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1.
Brief Bioinform ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140820

RESUMO

Effective drug discovery contributes to the treatment of numerous diseases but is limited by high costs and long cycles. The Quantitative Structure-Activity Relationship (QSAR) method was introduced to evaluate the activity of a large number of compounds virtually, reducing the time and labor costs required for chemical synthesis and experimental determination. Hence, this method increases the efficiency of drug discovery. To meet the needs of researchers to utilize this technology, numerous QSAR-related web servers, such as Web-4D-QSAR and DPubChem, have been developed in recent years. However, none of the servers mentioned above can perform a complete QSAR modeling and supply activity prediction functions. We introduce Cloud 3D-QSAR by integrating the functions of molecular structure generation, alignment, molecular interaction field (MIF) computing and results analysis to provide a one-stop solution. We rigidly validated this server, and the activity prediction correlation was R2 = 0.934 in 834 test molecules. The sensitivity, specificity and accuracy were 86.9%, 94.5% and 91.5%, respectively, with AUC = 0.981, AUCPR = 0.971. The Cloud 3D-QSAR server may facilitate the development of good QSAR models in drug discovery. Our server is free and now available at http://chemyang.ccnu.edu.cn/ccb/server/cloud3dQSAR/ and http://agroda.gzu.edu.cn:9999/ccb/server/cloud3dQSAR/.

2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(4): 289-295, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-33167085

RESUMO

OBJECTIVE: To observe the effect of weight control of intermittent fasting in different time course (14 d, 28 d)and explore its effect on skeletal muscle mass and autophagy. METHODS: Sixty SD rats (male) were randomly divided into sedentary group (Sed), intermittent fasting group (InF) and exercise group (Exe), 20 rats of each group, intervention duration is 14 d and 28 d. Animals of InF group were fasted every other day, animals of Exe group underwent aerobic exercise on treadmill, the weight was recorded every week. The body fat mass was recorded by DEXA and then the fat mass index was calculated. The wet weight of bilateral soleus muscle was weighed and wet weight index was calculated. Immunofluorescence was used to detect laminin and light chain 3 (LC3), which reflect muscle fiber cross-sectional area and autophagosome respectively. Transmission electron microscopy was used to observe the number and morphology of autophagosomes. The expression levels of autophagy related proteins Unc-51 like kinase 1 (ULK1), LC3, sequestosome1 protein (p62), AMP activated protein kinase (AMPKα) and p-AMPKα (Thr172) were detected by Western blot. RESULTS: ① From the 7th day of intervention, the body weight of rats in InF and Exe groups was significantly lower than that in Sed group, and the body weight of InF group was significantly lower than that in Exe group (P<0.01). After 28 days of intervention, the fat mass index in InF and Exe groups was significantly lower than that in Sed group, the fat mass index of InF group was significantly lower than that in Exe group (P<0.05).② After 28 days of intervention, the cross-sectional of muscle fibers in Exe group was significantly larger than that in Sed and InF groups (P<0.01). ③The expressions of AMPKα, p-AMPKα (Thr172) and ULK1 in InF and Exe groups were significantly higher than those in Sed group (P<0.05). However, at 14 days, only InF group showed the increase of LC3-II/LC3-I ratio and the decrease of p62 level (P<0.05). The same indicators of Exe group were only significant changed at 28 d. CONCLUSION: ① Intermittent fasting is superior to exercise in controlling the growth of body weight and body fat in rats. ② In terms of skeletal muscle autophagy activation, the length of intervention required for intermittent fasting (14 days) is shorter than aerobic exercise (28 days).

3.
Molecules ; 25(22)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202861

RESUMO

Conductive hydrogel, with electroconductive properties and high water content in a three-dimensional structure is prepared by incorporating conductive polymers, conductive nanoparticles, or other conductive elements, into hydrogel systems through various strategies. Conductive hydrogel has recently attracted extensive attention in the biomedical field. Using different conductivity strategies, conductive hydrogel can have adjustable physical and biochemical properties that suit different biomedical needs. The conductive hydrogel can serve as a scaffold with high swelling and stimulus responsiveness to support cell growth in vitro and to facilitate wound healing, drug delivery and tissue regeneration in vivo. Conductive hydrogel can also be used to detect biomolecules in the form of biosensors. In this review, we summarize the current design strategies of conductive hydrogel developed for applications in the biomedical field as well as the perspective approach for integration with biofabrication technologies.

4.
Int Immunopharmacol ; : 107120, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33162345

RESUMO

OBJECTIVE: To explore the application value of artificial liver support system in the clinical treatment of coronavirus disease 2019 (COVID-19) patients with cytokine storm. METHODS: Six cases of severe or critically severe COVID-19 patients treated in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 22 to February 4, 2020 were recruited, and all of them received artificial liver support treatment. Statistical analysis was carried out on the change of cytokines (TNF-α, IL-10, IL-6, IFN-γ, IL-2, IL-4), inflammation-related indicators (white blood cell, neutrophil, lymphocyte, C-reactive protein and procalcitonin), immune-related indicators (B lymphocyte percentage, natural killer cell percentage, CD3+CD4+CD8 T cell percentage), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 patients before and after treatment, and the proportions of patients with abnormal indicators were analyzed as well. In addition, computed tomography (CT) was used to observe the absorption of pulmonary lesions before and after the artificial liver support treatment. RESULTS: The levels of cytokines (IL-6 and IL-10) were effectively reduced in the 6 patients after treatment with the artificial liver support system. Meanwhile, the proportions of patients with abnormal TNF-α, IL-10, IL-6 and IFN-γ were all decreased (p < 0.05). The levels of inflammation-related indicators including white blood cell, C-reactive protein and procalcitonin, and the proportions of patients with these abnormal indicators were both significantly reduced (p < 0.05). The level of neutrophil was not effectively reduced before and after the treatment, but the proportion was significantly reduced (p < 0.05). However, the abnormality of lymphocyte in the patients was not improved. There was no significant difference in immune-related indicators, AST and ALT before and after the treatment (p > 0.05). CT imaging showed that the artificial liver support treatment contributed to absorption of pulmonary lesions. CONCLUSIONS: The artificial liver support system had a great clinical effect in the treatment of cytokine storm and inflammation in COVID-19 patients, and it could promote the absorption of infected lesions.

5.
J Am Chem Soc ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172264

RESUMO

Flexible metal-organic frameworks (MOFs) hold great promise as smart materials for specific applications such as gas separation. These materials undergo interesting structural changes in response to guest molecules, which is often associated with unique adsorption behavior not possible for rigid MOFs. Understanding the dynamic behavior of flexible MOFs is crucial yet challenging as it involves weak host-guest interactions and subtle structural transformation not only at the atomic/molecular level but also in a nonsteady state. We report here an in-depth study on the adsorbate- and temperature-dependent adsorption in a flexible MOF by crystallizing atomic gases into its pores. Mn(ina)2 shows an interesting temperature-dependent response toward noble gases. Its nonmonotonic, temperature-dependent adsorption profile results in an uptake maximum at a temperature threshold, a phenomenon that is unusual. Full characterization of Xe-loaded MOF structures is performed by in situ single-crystal and synchrotron X-ray diffraction, IR spectroscopy, and molecular modeling. The X-ray diffraction analysis offers a detailed explanation into the dynamic structural transformation and provides a convincing rationalization of the unique adsorption behavior at the molecular scale. The guest and temperature dependence of the structural breathing gives rise to an intriguing reverse of Xe/Kr adsorption selectivity as a function of temperature. The presented work may provide further understanding of the adsorption behavior of noble gases in flexible MOF structures.

6.
Int J Mol Sci ; 21(22)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207795

RESUMO

The Gram-negative bacterium Pseudomonas taiwanensis is a novel bacterium that uses shrimp shell waste as its sole sources of carbon and nitrogen. It is a versatile bacterium with potential for use in biological control, with activities including toxicity toward insects, fungi, and the rice pathogen Xanthomonas oryzae pv.oryzae (Xoo). In this study, the complete 5.08-Mb genome sequence of P. taiwanensis CMS was determined by a combination of NGS/Sanger sequencing and optical mapping. Comparison of optical maps of seven Pseudomonas species showed that P. taiwanensis is most closely related to P. putida KT 2400. We screened a total of 11,646 individual Tn5-transponson tagged strains to identify genes that are involved in the production and regulation of the iron-chelator pyoverdine in P. taiwanensis, which is a key anti-Xoo factor. Our results indicated that the two-component system (TCS) EnvZ/OmpR plays a positive regulatory role in the production of pyoverdine, whereas the sigma factor RpoS functions as a repressor. The knowledge of the molecular basis of the regulation of pyoverdine by P. taiwanensis provided herein will be useful for its development for use in biological control, including as an anti-Xoo agent.

7.
Cell Death Dis ; 11(10): 870, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067426

RESUMO

Recent studies have demonstrated that gastric cancer stem cells (CSCs) are a rare sub-group of gastric cancer (GC) cells and have an important role in promoting the tumor growth and progression of GC. In the present study, we demonstrated that the glycolytic enzyme Enolase 1 (ENO1) was involved in the regulation of the stem cell-like characteristics of GC cells, as compared to the parental cell lines PAMC-82 and SNU16, the expression of ENO1 in spheroids markedly increased. We then observed that ENO1 could enhance stem cell-like characteristics, including self-renewal capacity, cell invasion and migration, chemoresistance, and even the tumorigenicity of GC cells. ENO1 is known as an enzyme that is involved in glycolysis, but our results showed that ENO1 could markedly promote the glycolytic activity of cells. Furthermore, inhibiting glycolysis activity using 2-deoxy-D-glucose treatment significantly reduced the stemness of GC cells. Therefore, ENO1 could improve the stemness of CSCs by enhancing the cells' glycolysis. Subsequently, to further confirm our results, we found that the inhibition of ENO1 using AP-III-a4 (ENOblock) could reduce the stemness of GC cells to a similar extent as the knockdown of ENO1 by shRNA. Finally, increased expression of ENO1 was related to poor prognosis in GC patients. Taken together, our results demonstrated that ENO1 is a significant biomarker associated with the stemness of GC cells.

8.
Polymers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066104

RESUMO

Antibiotic-loaded polymethyl methacrylate (PMMA) has been widely applied in the treatment of knee periprosthetic joint infections. However, problems with antibiotic-loaded PMMA-based spacers, such as structural fracture and implant dislocation, remain unresolved. A novel polyethylene-based spacer, designed with an ultra-congruent articulating surface and multiple fenestrations, was introduced in the current study. Validation tests for biomechanical safety, wear performance, and efficacy of antibiotic cement were reported. During cycle fatigue testing, no tibial spacer failures were observed, and less wear debris generation was reported compared to commercial PMMA-based spacers. The volumetric wear of the novel spacer was within the safety threshold for osteolysis-free volumetric wear. An effective infection control was demonstrated despite the application of lesser antibiotic cement in the 30-day antibiotic elution test. The tube dilution test confirmed adequate inhibitory capabilities against pathogens with the loaded antibiotic option utilized in the current study. The novel polyethylene-based knee spacer may offer sufficient biomechanical safety and serve as an adequate carrier of antibiotic-loaded cement for infection control. Further clinical trials shall be conducted for more comprehensive validation of the novel spacer for practical application.

9.
Sheng Li Xue Bao ; 72(5): 631-642, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33106833

RESUMO

The aim of the present study was to investigate the effects of exercises with different durations and intensities on mitochondrial autophagy and FUNDC1 in rat skeletal muscles. Sixty male Sprague-Dawley rats were randomly divided into 2- and 4-week control groups (Con), moderate-intensity exercise groups (M-ex groups, treadmill exercise, 16 m/min, 1 h/d, 6 d/week), and high-intensity exercise groups (Hi-ex groups, treadmill exercise, 35 m/min, 20 min/d, 6 d/week). The bilateral soleus muscles were separated after the intervention, and paraffin sections were prepared for transmission electron microscopy. ELISA method was used to detect the content of citrate synthase (CS). The co-localizations of microtubule-associated protein 1 light chain 3 (LC3)/cytochrome c oxidase IV (COX-IV), FUNDC1/COX-IV and LC3/FUNDC1 were observed by immunofluorescent staining in frozen sections. The skeletal muscle mitochondria were extracted, and the expression of autophagy-related proteins, including AMPKα, p-AMPKα, Unc-51 like kinase 1 (ULK1), FUNDC1, LC3 and p62, were detected by Western blot. The results showed that exercise increased mitochondrial function, i.e. peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), COX-I protein expression levels and CS content. There was no difference of mitochondrial function parameters between 2-week M-ex and 2-week Hi-ex groups, while mitochondrial function of 4-weeks Hi-ex group was significantly lower than that of 4-week M-ex group. Under the same exercise intensity, mitochondrial autophagy activation in skeletal muscle of 4-week exercise was higher than that in 2-week exercise group; Under the same duration of exercise, mitochondrial autophagy activation of Hi-ex group was higher than that in M-ex group. Both 2- and 4-week exercise intervention increased LC3/COX-IV, COX-IV/FUNDC1, and FUNDC1/LC3 co-localizations. Exercise increased LC3-II/LC3-I ratio, down-regulated p62 protein expression level, up-regulated FUNDC1, ULK1 protein expression levels and AMPKα phosphorylation, and the changes of these proteins in 4-week Hi-ex group were significantly greater than those in 4-week M-ex group. These results suggest exercise induces mitochondrial autophagy in skeletal muscles, and the activity of autophagy is related to the duration and intensity of exercise. The induction mechanism of exercise may involve the mediation of FUNDC1 expression through AMPK-ULK1 pathway.


Assuntos
Autofagia , Mitocôndrias , Animais , Terapia por Exercício , Humanos , Masculino , Proteínas de Membrana/metabolismo , Proteínas de Membrana/fisiologia , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/fisiologia , Músculo Esquelético/metabolismo , Ratos , Ratos Sprague-Dawley
10.
BMC Bioinformatics ; 21(1): 433, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008305

RESUMO

BACKGROUND: Precise disease module is conducive to understanding the molecular mechanism of disease causation and identifying drug targets. However, due to the fragmentization of disease module in incomplete human interactome, how to determine connectivity pattern and detect a complete neighbourhood of disease based on this is still an open question. RESULTS: In this paper, we perform exploratory analysis leading to an important observation that through a few intermediate nodes, most separate connected components formed by disease-associated proteins can be effectively connected and eventually form a complete disease module. And based on the topological properties of these intermediate nodes, we propose a connect separate connected components (C3) method to detect a succinct disease module by introducing a relatively small number of intermediate nodes, which allows us to obtain more pure disease module than other methods. Then we apply C3 across a large corpus of diseases to validate this connectivity pattern of disease module. Furthermore, the connectivity of the perturbed genes in multi-omics data such as The Cancer Genome Atlas also fits this pattern. CONCLUSIONS: C3 tool is not only useful in detecting a clearly-defined connected disease neighbourhood of 299 diseases and cancer with multi-omics data, but also helpful in better understanding the interconnection of phenotypically related genes in different omics data and studying complex pathological processes.


Assuntos
Algoritmos , Doença , Asma/genética , Neoplasias da Mama/genética , Feminino , Ontologia Genética , Humanos , Anotação de Sequência Molecular , Mapas de Interação de Proteínas , Proteínas/metabolismo
11.
Chem Rec ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33021040

RESUMO

Gas sensors based on metal oxides semiconductor (MOS) have attracted extensive attention from both academic and industry. ZnO, as a typical MOS, exhibits potential applications in toxic gas detection, owning to its wide band gap, n-type transport characteristic and excellent electrical performance. Meanwhile, doping is an effective way to improve the sensing performance of ZnO materials. In this review, the effects of different types of doping on morphology, crystal structure, band gap and depletion layer of ZnO materials are comprehensively discussed. Theoretical analysis on the strategies for enhancing the sensing properties of ZnO is also provided. This review puts forward the reasonable insight for designing efficient n-type ZnO-based semiconductor oxide sensing materials.

12.
Acta Otolaryngol ; : 1-4, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32865091

RESUMO

BACKGROUND: The electrical coagulation of sphenopalatine artery(SPA) under nasal endoscopy has gradually become an important surgical intervention for epistaxis. AIM: To investigate the effectiveness and complications of SPA electrocoagulation for epistaxis. MATERIAL AND METHODS: The clinical data of 47 patients undergoing SPA electrocoagulation were analyzed, retrospectively. RESULTS: Forty-seven patients were enrolled, with a male to female ratio of approximately 3:1. 11of 36 were under 45 years old, 25 of 36were 45 years old and above. Among female patients, one was under 45 years old, and the others were 45 years old and above, but there was no significant difference in gender composition between different age groups (χ 2 = 1.069, p = .301). All patients were unilateral epistaxis. The effective control rates of epistaxis within 24 h after surgery, early postoperative, and late postoperative were 100%, 100%, and 97.9%, respectively. There were 6 patients with complications, including 3 patients with nasal dryness and ecdysis on the affected side, 2 patients with numbness on upper lip, 1 patient with nasal adhesion and pus on affected side. CONCLUSION AND SIGNIFICANCE: Refractory epistaxis has no relationship with age and sex, SPA electrcoagulation can effectively control refractory epistaxis and is an effective surgical method.

13.
Mol Genet Genomics ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955620

RESUMO

Spinach (Spinacia olracea L.) is a dioecious leafy vegetable with a highly repetitive genome of around 990 Mb, which is challenging for de-novo genome assembly. In our study, a segregating F1 (double pseudo-testcross) population from 'Viroflay' × 'Cornell-NO. 9' was used for genetic mapping by resequencing genotyping. In the paternal 'Cornell-NO. 9' map, 212,414 SNPs were mapped, and the total linkage distance was 476.83 cM; the maternal 'Viroflay' map included 29,282 SNPs with 401.28 cM total genetic distance. Both paternal and maternal maps have the expected number of six linkage groups (LGs). A non-recombining region with 5678 SNPs (39 bin markers) co-segregates with sex type which located at 45.2 cM of LG1 in the 'Cornell-NO. 9' map while indicates the sex determination region (SDR). Integration of two maps into a consensus map guided us to anchor additional 1242 contigs to six pseudomolecules from the published reference genome, which improved additional 233 Mb (23.4%) assembly based on spinach estimated genome size. Particularly, the X counterpart of SDR in our assembly is estimated around 18.4 Mb which locates at the largest chromosome, as consensus with sex-biased FISH signals from previous cytogenetics studies. The region is featured by reduced gene density, higher percentage of repetitive sequences, and no recombination. Our linkage maps provide the resource for improving spinach genome de-novo assembly and identification of sex-determining genes in spinach.

14.
Zhongguo Gu Shang ; 33(9): 853-9, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32959574

RESUMO

OBJECTIVE: To assess the early clinical effects of oblique lateral lumbar interbody fusion (OLIF) combined with posterior long-segment internal fixation through O-arm CT navigation for the treatment of degenerative scoliosis. METHODS: The clinical data of 15 patients with degenerative scoliosis treated by OLIF combined with posterior long-segment internal fixation through O-arm CT navigation between April 2016 and December were retropectively analyzed. There were 3 males and 12 females, aged from 55 to 73 years old with an average of (62.2±5.3) years. The operation time, intraoperation blood loss, the rate of excellentand good of pedicle screw placement, and complications were recorded. Before surgery, 1 week after surgery and at the final follow-up, the visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the patients' clinical symptoms;standing X-ray film, lumbar spine CT examination was performed at 6 months after surgery to observe coronal scoliosis Cobb angle, lumbar lordosis (LL), intervertebral space height, sagittal vertical axis (SVA), intervertebral fusion, etc. RESULTS: The mean operation time and intraoperative blood loss were respectively (98.7±16.8) min and (50.2±10.7) ml in OLIF surgery, while were (101.5±23.4) min and (63.1±19.7) ml in the surgery of posterior long segment internal fixation. The total mean operation time and intraoperative blood loss were (200.2±40.2) min and (113.3±30.4) ml. All patients were followed from 12 to 25 months with an average of (16.5±5.3) months. Low back pain VAS, lower limb pain VAS and ODI reduced from preoperative (6.8±1.6), (6.2±1.1) scores and (64.6±10.4)% to (1.4±1.0), (1.0±0.5) scores, and (15.8±4.5)% at the final follow-up, the differences were statistically significant(P<0.05). Coronal scoliosis Cobb angle and SVA decreased from preoperative (20.3±13.5)°, (42.3±16.5) mm to (5.5±3.1)°, (25.1±10.9) mm at the final follow-up, and the differences were statistically significant (P<0.05). LL and intervertebral space height increased from preoperative (25.8±8.2)°, (5.9±2.7) mm to (39.3±9.1)°, (10.9±1.2) at the final follow-up, and the differences were statistically significant(P<0.05). Total 240 nails were placed through O-arm CT navigation with the rate of excellent and good of 96%(230/240). Six months after operation, CT of lumbar spine showed interbody fusion of bone. One patient developed anterior medial pain in the left thigh, and two patients experienced transient lefthip flexion after surgery, both of whom recovered during subsequent follow-up. CONCLUSION: The early clinical effect of oblique lateral lumbar interbody fusion combined with posterior long segment internal fixation through O-arm CT navigation is satisfactory in treatment of degenerative scoliosis. It has the advantages of minimal invasion, accurate navigation of nail placement, high bone fusion rate and few complications. It can provide new options for minimally invasive treatment of degenerative scoliosis.


Assuntos
Escoliose , Fusão Vertebral , Cirurgia Assistida por Computador , Idoso , Feminino , Humanos , Imageamento Tridimensional , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
Math Biosci Eng ; 17(4): 2950-2966, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32987509

RESUMO

The polynomial-based image secret sharing (ISS) scheme encodes a secret image into n shadows assigned to n participants. The secret image with high resolution is decoded by Lagrange interpolation when collecting any k or more shadows. Thus, ISS is used in applications such as distributive storage in the cloud, digital watermarking, block chain, and access control. Meaningful shadows are significant in ISS because meaningful shadows decrease the suspicion of image encryption and increase the efficiency of shadow management. Generally, previously meaningful ISS schemes were achieved through embedding the shadows into cover images using information hiding techniques and suffer from large pixel expansion and complex decoding procedure. Digital image processing, such as inpainting (texture synthesis), is a standard technique in multimedia applications. It will be highly significant if ISS can be performed in the processing of a normal digital image processing technique. Generally, the encoding method of an ISS scheme entails the use of a mathematical function that is sensitive to any slight change in the ISS output; therefore, the development of a method for performing the ISS procedure and simultaneously achieving image processing behavior is a key challenge. In this paper, we exploit the behavior ISS (BISS) and realize an image inpainting-based BISS scheme for the (k, n) threshold. Using screening operations, a secret image is encoded into the pixels of cover images by polynomial-based ISS in the processing of inpainting shadows to obtain meaningful shadows similar to the input cover images. In addition, the secret image can be losslessly decoded by Lagrange interpolation when collecting any k or more shadows. Experiments are given to confirm the efficiency of the scheme.

16.
Epilepsy Behav ; 112: 107379, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32920374

RESUMO

OBJECTIVE: Only a few heritable SCN8A variants have been described in patients with a mild phenotype of epilepsy. Here, we describe a Chinese family with a novel inherited SCN8A variant and investigate changes in spontaneous cerebral activity during the resting-state in magnetic resonance imaging (MRI)-negative patients with epilepsy and their unaffected siblings. METHODS: A gene panel targeting 535 epilepsy genes was performed on the proband and his parents. The identified variant was confirmed in other affected members by Sanger sequencing. Resting-state functional MRI (fMRI) data were gathered from the family (4 affected individuals and 3 unaffected siblings) and 72 healthy controls (HCs). Functional connectivity density (FCD) was used to assess whether distant or local functional network changes occurred in patients with epilepsy. RESULTS: A heterozygous missense variant (c.4568C>A; p.A1523D) in SCN8A was identified in the Chinese family, with a total of 7 members who presented with a mild phenotype (childhood seizures and normal cognition). All patients remained seizure-free, and one patient remained seizure-free without medication. Increased FCD values in the thalamocortical network and basal ganglia network were observed in both patients with epilepsy and their unaffected siblings compared with the HCs. Direct comparison between SCN8A variant patients and unaffected siblings showed that more serious and distributed abnormal changes occurred in the mesial frontal regions of patients with epilepsy. CONCLUSIONS: We identified a novel SCN8A variant with a mild familial epilepsy phenotype. A similar pattern of FCD alterations in patients and their unaffected siblings might represent an endophenotype of benign epilepsy associated with the SCN8A inherited variant, and more extensive alterations in mesial frontal regions may help us to further understand the pathogenesis of SCN8A-related mild epilepsy.

17.
Chem Commun (Camb) ; 56(82): 12383-12386, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32931535

RESUMO

An efficient asymmetric allylation reaction of allylboronates with seven-membered cyclic imines, dibenzo[b,f][1,4]oxazepines, is described. The reaction, which is catalyzed by a Bi(OAc)3/CPA system, gives a range of chiral nitrogen-containing heterocycle structures in high yields and with good enantioselectivities. The conversion of these products to nitrogen-containing heterocycles is also demonstrated.

18.
Hum Cell ; 33(4): 1133-1141, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32918700

RESUMO

The long non-coding RNA antisense 1 ADAMTS9-AS1 has been reported to predict the survival in several tumors, including bladder cancer and breast cancer. However, the clinical significance and biological behaviors of ADAMTS9-AS1 in colorectal cancer (CRC) have not been reported yet. In this study, the expression of ADAMTS9-AS1 was measured in CRC tissues and cell lines using quantitative real-time PCR analysis. The clinical significance of ADAMTS9-AS1 was evaluated with Chi-squared test, Kaplan-Meier method and Cox regression analysis in CRC patients. CCK8 assay, colony formation assay, flow cytometry and transwell assay were used to explore the biological function of ADAMTS9-AS1 knockdown in CRC cell lines (SW1116 and HT29). We further explore the role of ADAMTS9-AS1 in vivo though xenograft tumor assay. Our data showed that ADAMTS9-AS1 expression level was significantly up-regulated in CRC tissues and cell lines compared with corresponding controls. High ADAMTS9-AS1 level was associated with TNM stage, lymph node invasion and worse survival prognosis. Depletion of ADAMTS9-AS1 significantly suppressed cell proliferation, G1/S transition, migration and invasion, as well as suppressed CDK4/Cyclin D1 and epithelial-mesenchymal transition (EMT). To sum up, these findings illustrated that ADAMTS9-AS1 might be a promising therapeutic target and prognostic factor for CRC.


Assuntos
Proteína ADAMTS9/genética , Proteína ADAMTS9/metabolismo , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Expressão Gênica , Proteína ADAMTS9/fisiologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/fisiopatologia , Fase G1/genética , Humanos , Metástase Linfática/genética , Terapia de Alvo Molecular , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Prognóstico , Fase S/genética , Regulação para Cima/genética
19.
Zhen Ci Yan Jiu ; 45(9): 720-5, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32959554

RESUMO

OBJECTIVE: To observe the efficacy of electroacupuncture (EA) plus passive stretch exercise in the treatment of disused atrophy of gastrocnemius and soleus muscles in mice. METHODS: Fifty C57BL/6 mice were randomly and equally divided into 5 groups: blank control, model, passive stretch exercise (exercise), EA and EA+exercise groups. The muscular atrophy model was established by fixing the gastrocnemius and soleus muscles with plaster immobilization (by putting the right leg into a plastic vial and then twining the vial with medical plaster bandage from the ankle upwards to the thigh and groin to maintain the knee-joint flexion and ankle joint plantar flexion for 7 days). EA (2 Hz/100 Hz, 1 mA)was applied to bilateral "Zusanli"(ST36) for 10 min, once a day for 4 weeks. For mice with the passive exercise, the plastic vial was removed first, followed by pulling out the hindleg to seize the toes to stretch them until the right hindleg is fully extended, then, pushed the leg towards the body. The procedures were repeated once again and again for 10 min. The exercise was conducted once daily, for 4 weeks. The cross-sectional area of fast and slow muscle fibers of the soleus and gastrocnemius was measured under electronic microscope after ATPase histochemical stain and the expression of slow skeletal muscle troponin (TNNI1) and fast skeletal muscle troponin (TNNI2) in the soleus and gastrocnemius was detected by Western blot. RESULTS: Compared with the blank control group, the cross-sectional areas of the fast and slow muscle fibers of the soleus and gastrocnemius muscles were significantly decreased in the model group (P<0.05, P<0.01). Following the interventions, the cross-sectional areas of the fast and slow muscle fibers of soleus muscle in the EA+exercise group, and those of the fast and slow muscle fibers of the gastrocnemius muscle in the EA and EA+exercise groups, and the expression levels of TNNI1 and TNNI2 proteins in the gastrocnemius muscle of the EA+exercise group were significantly increased in comparison with the model group (P<0.05, P<0.01). CONCLUSION: EA combined with passive stretch exercise can promote the recovery of the soleus and gastrocnemius muscles in disused muscle atrophy mice, which may be related to its effect in up-regulating the expression of TNNI1 and TNNI2 proteins.


Assuntos
Eletroacupuntura , Animais , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético , Atrofia Muscular/genética , Atrofia Muscular/terapia , Ratos Sprague-Dawley , Troponina
20.
World J Gastroenterol ; 26(27): 3929-3937, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32774067

RESUMO

BACKGROUND: Some patients with hepatolithiasis cannot tolerate surgery due to severe cardiac or pulmonary comorbidities, or cannot be endoscopically treated because of altered gastrointestinal anatomies. AIM: To propose a modified percutaneous transhepatic papillary balloon dilation procedure, and evaluate the clinical efficacy and safety of this modality. METHODS: Data from 21 consecutive patients who underwent modified percutaneous transhepatic papillary balloon dilation with hepatolithiasis were retrospectively analyzed. Using auxiliary devices, intrahepatic bile duct stones were pushed into the common bile duct and expelled into the duodenum with an inflated balloon catheter. The outcomes recorded included success rate, procedure time, hospital stay, causes of failure, and procedure-related complications. Patients with possible long-term complications were followed up for 2 years. RESULTS: Intrahepatic bile duct stones were successfully removed in 20 (95.23%) patients. Mean procedure time was 65.8 ± 5.3 min. Mean hospital stay was 10.7 ± 1.5 d. No pancreatitis, gastrointestinal, or biliary duct perforation was observed. All patients were followed up for 2 years, and there was no evidence of reflux cholangitis or calculi recurrence. CONCLUSION: Modified percutaneous transhepatic papillary balloon dilation was feasible and safe with a small number of patients with hepatolithiasis, and may be a treatment option in patients with severe comorbidities or in patients in whom endoscopic procedure was not successful.

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