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1.
Eur J Nutr ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33394121

RESUMO

PURPOSE: Zinc is considered protective against atherosclerosis; however, the association between dietary zinc intake and cardiovascular disease remains debated. We investigated whether dietary zinc intake was associated with coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: This analysis included 5186 participants aged 61.9 ± 10.2 years (48.8% men; 41.3% white, 25.0% black, 21.6% Hispanic, and 12.1% Chinese American) from the MESA. Dietary zinc intake was assessed by a self-administered, 120-item food frequency questionnaire at baseline (2000-2002). Baseline and follow-up CAC were measured by computed tomography. CAC progression was defined as CAC > 0 at follow-up for participants with CAC = 0 at baseline; and an annualized change of 10 or percent change of ≥ 10% for those with 0 < CAC < 100 or CAC ≥ 100 at baseline, respectively. RESULTS: Dietary zinc intake was 8.4 ± 4.5 mg/day and 2537 (48.9%) of the included participants had CAC at baseline. Over a median follow-up of 3.4 years (25th-75th percentiles = 2.0-9.1 years), 2704 (52.1%) participants had CAC progression. In the fully adjusted model, higher dietary zinc was associated with a lower risk of CAC progression in both men (hazard ratio [HR] 0.697, 95% confidence interval [CI] 0.553-0.878; p = 0.002) and women (HR 0.675; 95% CI 0.496-0.919; p = 0.012, both comparing extreme groups). Furthermore, such an inverse association was attributable to dietary zinc intake from non-red meat (p < 0.05), rather than red meat sources (p > 0.05). CONCLUSIONS: In this multiethnic population free of clinically apparent cardiovascular disease, higher dietary zinc intake from non-red meat sources was independently associated with a lower risk of CAC progression. CLINICAL TRIAL REGISTRATION NUMBER: The MESA trial was registered at clinicaltrials.gov as NCT00005487.

2.
Methods Mol Biol ; 2191: 109-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32865742

RESUMO

Optogenetics provides a powerful approach for investigating neuronal electrophysiology at the scale required for drug discovery applications. Probing synaptic function with high throughput using optogenetics requires robust tools that enable both precise stimulation of and facile readout of synaptic activity. Here we describe two functional assays to achieve this end: (1) a pre-synaptic calcium assay that utilizes the channelrhodopsin, CheRiff, patterned optogenetic stimulus, and the pre-synaptically targeted calcium reporter jRGECO1a to monitor pre-synaptic changes in calcium influx and (2) a synaptic transmission assay in which CheRiff and cytosolic jRGECO1a are expressed in non-overlapping sets of neurons, enabling pre-synaptic stimulation and post-synaptic readout of activity. This chapter describes the methodology and practical considerations for implementation of these two assays.

3.
Biochem Pharmacol ; : 114353, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278350

RESUMO

BACKGROUND: Rho-Associated kinases ROCK1 and ROCK2 have been extensively investigated in the pathogenesis of cardiovascular disease. However, their roles are not fully understood in carcinogenesis. In this study, we investigated whether ROCK1 or ROCK2 is required for the survival and growth of hepatocellular carcinoma (HCC) cells and underlying mechanism. METHODS: ROCKs expression was determined in human HCC tissue and cell lines using qRT-PCR, western blotting, and immunohistochemistry (IHC). Cell growth and proliferation were assayed using cell counting kit-8 (CCK-8) and EdU incorporation assay. Cell cycle and apoptosis analysis were performed using flow cytometry. HCC cell division or mitosis was observed using a confocal microscope and a time relapse fluorescence microscope. Inhibitory role of targeting ROCK1/2 on HCC was assayed in both xenograft and primary HCC mouse models. RESULTS: Both ROCK1 and ROCK2 are over-expressed in human HCC tissues and cell lines. Knockdown of ROCK1 or ROCK2 inhibited HCC cell growth. Pharmacological inactivation of ROCK1/2 with Fasudil further blocked the growth and survival of HCC both in vitro and in vivo. Mechanically, Fasudil induces cell cycle arrest in HCC cells, but not apoptosis. Instead, Fasudil treatment led to mitotic catastrophe in HCC cells, characterized with the multipolar and asymmetric mitosis, and disassociated stress fibers. Knockdown of cofilin restored the cell morphology and division, and reduced the mitotic catastrophe induced by Fasudil. CONCLUSIONS: Both ROCK1 and ROCK2 are required for HCC cell division and growth. Targeting ROCK1 or ROCK2 rather than both can serve as a potential approach for HCC treatment and may reduce the side effects.

4.
ACS Omega ; 5(45): 29102-29109, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33225141

RESUMO

Rosin is a sustainable resource, which is mainly composed of resin acid. Rosin-modified resin is widely used in adhesives, inks, coatings, and other fields, and its stability is very important for the production, storage, and use of products. Thermal stability and reactivity of three resin acids (levopimaric acid, neoabietic acid, and dehydroabietic acid) and four rosin-modified resins were studied using an accelerating rate calorimeter (ARC). They are stable, and exothermic reactions do not occur even when they were heated to 200 °C under a nitrogen atmosphere, but they are unstable under an oxygen atmosphere. The mechanism of the oxidation reaction process was found: first, resin acids absorb oxygen, and then an exothermic oxidation occurs. The initial exothermic temperature (T 0) of levopimaric acid, neoabietic acid, and dehydroabietic acid are 354.01, 353.83, and 398.20 K, the initial oxidation kinetics shows a second-order reaction, and the activation energies (E a) are 42.90, 58.05, and 46.60 kJ/mol, respectively. Peroxide concentration of three resin acids were determined by iodometry. The T 0 values of hydrogenated rosin, disproportionated rosin, hydrogenated rosin glyceride, and hydrogenated rosin pentaerythritol ester, the four rosin-modified resin, are 353.71, 348.32, 412.85, and 412.44 K. Levopimaric acid and neoabietic acid have higher oxidative reactivity and easily undergoes an oxidation reaction at lower temperature. Rosin-modified resins are stable and find it difficult to undergo oxidation reactions.

5.
Regen Biomater ; 7(5): 505-514, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33149939

RESUMO

Various surface bioactivation technology has been confirmed to improve the osteogenic ability of porous titanium (pTi) implants effectively. In this study, a three-layered composite coating, i.e. outer layer of hydroxyapatite (HA), middle layer of loose titanium dioxide (L-TiO2) and inner layer of dense TiO2 (D-TiO2), was fabricated on pTi by a combined processing procedure of pickling, alkali heat (AH), anodic oxidation (AO), electrochemical deposition (ED) and hydrothermal treatment (HT). After soaking in simulated body fluid for 48 h, the surface of the AHAOEDHT-treated pTi was completely covered by a homogeneous apatite layer. Using MC3T3-E1 pro-osteoblasts as cell model, the cell culture revealed that both the pTi without surface treatment and the AHAOEDHT sample could support the attachment, growth and proliferation of the cells. Compared to the pTi sample, the AHAOEDHT one induced higher expressions of osteogenesis-related genes in the cells, including alkaline phosphatase, Type I collagen, osteopontin, osteoclast inhibitor, osteocalcin and zinc finger structure transcription factor. As thus, besides the good corrosion resistance, the HA/L-TiO2/D-TiO2-coated pTi had good osteogenic activity, showing good potential in practical application for bone defect repair.

6.
J Cell Mol Med ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33150736

RESUMO

It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)-enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α-SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3-MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate-activated protein kinase (AMPK) by Compound C attenuated Aldo/MR-enhanced VC. These results suggested that Aldo facilitates high Pi-induced VSMC osteogenic phenotypic switch and calcification through MR-mediated signalling pathways that involve AMPK-dependent autophagy, which provided new insights into Aldo excess-associated VC in various settings.

7.
Int J Mol Sci ; 21(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138174

RESUMO

Ribociclib (RIB, LE011, Kisqali®), an orally administered inhibitor of cyclin-dependent kinase-4/6 (CDK-4/6) complex, is clinically effective for the treatment of several malignancies, including advanced breast cancer. However, information regarding the effects of RIB on membrane ion currents is limited. In this study, the addition of RIB to pituitary tumor (GH3) cells decreased the peak amplitude of erg-mediated K+ current (IK(erg)), which was accompanied by a slowed deactivation rate of the current. The IC50 value for RIB-perturbed inhibition of deactivating IK(erg) in these cells was 2.7 µM. In continued presence of µM RIB, neither the subsequent addition of 17ß-estradiol (30 µM), phorbol 12-myristate 13-acetate (10 µM), or transforming growth factor-ß (1 µM) counteracted the inhibition of deactivating IK(erg). Its presence affected the decrease in the degree of voltage-dependent hysteresis for IK(erg) elicitation by long-duration triangular ramp voltage commands. The presence of RIB differentially inhibited the peak or sustained component of delayed rectifier K+ current (IK(DR)) with an effective IC50 of 28.7 or 11.4 µM, respectively, while it concentration-dependently decreased the amplitude of M-type K+ current with IC50 of 13.3 µM. Upon 10-s long membrane depolarization, RIB elicited a decrease in the IK(DR) amplitude, which was concomitant with an accelerated inactivation time course. However, the inability of RIB (10 µM) to modify the magnitude of the hyperpolarization-activated cation current was disclosed. The mean current-voltage relationship of IK(erg) present in HL-1 atrial cardiomyocytes was inhibited in the presence of RIB (10 µM). Collectively, the hyperpolarization-activated cation current was observed. RIB-mediated perturbations in ionic currents presented herein are upstream of its suppressive action on cytosolic CDK-4/6 activities and partly participates in its modulatory effects on the functional activities of pituitary tumor cells (e.g., GH3 cells) or cardiac myocytes (e.g., HL-1 cells).

8.
Sensors (Basel) ; 20(21)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126741

RESUMO

In this article, a new Binary Fully Convolutional Neural Network (B-FCN) based on Taguchi method sub-optimization for the segmentation of robotic floor regions, which can precisely distinguish floor regions in complex indoor environments is proposed. This methodology is quite suitable for robot vision in an embedded platform and the segmentation accuracy is up to 84.80% on average. A total of 6000 training datasets were used to improve the accuracy and reach convergence. On the other hand, to reach real-time computation, a PYNQ FPGA platform with heterogeneous computing acceleration was used to accelerate the proposed B-FCN architecture. Overall, robots would benefit from better navigation and route planning in our approach. The FPGA synthesis of our binarization method indicates an efficient reduction in the BRAM size to 0.5-1% and also GOPS/W is sufficiently high. Notably, the proposed faster architecture is ideal for low power embedded devices that need to solve the shortest path problem, path searching, and motion planning.

9.
World J Gastroenterol ; 26(37): 5629-5645, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33088157

RESUMO

BACKGROUND: Many natural products confer health benefits against diverse diseases through their antioxidant activities. Carbon tetrachloride (CCl4) is often used in animal experiments to study the effects of substances on liver injury and the related mechanisms of action, among which oxidative stress is a major pathogenic factor. AIM: To compare antioxidant and hepatoprotective activities of ten herbs and identify and quantify phytochemicals for the one with strongest hepatoprotection. METHODS: The antioxidant activity of ten medicinal herbs was determined by both ferric-reducing antioxidant power and Trolox equivalent antioxidant capacity assays. The total phenolic and flavonoid contents were determined by Folin-Ciocalteu method and aluminum chloride colorimetry, respectively. Their effects on CCl4-induced oxidative liver injury were evaluated and compared in a mouse model by administrating each water extract (0.15 g/mL, 10 mL/kg) once per day for seven consecutive days and a dose of CCl4 solution in olive oil (8%, v/v, 10 mL/kg). The herb with the strongest hepatoprotective performance was analyzed for the detailed bioactive components by using high-performance liquid chromatography-electrospray ionization source-ion trap tandem mass spectrometry. RESULTS: The results revealed that all tested herbs attenuated CCl4-induced oxidative liver injury; each resulted in significant decreases in levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and triacylglycerols. In addition, most herbs restored hepatic superoxide dismutase and catalase activities, glutathione levels, and reduced malondialdehyde levels. Sanguisorba officinalis (S. officinalis) L., Coptis chinensis Franch., and Pueraria lobata (Willd.) Ohwi root were the three most effective herbs, and S. officinalis L. exhibited the strongest hepatoprotective effect. Nine active components were identified in S. officinalis L. Gallic acid and (+)-catechin were quantified (7.86 ± 0.45 mg/g and 8.19 ± 0.57 mg/g dried weight, respectively). Furthermore, the tested herbs displayed a range of in vitro antioxidant activities proportional to their phenolic content; the strongest activities were also found for S. officinalis L. CONCLUSION: This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.

10.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120314838, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33115269

RESUMO

OBJECTIVE: To investigate whether low-carbohydrate diets (LCDs) were associated with coronary artery calcium (CAC) progression. Approach and Results: We included the participants who completed computed tomography assessment of baseline CAC in 2000 to 2001 (year 15) and follow-up (year 20 or 25) and food frequency questionnaire (years 0, 7, and 20) in the CARDIA study (Coronary Artery Risk Development in Young Adults). CAC progression was defined as CAC >0 at follow-up among participants with baseline CAC of 0 and an annualized change of 10 or percent change of ≥10% for those with 0

11.
Exp Biol Med (Maywood) ; : 1535370220963197, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023330

RESUMO

IMPACT STATEMENT: In this study, we explored the expression profile of lncRNA in HCC tumor tissues and paracancerous tissues using microarray assays. Furthermore, a new lncRNA (lnc-ATG9B-4) was identified, which was about 3.5 times more expressed in tumor tissues than in paracancerous tissues. Through clinicopathological analysis, lnc-ATG9B-4 was determined to be related to the tumorous size, TNM stages, portal vein tumor thrombus (PVTT), the tumor capsule, metastasis, and the degree of differentiation. Lnc-ATG9B-4 promoted the proliferation, invasion, as well as migration of the HCC cells by upregulating the expression of CDK5. Here, we further exploited the molecular mechanisms of lnc-ATG9B-4 to screen new drug intervention targets for recurrence and metastasis of HCC.

12.
Front Endocrinol (Lausanne) ; 11: 547356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101195

RESUMO

Purpose: Patients with primary aldosteronism (PA) have an increased risk of target-organ damage (TOD), but whether metabolic syndrome (MetS) is more prevalent and contributes to TOD in PA patients remains unresolved. We aimed to evaluate the associations between MetS profiles and TOD in Chinese PA individuals. Methods: Metabolic parameters and pre-clinical TOD including left ventricular hypertrophy, estimated glomerular filtration, and microalbuminuria; insulin sensitivity or resistance; and islet ß-cell function were assessed by the homeostasis models (HOMA-IR, HOMA-ß) and the other surrogate indexes [composite insulin sensitivity index (ISI), modified ß-cell function index (MBCI)] determined from the oral glucose tolerance test were compared in PA vs. matched essential hypertension (EH) patients. Results: A total of 109 PA patients and 109 essential hypertension (EH) controls individually matched for sex, age, and office systolic blood pressure and duration of hypertension were studied. The prevalence of MetS and its individual components in PA was significantly lower than in EH [MetS: 28 (25.6%) vs. 54 (49.5%), P < 0.001]. PA patients had a higher composite ISI but a lower HOMA-IR, HOMA-ß, and MBCI than EH controls (all P < 0.05). Concerning TOD, PA patients had significantly higher prevalence of microalbuminuria and left ventricular hypertrophy (LVH), and lower levels of estimated glomerular filtration (eGFR) than EH controls (all P < 0.05). On multivariate logistic regression analysis, female gender and elevated plasma aldosterone levels were significantly associated with TOD in PA. However, there were no significant associations between MetS and its individual components and TOD in PA patients. Conclusions: PA patients had a lower MetS prevalence but exhibited more severe TOD than matched EH controls. The study highlights the deleterious effects of aldosterone excess on the development of TOD, whereas MetS or its individual components might be less influential in PA.

13.
Int J Nanomedicine ; 15: 4171-4189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606671

RESUMO

Background: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects. Purpose: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro. Materials and Methods: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 pre-osteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments. Results: By controlling Si content in ~0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surface-coated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect. Conclusion: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.


Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Durapatita/farmacologia , Nanopartículas/química , Osteogênese , Próteses e Implantes , Silício/química , Titânio/farmacologia , Adsorção , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Camundongos , Nanopartículas/ultraestrutura , Nanotubos/química , Neovascularização Fisiológica/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Soroalbumina Bovina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios X
14.
Front Plant Sci ; 11: 950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676091

RESUMO

The phytohormone Abscisic acid (ABA) regulates plant growth, development, and responses to abiotic stresses, including senescence, seed germination, cold stress and drought. Several kinds of researches indicate that exogenous ABA can enhance artemisinin content in A. annua. Some transcription factors related to ABA signaling are identified to increase artemisinin accumulation through activating the artemisinin synthase genes. However, no prior study on ABA transporter has been performed in A. annua. Here, we identified a pleiotropic drug resistance (PDR) transporter gene AaPDR4/AaABCG40 from A. annua. AaABCG40 was expressed mainly in roots, leaves, buds, and trichomes. GUS activity is primarily observed in roots and the vascular tissues of young leaves in proAaABCG40: GUS transgenic A. annua plants. When AaABCG40 was transferred into yeast AD12345678, yeasts expressing AaABCG40 accumulated more ABA than the control. The AaABCG40 overexpressing plants showed higher artemisinin content and stronger drought tolerance. Besides, the expression of CYP71AV1 in OE-AaABCG40 plants showed more sensitivity to exogenous ABA than that in both wild-type and iAaABCG40 plants. According to these results, they strongly suggest that AaABCG40 is involved in ABA transport in A. annua.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32587833

RESUMO

The iron acquisition system is an essential virulence factor for human infection and is under tight regulatory control in a variety of pathogens. Ferric-uptake regulator (Fur) is one of Fe2+-responsive transcription factor that maintains iron homeostasis, and the regulator of capsule synthesis (Rcs) is known to regulate exopolysaccharide biosynthesis. We speculate the Rcs may involve in iron-acquisition given the identified regulator box in the upstream of entC that participated in the biosynthesis of enterobactin. To study the coregulation by RcsAB and Fur of entC, we measured the ß-galactosidase activity and relative mRNA expression of entC in WT and mutant strains. The RcsAB- and Fur-protected regions were identified by an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay. A regulatory cascade was identified with which Fur repressed rcsA expression and reduced RcsAB and entC expression. Our study demonstrated that entC was coregulated by two different transcriptional regulators, namely, RcsAB and Fur, in response to iron availability in Klebsiella pneumoniae.

16.
J Allergy Clin Immunol ; 146(1): 101-109.e1, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437740

RESUMO

BACKGROUND: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. OBJECTIVE: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester. METHODS: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. RESULTS: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. CONCLUSIONS: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.


Assuntos
Infecções por Coronavirus/imunologia , Recém-Nascido/imunologia , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Betacoronavirus , China , Feminino , Humanos , Subpopulações de Linfócitos/imunologia , Masculino , Pandemias , Gravidez , Terceiro Trimestre da Gravidez
17.
Am J Pathol ; 190(7): 1397-1413, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32283103

RESUMO

Hepatoblastoma (HB) is the most common pediatric liver tumor. Though Wnt/ß-catenin and Hippo cascades are implicated in HB development, studies on crosstalk between ß-catenin and Hippo downstream effector transcriptional coactivator with PDZ-binding motif (TAZ) in HB are lacking. Expression levels of TAZ and ß-catenin in human HB specimens were assessed by immunohistochemistry. Functional interplay between TAZ and ß-catenin was determined by overexpression of an activated form of TAZ (TAZS89A), either alone or combined with an oncogenic form of ß-catenin (ΔN90-ß-catenin), in mouse liver via hydrodynamic transfection. Activation of TAZ often co-occurred with that of ß-catenin in clinical specimens. Although the overexpression of TAZS89A alone did not induce hepatocarcinogenesis, concomitant overexpression of TAZS89A and ΔN90-ß-catenin triggered the development of HB lesions exhibiting both epithelial and mesenchymal features. Mechanistically, TAZ/ß-catenin-driven HB development required TAZ interaction with transcriptional enhanced associate domain factors. Blockade of the Notch cascade did not inhibit TAZ/ß-catenin-dependent HB formation in mice but suppressed the mesenchymal phenotype. Neither Yes-associated protein nor heat shock factor 1 depletion affected HB development in TAZ/ß-catenin mice. In human HB cell lines, silencing of TAZ resulted in decreased cell growth, which was further reduced when TAZ knockdown was associated with suppression of either ß-catenin or Yes-associated protein. Overall, our study identified TAZ as a crucial oncogene in HB development and progression.


Assuntos
Carcinogênese/metabolismo , Hepatoblastoma/metabolismo , Neoplasias Hepáticas/metabolismo , Transativadores/metabolismo , beta Catenina/metabolismo , Animais , Criança , Pré-Escolar , Feminino , Hepatoblastoma/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos
18.
J Clin Virol ; 127: 104356, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302955

RESUMO

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing an outbreak of pneumonia in Wuhan, Hubei Province, China, and other international areas. OBJECTIVE: Here, we report the clinical characteristics of the newborns delivered by SARS-CoV-2 infected pregnant women. METHODS: We prospectively collected and analyzed the clinical features, laboratory data and outcomes of 7 newborns delivered by SARS-CoV-2 infected pregnant women in Zhongnan Hospital of Wuhan University during January 20 to January 29, 2020. RESULTS: 4 of the 7 newborns were late preterm with gestational age between 36 weeks and 37 weeks, and the other 3 were full-term infants. The average birth weight was 2096 ± 660 g. All newborns were born without asphyxia. 2 premature infants performed mild grunting after birth, but relieved rapidly with non-invasive continuous positive airway pressure (nCPAP) ventilation. 3 cases had chest X-ray, 1 was normal and 2 who were supported by nCPAP presented mild neonatal respiratory distress syndrome (NRDS). Samples of pharyngeal swab in 6 cases, amniotic fluid and umbilical cord blood in 4 cases were tested by qRT-PCR, and there was no positive result of SARS-CoV-2 nucleic acid in all cases. CONCLUSIONS: The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats.


Assuntos
Infecções por Coronavirus/diagnóstico , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Líquido Amniótico/virologia , Betacoronavirus , Peso ao Nascer , China/epidemiologia , Pressão Positiva Contínua nas Vias Aéreas , Infecções por Coronavirus/epidemiologia , Feminino , Sangue Fetal/virologia , Idade Gestacional , Humanos , Saúde do Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Gravidez , Estudos Prospectivos , Medição de Risco , Tórax/diagnóstico por imagem , Tórax/virologia , Tomografia Computadorizada por Raios X
19.
Am J Pathol ; 190(7): 1414-1426, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32275903

RESUMO

Cholestatic liver injury may lead to a series of hepatobiliary syndromes, which can progress to cirrhosis and impaired liver regeneration, eventually resulting in liver-related death. Mammalian target of rapamycin complex 2 (mTORC2) is a major regulator of liver metabolism and tumor development. However, the role of mTORC2 signaling in cholestatic liver injury has not been characterized to date. In this study, we generated liver-specific Rictor knockout mice to block the mTORC2 signaling pathway. Mice were treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to induce cholestatic liver injury. DDC feeding induced cholestatic liver injury and ductular reaction as well as activation of the mTORC2/Akt signaling pathway in wild-type mice. Loss of mTORC2 led to significantly decreased oval cell expansion after DDC feeding. Mechanistically, this phenotype was independent of mTORC1/fatty acid synthase cascade (Fasn) or yes-associated protein (Yap) signaling. Notch pathway was instead strongly inhibited during DDC-induced cholestatic liver injury in liver-specific Rictor knockout mice. Furthermore, mTORC2 deficiency in adult hepatocytes did not inhibit ductular reaction in this cholestatic live injury mouse model. Our results indicated that mTORC2 signaling effectively regulates liver regeneration by inducing oval cell proliferation. Liver progenitor cells or bile duct cells, rather than mature hepatocytes, would be the major source of ductular reaction in DDC-induced cholestatic liver injury.


Assuntos
Colestase/metabolismo , Hepatopatias/metabolismo , Regeneração Hepática/fisiologia , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Transdução de Sinais/fisiologia , Animais , Ductos Biliares/metabolismo , Colestase/fisiopatologia , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatopatias/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco/metabolismo
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