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro. cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1). Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro. Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients. Conclusions: This study provided novel insights into the molecular pathogenesis of CNV. The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.

8.
J Mater Chem B ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186318

RESUMO

An antibacterial Ag nanocluster-based hydrogel (Ag NC@BC) is prepared by the in situ formation of Ag NCs on the nanofibers of a natural bacterial-cellulose (BC) hydrogel. The Ag NC@BC exhibits superior, broad-spectrum antimicrobial performance against both Gram-positive and Gram-negative bacteria, and has a long-acting bactericidal efficacy compared to pristine Ag NCs due to its controlled-release feature for Ag species. Moreover, this fabricated hydrogel also possesses excellent biocompatibility. All of these advantages of Ag NC@BC endow it with great potentials in battling bacterial infections.

9.
Cell Death Dis ; 11(3): 197, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198344

RESUMO

The Shwachman-Bodian Diamond syndrome (SBDS)-associated gene, SBDS, is involved in rRNA synthesis and ribosome maturation, but the role of SBDS in cancer is largely elusive. In this study, we found that SBDS is often overexpressed or amplified in human cancers, and high level of endogenous SBDS is significantly associated with unfavorable prognosis. Conversely, knockdown of SBDS leads to p53 stabilization and activation through the ribosomal stress-RPL5/RPL11-MDM2 pathway, resulting in the repression of cancer cell proliferation and invasion. Interestingly, ectopic SBDS in the nucleoplasm also suppresses tumor cell growth and proliferation in vitro and in vivo. Mechanistically, ectopically expressed SBDS triggered by, for example, ribosomal stress binds to the transactivation domain of p53 and perturbs the MDM2-p53 interaction, consequently leading to impaired p53 ubiquitination and proteasomal degradation. Altogether, our finding for the first time demonstrates the dual functions of SBDS in cancer development by coordinating ribosome biogenesis and p53 activity.

10.
Oncol Lett ; 19(4): 2785-2792, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32218831

RESUMO

Lung squamous cell carcinoma (LUSC) progression is accompanied by changes in protein levels that may be reflected in body fluids, such as plasma, bronchoalveolar lavage fluid (BALF) and urine. Certain proteins present in these biofluids can facilitate lung cancer diagnosis. Kininogen 1 (KNG1), osteopontin (OPN) and α-1-antitrypsin (AAT) are associated with tumorigenesis. The present study aimed to explore the combined monitoring of plasma, urine and BALF to gain insight into LUSC by monitoring the levels of the above three protein using ELISA. LUSC (n=31) and healthy controls with benign lung diseases (n=20) were enrolled in the study. KNG1 levels in plasma, BALF and urine were significantly higher in patients with LUSC patients than in controls (P<0.0001, P<0.0001 and P=0.0010, respectively). OPN was upregulated in the plasma and BALF of patients with LUSC relative to controls (P=0.0107 and P=0.0004, respectively), whereas its levels in the urine of healthy controls were significantly higher (P=0.0088). Patients with LUSC had higher AAT levels in plasma, BALF and urine compared with those of the controls (P=0.0022, P=0.0014 and P=0.0005, respectively). Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.81 for KNG1 in plasma, 0.91 in BALF and 0.81 in urine. The AUC for OPN was 0.71 in plasma, 0.83 in BALF and 0.75 in urine. The AUC for AAT was 0.74 in plasma, 0.74 in BALF and 0.86 in urine. Immunohistochemical staining in 20 paired LUSC and adjacent normal tissues showed that KNG1, OPN and AAT levels were higher in LUSC tissues. Therefore, our results showed that KNG1, OPN and AAT in biofluids might be useful for the diagnosis of LUSC. These markers in urine and BALF may be better than in plasma for detecting LUSC.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32196850

RESUMO

Controlled synthesis of single-walled carbon nanotubes (SWNTs) is important for further application of carbon nanotubes. SWNT horizontal arrays with specific chirality can be enriched using carbide solid catalysts on substrates. However, it remains a big challenge to increase the production by continuous loading the carbide solid catalysts on substrates. Herein, we develop a rational approach to prepare floating carbide solid catalyst (FSC) for the controlled growth of SWNTs. Titanium carbide (TiC) nanoparticle FSC was directly obtained in the carrier gas phase by decomposition and carbonization of titanocene dichloride precursor at high-temperature. Using the TiC nanoparticles FSC, SWNTs horizontal arrays or randomly distributed networks were obtained depending on the collecting substrates. The chirality of the as-grown SWNTs were thermodynamically controlled to have four-fold symmetry, the same as (2 0 0) plane of face-centered cubic TiC. Further optimization of growth condition resulted in an abundance of (16, 8) tubes with ~74% content. This FSC chemical vapor deposition (FSCCVD) method is potential for realizing mass growth of SWNTs with controlled structures.

12.
Nucl Med Biol ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32169304

RESUMO

INTRODUCTION: Blood-brain barrier (BBB) disruption and subsequent neuro-inflammation occur following traumatic brain injury (TBI), resulting in a spectrum of human nervous system disorders. [99mTc]Tc-tilmanocept is a receptor-binding radiopharmaceutical FDA-approved for sentinel lymph node mapping. We hypothesize that after an intravenous (i.v.) injection, [99mTc]Tc-tilmanocept, will traverse a disrupted BBB and bind to CD206-bearing microglial cells. METHODS: Age-matched mice were divided into three groups: 5-days post TBI (n = 4), and 5-days post sham (n = 4), and naïve controls (n = 4). IRDye800CW-labeled [99mTc]Tc-tilmanocept (0.15 nmol per gram body weight) and FITC-labeled bovine serum albumin (FITC-BSA) were injected (i.v.) into each mouse. Mice were imaged with a high-resolution gamma camera for 45 min. Immediately after imaging, the brains were perfused with fixative, excised, imaged with a fluorescence scanner, assayed for radioactivity, and prepared for histology. RESULTS: In vivo nuclear imaging, ex vivo fluorescence imaging, ex vivo gamma well counting, and histo-microscopy demonstrated enhanced tilmanocept uptake in the TBI region. The normalized [99mTc]Tc-tilmanocept uptake value from nuclear imaging and the maximum pixel intensity from fluorescence imaging of the TBI group (1.12 ±â€¯0.12 and 2288 ±â€¯278 a.u., respectively) were significantly (P < 0.04) higher than the sham group (0.64 ±â€¯0.28 and 1708 ±â€¯101 a.u., respectively) and the naive group (0.76 ±â€¯0.24 and 1643 ±â€¯391 a.u., respectively). The mean [99mTc]Tc-tilmanocept scaled uptake in the TBI brains (0.058 ±â€¯0.013%/g) was significantly (P < 0.010) higher than the scaled brain uptake of the sham group (0.031 ±â€¯0.011%/g) and higher (P = 0.04) than the uptake of the naïve group (0.020 ±â€¯0.002%/g). Fluorescence microscopy demonstrated increased uptake of the IRDye800CW-tilmanocept and FITC-BSA in the TBI brain regions. CONCLUSION: [99mTc]Tc-tilmanocept traverses disrupted blood-brain barrier and localizes within the injured region. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [99mTc]Tc-tilmanocept could serve as an imaging biomarker for TBI-associated neuroinflammation and any disease process that involves a disruption of the blood-brain barrier.

13.
J Diabetes ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32119184

RESUMO

BACKGROUND: This study aimed to evaluate the discriminative abilities of glycosylated hemoglobin (HbA1c) and to examine the optimal HbA1c cutoff values for diabetes and prediabetes in Chinese adults. METHODS: Data of a population-based cohort of Chinese adults aged ≥40 years living in Jiading District in Shanghai were used. At baseline, 9389 and 7241 participants were included to identify the optimal HbA1c cutoff values for diabetes and prediabetes, respectively using the 1999 World Health Organization criteria as reference. In addition, the follow-up data on incident diabetes of 4538 participants were used to determine the HbA1c cutoff value for prediabetes using the development of diabetes as reference. The discriminative abilities of HbA1c were evaluated using receiver operating characteristic (ROC) curves, and the optimal cutoff values were determined by Youden's index. RESULTS: The areas under the ROC curves were 0.849 for diabetes, 0.614 for prediabetes using baseline data, and 0.648 for prediabetes using follow-up data. An HbA1c cutoff value of 6.0% had the largest Youden's index to diagnose diabetes with a sensitivity of 70.2% and a specificity of 87.4%. An HbA1c cutoff value of 5.6% was indicated for prediabetes using both baseline and follow-up data. However, the sensitivity and specificity were both low (55.4% and 61.1% using an oral glucose tolerance test as reference, 64.6% and 57.1% using incident diabetes as reference). CONCLUSIONS: An HbA1c value ≥6.0% could be used to detect diabetes in Chinese adults aged ≥40 years. However, although an HbA1c value of 5.6% to 5.9% was indicated in this study, the overall discrimination of HbA1c for prediabetes was poor. HIGHLIGHTS: A glycosylated hemoglobin (HbA1c) value ≥6.0% could be used to detect diabetes in Chinese adults aged ≥40 years. Although an HbA1c value of 5.6% to 5.9% was indicated to detect prediabetes in the current study using both cross-sectional and follow-up data, the overall discrimination of HbA1c for prediabetes was poor.

14.
Transl Oncol ; 13(3): 100741, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32092673

RESUMO

Acquired resistance and intrinsic to sorafenib therapy represents a major hurdle in improving the management of advanced hepatocellular carcinoma (HCC), which has been recently shown to be associated with the emergence of liver cancer stem cells (CSCs). However, it remains largely unknown whether and how histone posttranslational modifications, especially H3K27me3, are causally linked to the maintenance of self-renewal ability in sorafenib-resistant HCC. Here, we found that NOTCH1 signaling was activated in sorafenib-resistant HCC cells and NOTCH1 activation conferred hepatoma cells sorafenib resistance through enhanced self-renewal and tumorigenecity. Besides, the overexpression of EZH2 was required for the emergence of cancer stem cells following prolonged sorafenib treatment. As such, modulating EZH2 expression or activity suppressed activation of NOTCH1 pathway by elevating the expression of NOTCH1-related microRNAs, hsa-miR-21-5p and has-miR-26a-1-5p, via H3K27me3, and consequently weakened self-renewal ability and tumorigenecity and restored the anti-tumor effects of sorafenib. Overall, our results highlight the role of EZH2/NICD1 axis, and also suggest that EZH2 and NOTCH1 pathway are rational targets for therapeutic intervention in sorafenib-resistant HCC.

15.
Asian J Psychiatr ; 49: 101961, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32078954

RESUMO

Little is known about the sex differences in the determinants of suicide attempt among adolescents. The results from 14,820 students in China revealed that girls who were in younger age (10-13y), living in urban area, having lower social support and exposed to physical abuse were more likely to report SA compared to their boys counterparts. Conversely, the impact of having psychological symptoms on SA was stronger in boys than girls. Our findings highlight the importance that groups at highest risk of SA should be targeted accordingly by sex.

16.
Magn Reson Imaging ; 68: 136-147, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32045635

RESUMO

This paper proposes a multi-channel image reconstruction method, named DeepcomplexMRI, to accelerate parallel MR imaging with residual complex convolutional neural network. Different from most existing works which rely on the utilization of the coil sensitivities or prior information of predefined transforms, DeepcomplexMRI takes advantage of the availability of a large number of existing multi-channel groudtruth images and uses them as target data to train the deep residual convolutional neural network offline. In particular, a complex convolutional network is proposed to take into account the correlation between the real and imaginary parts of MR images. In addition, the k-space data consistency is further enforced repeatedly in between layers of the network. The evaluations on in vivo datasets show that the proposed method has the capability to recover the desired multi-channel images. Its comparison with state-of-the-art methods also demonstrates that the proposed method can reconstruct the desired MR images more accurately.

17.
Cell Death Dis ; 11(2): 104, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029710

RESUMO

Caveolin-1 (CAV1) is a crucial regulator of lipid accumulation and metabolism. Previous studies have shown that global Cav1 deficiency affects lipid metabolism and hepatic steatosis. We aimed to analyze the consequences of hepatocyte-specific Cav1 knockout under healthy conditions and upon non-alcoholic fatty liver disease (NAFLD) development. Male and female hepatocyte-specific Cav1 knockout (HepCAV1ko) mice were fed a methionine/choline (MCD) deficient diet for 4 weeks. MCD feeding caused severe hepatic steatosis and slight fibrosis. In addition, liver function parameters, i.e., ALT, AST, and GLDH, were elevated, while cholesterol and glucose level were reduced upon MCD feeding. These differences were not affected by hepatocyte-specific Cav1 knockout. Microarray analysis showed strong differences in gene expression profiles of livers from HepCAV1ko mice compared those of global Cav1 knockout animals. Pathway enrichment analysis identified that metabolic alterations were sex-dimorphically regulated by hepatocyte-specific CAV1. In male HepCAV1ko mice, metabolic pathways were suppressed in NAFLD, whereas in female knockout mice induced. Moreover, gender-specific transcription profiles were modulated in healthy animals. In conclusion, our results demonstrate that hepatocyte-specific Cav1 knockout significantly altered gene profiles, did not affect liver steatosis and fibrosis in NAFLD and that gender had severe impact on gene expression patterns in healthy and diseased hepatocyte-specific Cav1 knockout mice.

18.
J Vis Exp ; (155)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32009653

RESUMO

The occasional direct transmission of the highly pathogenic avian influenza A virus H5N1 (HPAI H5N1) and H7N9 to humans and their lethality are serious public health issues and suggest the possibility of an epidemic. However, our molecular understanding of the virus is rudimentary, and it is necessary to study the biological properties of its envelope proteins as therapeutic targets and to develop strategies to control infection. We developed a solid viral pseudotyped particle (pp) platform to study avian influenza virus, including the functional analysis of its hemagglutinin (HA) and neuraminidase (NA) envelope glycoproteins, the reassortment characteristics of the HAs and NAs, receptors, tropisms, neutralizing antibodies, diagnosis, infectivity, for the purposes of drug development and vaccine design. Here, we describe an experimental procedure to establish pps with the envelope glycoproteins (HA, NA) from two influenza A strains (HAPI H5N1 and 2013 avian H7N9). Their generation is based on the capacity of some viruses, such as murine leukemia virus (MLV), to incorporate envelope glycoproteins into a pp. In addition, we also detail how these pps are quantified with RT-qPCR, and the infectivity detection of native and mismatched virus pps depending on the origin of the HAs and NAs. This system is highly flexible and adaptable and can be used to establish viral pps with envelope glycoproteins that can be incorporated in any other type of enveloped virus. Thus, this viral particle platform can be used to study wild viruses in many research investigations.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32012021

RESUMO

Breast density is widely adopted to reflect the likelihood of early breast cancer development. Existing methods of mammographic density classification either require steps of manual operations or achieve only moderate classification accuracy due to the limited model capacity. In this study, we present a radiomics approach based on dilated and attention-guided residual learning for the task of mammographic density classification. The proposed method was instantiated with two datasets, one clinical dataset and one publicly available dataset, and classification accuracies of 88.7% and 70.0% were obtained, respectively. Although the classification accuracy of the public dataset was lower than the clinical dataset, which was very likely related to the dataset size, our proposed model still achieved a better performance than the naive residual networks and several recently published deep learning-based approaches. Furthermore, we designed a multi-stream network architecture specifically targeting at analyzing the multi-view mammograms. Utilizing the clinical dataset, we validated that multi-view inputs were beneficial to the breast density classification task with an increase of at least 2.0% in accuracy and the different views lead to different model classification capacities. Our method has a great potential to be further developed and applied in computer-aided diagnosis systems.

20.
Oxid Med Cell Longev ; 2020: 9585047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104545

RESUMO

Quercetin, a flavonoid found in fruits and vegetables, is widely distributed as a secondary metabolite in the plant kingdom. Oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). The present study investigated the effects of quercetin dietary supplementation on streptozotocin- (STZ-) induced hyperglycemic Arbor Acre (AA) broilers by determining the levels of fasting blood glucose (FBG), fasting insulin (FINS), biochemical indicators, oxidative stress markers, inflammatory cytokines content, antioxidant enzymes activities in tissues, and mRNA expression of genes relating to the insulin signaling pathway. Three hundred one-day-old healthy AA broilers were randomly assigned into 5 treatments; A, control healthy broilers; B, STZ-induced broilers; C, STZ-induced broiler dietary supplemented with 0.02% quercetin; D, STZ-induced broiler dietary supplemented with 0.04% quercetin; and E, STZ-induced broiler dietary supplemented with 0.06% quercetin. The results showed that quercetin supplementation relieved the side effects of STZ-induced oxidative stress by changing activities of antioxidant enzymes, decreasing malondialdehyde (MDA) and nitric oxide (NO) levels, activating expression of genes relating to PI3K/PKB signaling pathway that modulate glucose metabolism and reduce oxidative damage, thereby decreasing FBG and increasing FINS levels. These findings suggest that quercetin exhibits a protective effect in STZ-induced hyperglycemic AA broilers via decreasing oxidative stress.

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