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1.
J Hazard Mater ; 401: 123374, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32653792

RESUMO

In this work, novel NiSiO@NiAlFe layered double hydroxides (LDHs) hollow spheres were prepared by hydrothermal method. It was worth noting that LDHs' grafting towards NiSiO hollow spheres could avoid the LDHs' aggregation, and thus enhanced the material's adsorption capacity. Furthermore, adsorption kinetics, adsorption isotherms, and Box-Behnken Design (BBD) model were conducted. Results indicated that NiSiO@NiAlFe LDHs hollow spheres had sufficient adsorption capability towards Cs+. The adsorption kinetics satisfied the pseudo-second-order adsorption model, Temkin model and Langmuir isotherm model. The adsorption process was efficient at the alkaline condition (pH = 10). The adsorption kinetics indicated that the adsorption process could reach the equilibrium in only 20 min. The maximum adsorption capacity of Cs+ towards NiSiO@NiAlFe LDHs hollow spheres was estimated to be 61.5 mg g-1. Moreover, the adsorption thermodynamics indicated that the adsorption process was exothermal, feasible and spontaneous. Thus, NiSiO@NiAlFe LDHs hollow spheres presented a broad potential for treating cesium containing wastewater.

2.
J Agric Food Chem ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054205

RESUMO

Garcinia mangostana L. (mangosteen) is a famous tropical fruit that contains a large number of xanthones. Regular consumption of mangosteen may confer health benefits and prevent some diseases, such as malaria. Quinone reductase 2 (QR-2) is a cytosolic enzyme found in human red blood cells, and it is becoming a target for chemoprevention because it is involved in the mechanisms of several diseases, including malaria. To understand whether the xanthones present in mangosteen might inhibit the activity of QR-2, blood samples were collected from rat following the oral administration of mangosteen extract and then incubated with QR-2 followed by UF-HPLC-QTOF/MS analysis to rapidly screen for and identify the QR-2-inhibiting xanthones. A total of 16 xanthones were identified, and six of these (α-mangostin, γ-mangostin, 8-deoxyartanin, 1,3,7-trihydroxy-2,8-di(3-methylbut-2-enyl)xanthone, garcinone E, and 9-hydroxycalabaxanthone) were subjected to QR-2 inhibition assay. γ-Mangostin exhibited the strongest inhibition, achieving an IC50 value of 3.82 ± 0.51 µM. Its interaction with QR-2 was found to involve hydrogen bond and arene-arene interaction as revealed by molecular docking. The present study could provide new insight into the potential application of mangosteen as functional food ingredients for inhibiting the activity of QR-2. However, the extent of daily intake of mangosteen required and the exact contribution of mangosteen to the prevention and treatment of malaria remain subjects of further study.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33021404

RESUMO

Background - Non-pulmonary vein (NPV) trigger has been reported as an important predictor of recurrence post-atrial fibrillation (AF) ablation. Elimination of NPV triggers can reduce the recurrence of post-ablation AF. Deep learning was applied to pre-ablation pulmonary vein computed tomography (PVCT) geometric slices to create a prediction model for NPV triggers in patients with paroxysmal atrial fibrillation (PAF). Methods - We retrospectively analyzed 521 PAF patients who underwent catheter ablation of PAF. Among them, PVCT geometric slices from 358 non-recurrent AF patients (1-3 mm interspace per slice, 20-200 slices for each patient, ranging from the upper border of the left atrium to the bottom of the heart, for a total of 23683 images of slices) were used in the deep learning process, the ResNet34 of the neural network, to create the prediction model of the NPV trigger. There were 298 (83.2%) patients with only pulmonary vein (PV) triggers and 60 (16.8%) patients with NPV triggers +/- PV triggers. The patients were randomly assigned to either training, validation or test groups and their data was allocated according to those sets. The image datasets were split into training (n=17340), validation (n=3491), and testing (n=2852) groups, which had completely independent sets of patients. Results - The accuracy of prediction in each PVCT image for NPV trigger was up to 82.4±2.0%. The sensitivity and specificity were 64.3±5.4% and 88.4±1.9%, respectively. For each patient, the accuracy of prediction for a NPV trigger was 88.6±2.3%. The sensitivity and specificity were 75.0±5.8% and 95.7±1.8%, respectively. The area under the curve (AUC) for each image and patient were 0.82±0.01 and 0.88±0.07, respectively. Conclusions - The deep learning model using pre-ablation PVCT can be applied to predict the trigger origins in PAF patients receiving catheter ablation. The application of this model may identify patients with a high risk of NPV trigger before ablation.

4.
Kaohsiung J Med Sci ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022863

RESUMO

Diabetic retinopathy (DR) is a common complication of diabetes mellitus. Inflammatory responses play crucial roles in the progress of DR. Long noncoding RNA (lncRNAs) and microRNAs (miRNAs) are key signal transduction molecules in retina, and tightly connected with DR occurrence and development. Our study aimed to explore the functions of lncRNA H19, miR-19b and silence information regulator factor related enzymes 1 (SIRT1) in the progress of DR. Retinal pigment epithelial cells (ARPE-19) were used to build high-glucose (HG) model. Quantitative real-time PCR (qPCR) was performed to detect expression of H19, miR-19b and SIRT1 at normal glucose (NG) and HG conditions. And western blotting was performed to test protein level of SIRT1. QPCR and enzyme-linked immunosorbent assay were performed to detect expression of inflammatory cytokines. Finally, the interactions among H19, miR-19b and SIRT1 were determined by dual-luciferase reporter assay. Our results showed that lncRNA H19 and SIRT1 were reduced, while miR-19b was increased in ARPE-19 cells with HG condition. MiR-19b positively regulated the expression of inflammatory cytokines, including TNF-α, IL-1ß and IL-6. Inhibition of miR-19b and overexpression of H19 inhibited the expression of inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, while knockdown of SIRT1 reversed their effects on inflammatory cytokines. Furthermore, overexpression of miR-19b reversed the inhibitory effects of overexpression of H19 on inflammatory cytokines. Importantly, H19 targeted miR-19b to downregulate miR-19b expression. Furthermore, miR-19b bound to SIRT1 and declined SIRT1 expression. H19/miR-19b/SIRT1 axis plays a key role of HG-induced inflammatory response in ARPE-19 cells, which provides new targets for DR treatment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33105013

RESUMO

There is a delayed (lag 1 to 2 days) correlation between acute PM 2.5 (particulate matter < 2.5 µm in aerodynamic diameter) exposure and cardiovascular events, but the underlying mechanism remained unclear. We aimed to investigate the delayed impact of acute PM 2.5 exposures on cardiac autonomics through linear and nonlinear heart rate variability (HRV) analyses. Among 6912 patients who had received 24-h Holter ECG between October 1, 2015, to October 31, 2016, 56 patients (31 males, 70.3 ± 12.7 years old) were enrolled. We classified the patients as high (> 35.4 µg/m3) or low (< 35.4 µg/m3) PM 2.5 groups according to their PM 2.5 exposures on the day of Holter recordings (day 0) lag 1 and lag 2 days. Linear and nonlinear HRV parameters〔Detrended fluctuation analysis (DFA) slopes 1 and 2〕were compared. Baseline characteristics were similar between groups. Linear and nonlinear HRV parameters were similar between high- and low-exposure groups on day 0 and lag 1 day, respectively. However, DFA slope 1 was significantly lower in the high-exposure group on lag 2 days (0.784 ± 0.201 vs. 0.964 ± 0.274, p = 0.021). DFA slope 1 of the high-exposure group was significantly lower on daytime periods (9 am to 9 pm, 8 am to 4 pm and 4 pm to 12 pm) but not on nighttime periods. High lag 2 days PM 2.5 exposure is associated with low DFA slope 1 and the relationship is diurnal. This suggests that air pollution might have a delayed impact on the cardiovascular autonomic system.

6.
Thromb Haemost ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33099284

RESUMO

The coronavirus disease 2019 (COVID-19) is our latest pandemic, preceded by the H1N1 swine flu in 2009, which lasted approximately 19 months. One of the special characteristics of COVID-19 is the propensity to cause venous thromboembolism (VTE). Thromboinflammation seems to play a prominent role in the pathogenesis. We will here review some mechanisms in the pathogenesis and discuss some hematological biomarkers, and also whether they serve as useful risk factors for VTE. The role of general risk assessment models for medically ill patients specifically in COVID-19 is appraised. The type of prophylaxis and particularly whether standard or augmented doses of chemoprophylaxis should be used is reviewed based on available evidence. We are also comparing recommendations from 10 different guidance or position/consensus statements. Treatment recommendations for patients with COVID-19 and pulmonary embolism are discussed with current general treatment guidelines as reference. Specifics for patients with COVID-19 are pointed out and the potential role of thrombolytic treatment is explored.

7.
Biomed Res Int ; 2020: 7176169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083482

RESUMO

Background: Bronchopulmonary dysplasia (BPD) is a common and serious complication in premature infants. Lung fibroblasts (LFs) are present in the extracellular matrix and participate in pulmonary development in response to BPD. The aim of this study was to investigate the effect of extracellular signal-regulated kinase (ERK) on LFs cultured from newborn rats. Material and Methods. Primary LFs were isolated and treated with epidermal growth factor (EGF, 20 ng/mL) in the presence or absence of an ERK inhibitor, PD98059 (10 µmol/L). Phosphorylated ERK1/2 (p-ERK1/2) protein levels were determined using immunocytochemistry, western blotting, and real-time reverse transcription quantitative (RT-q)PCR. LF proliferation was examined by flow cytometry and a cell counting kit-8 assay. LF transdifferentiation was examined by protein and mRNA expression of α-smooth muscle actin (α-SMA) by immunocytochemistry, western blotting, and RT-qPCR. LF migration was examined by the transwell method. Results: Phosphorylated ERK1/2, which was activated by EGF, promoted LF proliferation by accelerating cell-cycle progression from the G1 to S phase. After treatment with PD98059, the expression of p-ERK1/2 in LFs, cellular proliferation, and the percentage of cells in S phase were significantly decreased. Phosphorylated ERK1/2 also promoted the differentiation of LFs into myofibroblasts through increased α-SMA synthesis and migration. Conclusion: The activation of ERK promotes proliferation, transdifferentiation, and migration of lung fibroblasts from newborn rats.

8.
Medicine (Baltimore) ; 99(41): e22673, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031334

RESUMO

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (<2.35-fold upper limit of normal range) was 95.2% and decreased to 65.5% for patients with higher PRL level.In conclusion, our results suggest existence of potentially alternative mechanisms underlying hyperprolactinemia in NFPAs, like the discrepancy of sex and age and the negative feedback of FT4. Preoperative PRL is a predictor for postoperative PRL normalization, which is of clinically relevant for postoperative management of NFPAs.


Assuntos
Adenoma/complicações , Hiperprolactinemia/etiologia , Neoplasias Hipofisárias/complicações , Adenoma/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1119-1124, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059811

RESUMO

OBJECTIVE: To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. METHODS: The mice at different developmental stages were enrolled, including fetal mice (embryonic days 14.5 and 18.5), neonatal mice (0, 3, 7, 14, and 21 days old), young mice (28 and 42 days old), and adult mice (84 days old). The lung tissues of all fetal mice from 4 pregnant mice were collected at each time point in the fetal group. Four mice were sampled in other age groups at each time point. Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. RESULTS: The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. It increased gradually after birth, reached a peak on day 3 after birth, and reached a nadir on day 14 after birth (P<0.05). The expression of AGT reached a peak on days 0 and 7 after birth and reached a nadir on day 21 after birth (P<0.05). The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). Agtr1a expression reached a peak on day 21 after birth (P<0.05). Agtr2 expression gradually decreased to a low level after birth. Renin, Agtr1b, and Mas1 showed low expression in lung tissues at all developmental stages. CONCLUSIONS: At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. The other key molecules of the RAS pathway have their own expression patterns. These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.


Assuntos
Fatores Etários , Infecções por Coronavirus/patologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Animais , Animais Recém-Nascidos , Betacoronavirus , Feminino , Feto , Pulmão/metabolismo , Pulmão/virologia , Camundongos , Pandemias , Gravidez , Sistema Renina-Angiotensina
10.
IEEE Trans Cybern ; PP2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33095734

RESUMO

Multiple modality clustering seeks to partition objects via leveraging cross-modality relations to provide comprehensive descriptions of the same objects. Current clustering methods rely heavily on accurate affinity measurements among samples. The samplewise affinity is costive to be constructed yet easy to corrupt by the heterogeneous gap. In the era of big data, fast and accurate clustering of multiple modality data remains challenging. To fill the gap, we propose a novel approach to achieve the clustering by focusing on feature matching across different modalities instead of samplewise affinity. First, a feature matching matrix is calculated by measuring the potential featurewise correlations. The obtained matching matrix is decomposed into two bases corresponding to the column and row spaces of feature matching, acting as coded bases within feature spaces of the different modalities. Then, the sample assignment is obtained by jointly reconstructing the samples by the two bases. The feature matching potential and sample assignment are collaboratively learned by an alternating optimization scheme. The proposed method dramatically reduces the computational cost by avoiding the costive samplewise affinity estimation, without sacrificing accuracy. Extensive experiments on the synthetic and real-world datasets demonstrate its superior speed and high accuracy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33078325

RESUMO

PURPOSE: Reports concerning clinical characteristics of cor triatriatum and approaches for catheter ablation of complex atrial tachyarrhythmias remain limited. Here, we describe successful catheter ablation treatments for complex atrial tachyarrhythmias in patients with cor triatriatum and address the clinical caveats. METHODS: Demographic characteristics, electrophysiologic findings, and ablation results in four patients with cor triatriatum were described. RESULTS: Catheter ablation was performed in four patients with cor triatriatum (three sinister and one dexter) and complex atrial arrhythmias (three with persistent atrial fibrillation (AF) and one with atypical left atrial flutter). A transseptal puncture was selectively directed into the accessory compartment containing the pulmonary veins. A comprehensive preview involving transthoracic echocardiography, transesophageal echocardiography, and computed tomography of the pulmonary veins was critical for proper positioning of ablation catheters. The pulmonary veins remain the major triggers or initiators for AF, and four pulmonary vein isolation procedures were sufficient to achieve successful results with negative inducibility test in the patients with AF. Heterogeneous conduction and complex fractionated signals were observed on the fibromuscular membrane. Atypical flutter was terminated during ablation over the connection between membrane and left atrial roof. The procedure was successfully performed on all patients without complications. No acute recurrences of atrial tachyarrhythmias were observed in any of the patients during short-term follow-up. CONCLUSIONS: Catheter ablation is a feasible and efficient therapeutic strategy for treating complex atrial tachyarrhythmias in patients with cor triatriatum. Atrial remodeling due to anatomical obstruction or heterogeneous conduction of the fibromuscular membrane may serve as an arrhythmic substrate.

12.
Environ Pollut ; 268(Pt A): 115628, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049484

RESUMO

Air pollution is an important risk factor for autoimmune diseases, but its association with the recurrence of rheumatoid arthritis (RA) remains unclear so far. This study aimed to investigate the short-term association between traffic-related air pollutants and hospital readmissions for RA in Hefei, China. Data on daily hospital readmissions for RA and traffic-related air pollutants, including particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and carbon monoxide (CO), from 2014 to 2018 were retrieved. A time-series approach using generalized linear regression model was employed. The analysis was further stratified by sex, age and season. A total of 1153 readmissions for RA were reported during the study period. A significant association between high-concentration PM2.5 (90th percentile) and RA readmissions was observed on lag1 (relative risk (RR) = 1.09, 95% confidence interval (CI): 1.01-1.19) and lasted until lag3 (RR = 1.06, 95%CI: 1.01-1.12). From lag2 to lag5, high-concentration NO2 (90th percentile) was associated with increased risk of RA readmissions, with the highest RR observed at lag 4 (1.11, 95%CI: 1.05-1.17). Stratified analyses indicated that females and the elderly appeared to be more vulnerable to high-concentration PM2.5 and NO2 exposure. High-concentration PM2.5 and NO2 in cold seasons were consistently significantly associated with increased risk of RA readmissions. Exposure to high-concentration PM2.5 and NO2 was associated with increased risk of RA readmissions. Protective measures against the exposure to high-concentration PM2.5 and NO2 should be taken to reduce the recurrence risk in RA patients, especially in females, the elderly and during cold seasons.

13.
Phys Med Biol ; 65(20): 205001, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33027063

RESUMO

To develop and evaluate a deep learning method to segment parotid glands from MRI using unannotated MRI and unpaired expert-segmented CT datasets. We introduced a new self-derived organ attention deep learning network for combined CT to MRI image-to-image translation (I2I) and MRI segmentation, all trained as an end-to-end network. The expert segmentations available on CT scans were combined with the I2I translated pseudo MR images to train the MRI segmentation network. Once trained, the MRI segmentation network alone is required. We introduced an organ attention discriminator that constrains the CT to MR generator to synthesize pseudo MR images that preserve organ geometry and appearance statistics as in real MRI. The I2I translation network training was regularized using the organ attention discriminator, global image-matching discriminator, and cycle consistency losses. MRI segmentation training was regularized by using cross-entropy loss. Segmentation performance was compared against multiple domain adaptation-based segmentation methods using the Dice similarity coefficient (DSC) and Hausdorff distance at the 95th percentile (HD95). All networks were trained using 85 unlabeled T2-weighted fat suppressed (T2wFS) MRIs and 96 expert-segmented CT scans. Performance upper-limit was based on fully supervised MRI training done using the 85 T2wFS MRI with expert segmentations. Independent evaluation was performed on 77 MRIs never used in training. The proposed approach achieved the highest accuracy (left parotid: DSC 0.82 ± 0.03, HD95 2.98 ± 1.01 mm; right parotid: 0.81 ± 0.05, HD95 3.14 ± 1.17 mm) compared to other methods. This accuracy was close to the reference fully supervised MRI segmentation (DSC of 0.84 ± 0.04, a HD95 of 2.24 ± 0.77 mm for the left parotid, and a DSC of 0.84 ± 0.06 and HD95 of 2.32 ± 1.37 mm for the right parotid glands).

14.
Curr Pharm Des ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33030126

RESUMO

BACKGROUND: Meteorin-like (Metrnl) is a newly identified adipokine implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), yet data on the circulating levels of Metrnl in patients with T2DM are controversial. To derive a more precise estimation on circulating Metrnl levels in T2DM patients, we conducted this meta-analysis. METHODS: The existing studies on the circulating levels of Metrnl in patients with T2DM published up to 16 January 2020 were comprehensively retrieved from PubMed, Web of Science, EMBASE, and The Cochrane library database. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated using random-effects model. Heterogeneity was assessed and quantified by Cochrane's Q and I2 statistic. All statistical analyses were performed using Stata 12.0 software. RESULTS: Nine studies with 867 T2DM patients and 831 normal glucose tolerance (NGT) controls were included in the final analysis according to the inclusion criteria. No significant difference in circulating Metrnl levels was found between T2DM patients and NGT individuals (pooled SMD = -0.429, 95% CI = -1.077 to 0.219). Compared to controls, circulating Metrnl levels were significantly higher in the subgroups with BMI <25 kg/m2, using plasma sample and patient sample size ≥100, while circulating Metrnl levels were significantly lower in subgroups with age ≤50 years and homeostatic model assessment for insulin resistance (HOMA-IR) ≥4. CONCLUSIONS: This meta-analysis indicates no significant change in circulating Metrnl levels in T2DM patients. However, this result may be influenced by age, BMI, sample type, HOMA-IR and patients sample size. Further longitudinal studies are warranted to offer more insights into the relationship between Metrnl and T2DM.

15.
Hepatol Int ; 14(5): 733-742, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32886333

RESUMO

BACKGROUND AND AIMS: Liver injury is found in some of patients with COVID-19. Liver injury of COVID-19 patients based on severity grading and abdominal radiological signs have not been reported until now. The aim of our study is to determine clinical profiles of the patients based on severity grading, describe abdominal radiological signs, and investigate the correlations of the severity with clinical profiles and radiological signs. METHODS: This retrospective cohort study included 115 patients with COVID-19 from Jan 2020 to Feb 2020. Medical records of the patients were collected and CT images were reviewed. RESULTS: Common clinical manifestations of patients with COVID-19 were fever (68.70%), cough (56.52%), fatigue (31.30%); some of them had gastrointestinal symptoms (diarrhea, 12.17%; nausea or vomiting 7.83%; inappetence, 7.83%). Abnormal liver function was observed in some of patients with COVID-19. Significant differences in the levels of AST, albumin,CRP were observed among different groups classified by the severity. Common findings of upper abdominal CT scan were liver hypodensity (26.09%) and pericholecystic fat stranding (21.27%); liver hypodensity was more frequently found in critical cases (58.82%). The severity of COVID-19 correlated with semi-quantitative CT score of pulmonary lesions, CT-quantified liver/spleen attenuation ratio in patients with COVID-19. CONCLUSIONS: Some of the patients with COVID-19 displayed liver damage revealed by liver functional tests and upper abdominal CT imaging, and the severity of COVID-19 patients correlated with some of liver functional tests and CT signs; thus, it will allow an earlier identification of high-risk patients for early effective intervention.

16.
ACS Synth Biol ; 9(10): 2808-2818, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-32911927

RESUMO

Chinese hamster ovary (CHO) cells are the predominant cell chassis for biopharmaceutical production. Engineering cellular pathways related to cell death, metabolism, and glycosylation in CHO cells is desired but challenging. Here, we present a novel approach that exploits CRISPR-Cas13d for gene silencing and CHO cell engineering. CRISPR-Cas13d is a burgeoning system that exploits Cas13d nuclease and guide RNA (gRNA) for RNA cleavage and gene knockdown. We first showed that CRISPR-Cas13d effectively knocked down exogenous genes in CHO cell lines (K1, DG44, and DUXB11) commonly used for recombinant protein production. We next demonstrated that CRISPR-Cas13d robustly suppressed the expression of exogenous genes and various endogenous genes involved in gene amplification, apoptosis, metabolism, and glycosylation (e.g., GS, BAK, BAX, PDK1, and FUT8) in CHO cells with efficiencies ranging from 60% to 80%, simply by transient transfection. By integrating the entire CRISPR-Cas13d system with the Sleeping Beauty system and optimal gRNA design, we further improved the knockdown efficiency and rapidly generated stable cells with ≈80%-90% knockdown. With this approach, we knocked down FUT8 expression for >90% and significantly attenuated the IgG fucosylation. These data altogether implicated the potentials of CRISPR-Cas13d for gene regulation, glycoengineering, and cell engineering of CHO cells.

17.
Chem Biodivers ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940397

RESUMO

A systematically chemical investigation of Citrus changshan-huyou Y.B.Chang resulted in the isolation and structure determination of twelve known natural products, including limonoid, nootkatone, scoparone, ß-sitosterol, 3,3',4',5,6,7,8,-heptamethoxyflavone, nobiletin, tangeretin, naringin, hesperidin, neohesperidin, 3,5-dihydroxyphenyl ß-D-glucoside, ß-sitosterol-D-glucoside. The structure modification of the most abundant compound limonin further led to eight limonoid derivatives, including epi-limonol, epi-limonyl acetate, and six new compounds epi-limonol A, limonol A, limonol B, epi-limonol B, epi-limonol C, epi-limonol D, which enlarged the chemical diversity of limonin related limonoids. The structures of the new limonoid derivatives were identified by extensive spectroscopic analysis. In bioassay, all the isolates, the semi-synthetic derivatives and the previously isolated limonoids in our natural product library were subjected for anti-inflammatory activities evaluation, and several limonoids exhibited the inhibition of TNF-α release.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32995955

RESUMO

PURPOSE: The regulatory T cells (Tregs) are a subpopulation of lymphocytes that suppress the immune responses. The prognostic value of Tregs in lymphoma patients remains controversial. Thus, we conducted this meta-analysis to clarify the role of Tregs in the prognosis of lymphoma patients. METHODS: We searched PubMed, Embase, and Web of Science to obtain eligible studies that evaluated the prognostic factor of Tregs for lymphoma patients. Hazards ratios (HRs) with the matching 95% confidence intervals (95%CIs) were merged to estimate the prognostic value of Tregs. RESULTS: We finally retrieved 23 eligible studies, including a total of 2269 patients. The overall pooled analysis on all types of lymphomas showed that Tregs had a significantly positive association with prolonged overall survival (OS) (HR = 0.633, 95% CI 0.528-0.758) and progression-free survival (PFS) (HR = 0.451, 95% CI 0.261-0.779). Subgroup analysis indicated that high Tregs were significantly correlated with longer OS in Hodgkin lymphoma, diffuse large B cell lymphoma, and natural killer/T cell lymphoma. However, there was no significant association of Tregs with T cell lymphoma and follicular lymphoma. CONCLUSIONS: Increased Tregs indicates a better prognosis for patients with lymphoma. Tregs could be used as a valuable prognostic biomarker of lymphoma patients.

19.
J Thromb Haemost ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32865293

RESUMO

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) especially refractory and (or) relapsed ITP, is a serious and global health burden and its clinical treatment is far from being satisfied. Hetrombopag is a novel, small-molecule thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura (CITP). OBJECTIVES: This first-in-patient study aimed to investigate the safety, pharmacokinetics, and anticipated therapeutic dose of hetrombopag in CITP patients. METHODS: In this multicenter, first-in-patient study, CITP patients received hetrombopag in a dose escalation (2.5 mg/day, 5 mg/day, or 7.5 mg/day) cohort. All patients received hetrombopag in fasting condition once daily for 2 weeks. RESULTS: Of 44 patients screened, 32 were enrolled and treated. Most adverse events were graded 1 to 2 (ie, mild to moderate), and the incidence and severity were similar for three study cohorts. The pharmacokinetics of hetrombopag were found to be nonlinear with greater than dose-proportional: 12.5% of patients (1/8) in the 2.5 mg/d cohort, 58.3% of patients (7/12) in the 5 mg/d cohort, 66.7% of patients (8/12) in the 7.5 mg/d cohort reached the primary study endpoint of a platelet count exceeding 50 × 109 /L on day 28. CONCLUSION: Hetrombopag was well tolerated and preliminarily efficacious. Efficacy, safety, and pharmacokinetic data suggest that 7.5 mg hetrombopag once daily was the anticipated therapeutic dose of hetrombopag in CITP patients and has been recommended for investigation in a later confirmatory clinical study of hetrombopag.

20.
Int J Obes (Lond) ; 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32921796

RESUMO

BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. COVID-19 patients demonstrated significantly different outcomes in clinic. We aimed to figure out whether obesity is a risk factor influencing the progression and prognosis of COVID-19. METHODS: 95 patients with COVID-19 were divided into obesity group and non-obesity group according to their body mass index (BMI). The demographic data, clinical characteristics, laboratory examination, and chest computed tomography (CT) were collected, analyzed and compared between two groups. RESULTS: Our data showed that COVID-19 patients with obesity had more underlying diseases and higher mortality rate compared to those without obesity. Furthermore, patients with obesity also demonstrated more severe pathological change in lung and higher blood lymphocytes, triglycerides, IL-6, CRP, cystatin C, alanine aminotransferase (ALT), erythrocyte sedimentation rate (ESR), which may greatly influence disease progression and poor prognosis of COVID-19. CONCLUSIONS: It suggest that obesity contributes to clinical manifestations and may influence the progression and prognosis of COVID-19 and it is considered as a potential risk factor of the prognosis of COVID-19. Special medical care and appropriate intervention should be performed in obesity patients with COVID-19 during hospitalization and later clinical follow-up, especially for those with additional other comorbidities.

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