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1.
Cancer Cell ; 39(2): 225-239.e8, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33357454

RESUMO

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures of arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cysteines within the DNA-binding domain, distal to the zinc-binding site. Arsenic binding stabilizes the DNA-binding loop-sheet-helix motif alongside the overall ß-sandwich fold, endowing p53 mutants with thermostability and transcriptional activity. In cellular and mouse xenograft models, ATO reactivates mutant p53 for tumor suppression. Investigation of the 25 most frequent p53 mutations informs patient stratification for clinical exploration. Our results provide a mechanistic basis for repurposing ATO to target p53 mutations for widely applicable yet personalized cancer therapies.

2.
Eur J Radiol ; 135: 109475, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33373895

RESUMO

PURPOSE: To evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year. MATERIALS AND METHODS: Consecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded. RESULTS: The mean time for US examination was 32 min (range, 20-59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5 %) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95 % CI: 1.652-154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95 % CI: 1.004-1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3 %) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year. CONCLUSIONS: A decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers.

3.
J Ultrasound Med ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270273

RESUMO

OBJECTIVES: Biliary perfusion is considered to contribute to biliary diseases, but routine imaging methods are insufficient to show it. This research investigated the ability of contrast-enhanced ultrasound (CEUS) for biliary perfusion in a biliary ischemia model. METHODS: This research consisted of 2 parts. First, to determine whether CEUS enhancement of the tiny biliary wall represents biliary perfusion, a vascular tracer was used as a reference to evaluate the consistency with the enhancement of the biliary wall on CEUS and the staining by the vascular tracer under the conditions of occluded and recovered biliary perfusion. In the second part, the ability of CEUS for biliary ischemia was further evaluated with microvascular density measurement as a reference. The enhancement patterns were assigned CEUS scores, in which higher scores meant more decreased enhancement, and the diagnostic ability of CEUS was assessed by a receiver operating characteristic curve analysis. RESULTS: The biliary wall was unstained by the vascular tracer and nonenhanced on CEUS when biliary perfusion was interrupted and was stained blue and enhanced after recovery. The biliary wall in the ischemia surgery group showed lower microvascular density measurements (P < .001), decreased enhancement levels (P < .001), and higher CEUS scores (P < .001). When a CEUS score of 3 or higher (obvious decrease of the biliary wall to hypoenhancement or nonenhancement in the arterial phase or rapid wash-out to nonenhancement in the portal venous phase) was applied, CEUS had sensitivity of 87.8%, specificity of 98.3%, accuracy of 93.8%, and an area under the receiver operating characteristic curve of 0.98. CONCLUSIONS: Contrast enhancement of the biliary wall on CEUS represents biliary perfusion and has reasonably good diagnostic performance for biliary ischemia in an experimental animal setting.

4.
Ying Yong Sheng Tai Xue Bao ; 31(11): 3833-3841, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33300734

RESUMO

Quantitative assessment of hydrological connectivity is a hot but difficult issue in current research. Using the 30-m resolution global monthly surface water remote sensing dataset released by the EU Joint Research Center and three indicators of geostatistical connectivity, maximum distance of connection (MDC), and surface water extent of connectome (i.e., seasonally connected water bodies), we quantified the hydrological connectivity of surface water in Momoge National Nature Reserve in different months of a normal year (May to October 2016), and in September of different hydrological years (a wet year, namely 1998; a normal year, namely 2016; a drought year, namely 2002), and different directions (west-east and north-south). Our results showed that: 1) the geostatistical connectivity function (GCF) along the west-east direction was better than that along the north-south direction. The GCF in August and July was better than that in other months. The GCF along the west-east direction of each hydrological year was better than that in the drought year, whereas the GCF in the drought year was better than the corresponding value in the normal year. The GCF along the north-south direction in each hydrological year was better than that in the normal year, whereas the GCF in the normal year was better than that in the drought year. The MDC along the west-east direction in June, July, September, and October of the normal year was all concentrated at 25.26 km. MDC was more concentrated along the north-south direction, with 10 km for all months. The MDC in the normal and drought years was relatively close, but both were much smaller than that in the wet year. 2) frequent seasonal connections between the Yuelianghu Reservoir and the Nenjiang River, and between Etoupao and its neighboring lakes occurred in the study area during the normal year, while most of the other lakes remained isolated. The patterns of hydrological connection in the study area differed across different hydrological years: two giant connectomes were formed in the wet year, some lakes are periodically connected in the normal year, and all lakes remain isolated in the drought year. 3) As a drainage area for farmland receding water, the surface water extent of the Etoupao connectome increased visibly during the three water supplement seasons (spring, summer, and autumn). By quantifying the surface hydrological connectivity in Momoge National Nature Reserve with multiple water sources from different perspectives, our results provide a scientific basis for wetland protection and restoration and integrated management of watershed water resources.

5.
J Cell Mol Med ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215869

RESUMO

LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti-diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6-week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF-α and IL-6 levels. Hepatic transcriptomic analysis showed that the Toll-like receptor signalling pathway was markedly enriched by LLKL treatment. RT-qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut-liver axis, which might contribute to its anti-diabetic effect.

6.
Nanoscale ; 12(38): 19992-20001, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-32996530

RESUMO

The design of Earth-abundant and cost-effective electrocatalysts for highly active and stable electrochemical water splitting in practical production is the primary demand. Herein, bimetallic oxides anchored to three-dimensional (3D) porous conductive nickel foam (NF) are constructed using a simple in situ hydrothermal method for efficient overall water splitting. The vertically aligned Mn3O4/Fe2O3 heterojunction nanosheets have synergy between hierarchical metal oxides and heterogeneous interface, and show excellent performance toward the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in an alkaline environment. By adjusting the molar ratio of Fe : Mn, the morphology, composition and electronic structure of MnFeO-NF-x composites (x represents the ratio of Fe : Mn) can be adjusted to exhibit diverse catalytic activities. In particular, MnFeO-NF-0.4 (0.4 indicates the Fe : Mn ratio of 0.4 : 1) and MnFeO-NF-0.8 display outstanding performance with ultralow overpotentials of 157 mV for the OER and 64 mV for the HER to achieve a current density of 10 mA cm-2, respectively. Furthermore, MnFeO-NF-0.4 and MnFeO-NF-0.8 are assembled into a water splitting electrolyzer, which can reach a current density of 10 mA cm-2 with a low voltage of 1.59 V. Interestingly, Mn-M (M = Co, Ni, and Mo) products can be obtained easily by using different metal salts, indicating the universality of the current one-pot hydrothermal method.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32925000

RESUMO

BACKGROUND: Broad hemodynamic changes, is believed to have a profoundly damaging effect on donor livers after brain death (DBD) or cardiac death (DCD). It remains unclear whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS), the imaging modalities to evaluate perfusion, could provide more information of liver discarded. OBJECTIVE: To evaluate the ability of DUS and CEUS to predict the risk of DBD or DCD liver discarded. METHODS: The consecutive DBD or DCD donors with DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analyzed and the parameters were recorded. RESULTS: Among the 67 eligible donor livers, 15 (22.4%) were discarded and 52 (77.6%) were used. The discarded livers showed prolonged SAT of hepatic artery (0.08s vs 0.06s, OR = 2.169, P = 0.008) on DUS, less cases with homogeneous enhancement (40.0% vs 73.1%, OR = 0.243, P = 0.028) on CEUS, more cases with decreased enhancement (46.7% vs 15.4%, OR = 4.813, P = 0.011), and less difference of the peak time between portal vein and liver parenchymal (0.5s vs 6.7s, OR = 4.260, P = 0.015). The multivariable analysis showed that donor liver with prolonged SAT of hepatic artery (OR = 7.304, 95% CI: 1.195-44.655, P = 0.031) and decreased enhancement (OR = 2.588, 95% CI: 1.234-5.426, P = 0.012) were independent factors of liver discarded. CONCLUSIONS: DUS/CEUS could be applied as a promising predictive tool to screen high-risk liver donors. The prolonged SAT of hepatic artery on DUS and the decrease of liver donor in enhancement on CEUS, indicating hemodynamic changes in DBD and DCD donor livers, were risk factors of liver discarded.

8.
Chem Commun (Camb) ; 56(82): 12339-12342, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32930292

RESUMO

Herein, we have synthesized successfully a three-dimensional/two dimensional (3D/2D) core-shell Cu2O@Fe-Ni3S2 nanoflower on copper foam at room temperature. Remarkably, by virtue of rich active sites and vacancies, large surface area, high conductivity and close contact with the electrolyte, the Cu2O@Fe-Ni3S2 catalyst exhibits superior stability and oxygen evolution reaction performance.

9.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1816-1823, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489065

RESUMO

The aim of this paper was to predict the multi-compound, multi-target and multi-pathway mechanism of Guilu Erxianjiao in treating post-traumatic stress disorder(PTSD) based on network pharmacology. Active compounds and corresponding targets of Guilu Erxianjiao were obtained from TCMSP, BATMAN-TCM, Chemistry and DrugBank database, and known therapeutic targets of PTSD were obtained from OMIM, TTD and DisGeNET Database. The protein interaction network of compound-disease was then built by combining with the STRING Database. Topological parameters of the network were analyzed by Cytoscape 3.6.0 to get key active compounds and their targets. The GO biological process analysis and KEGG pathway analysis of the key targets were conducted. Based on the results of KEGG, the "compound-target-pathway" network was built by Cytoscape 3.6.0 and the results were verified by SystemsDock online molecular docking tool. The prediction results showed that there were 67 active compounds and 420 targets for Guilu Erxianjiao, and 206 known PTSD-related therapeutic targets. Besides, 66 targets, 58 terms and 22 pathways were obtained from Cytoscape 3.6.0 topological parameters analysis, GO biological process analysis, and KEGG pathway analysis, respectively. Molecular docking results showed that both target with the maximum degree value and common targets of PTSD and Guilu Erxianjiao in the pathway can be effectively combined with their corresponding active compounds through molecular docking. The results suggested that Guilu Erxianjiao could exert anti-PTSD effect by regulating synaptic plasticity, anti-apoptotic, anti-inflammatory and promoting fear memory extinction through pathways such as LTP, PI3 K/Akt/mTOR, TNF, serotonergic synapse and dopaminergic synapse. This study provides a theoretical basis for further elucidating pharmacological mechanisms of Guilu Erxianjiao in treating PTSD.


Assuntos
Medicamentos de Ervas Chinesas , Transtornos de Estresse Pós-Traumáticos , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas
10.
Nat Commun ; 11(1): 2349, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376828

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

11.
Nat Commun ; 11(1): 1865, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313027

RESUMO

Bacterial Rhs proteins containing toxic domains are often secreted by type VI secretion systems (T6SSs) through unclear mechanisms. Here, we show that the T6SS Rhs-family effector TseI of Aeromonas dhakensis is subject to self-cleavage at both the N- and the C-terminus, releasing the middle Rhs core and two VgrG-interacting domains (which we name VIRN and VIRC). VIRC is an endonuclease, and the immunity protein TsiI protects against VIRC toxicity through direct interaction. Proteolytic release of VIRC and VIRN is mediated, respectively, by an internal aspartic protease activity and by two conserved glutamic residues in the Rhs core. Mutations abolishing self-cleavage do not block secretion, but reduce TseI toxicity. Deletion of VIRN or the Rhs core abolishes secretion. TseI homologs from Pseudomonas syringae, P. aeruginosa, and Vibrio parahaemolyticus are also self-cleaved. VIRN and VIRC interact with protein VgrG1, while the Rhs core interacts with protein TecI. We propose that VIRN and the Rhs core act as T6SS intramolecular chaperones to facilitate toxin secretion and function.


Assuntos
Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/metabolismo , Toxinas Bacterianas/metabolismo , Chaperonas Moleculares/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Aeromonas/metabolismo , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Genes Bacterianos , Mutação , Óperon , Peptídeo Hidrolases , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo
12.
Anticancer Drugs ; 31(9): 908-917, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32097138

RESUMO

Hepatocellular carcinoma is the second leading cause of cancer-related death worldwide. Neural regulation plays an important role in the development of hepatocellular carcinoma, and activation of sympathetic nervous system can promote the migration and invasion of cancer cells. However, little research has been conducted on how the vagus nerve influences hepatocellular carcinoma. In this study, we found that the expression of vesicular acetylcholine transporter, a biomarker of vagus nerve, was associated with hepatocellular carcinoma patients' clinicopathological characteristics by immunohistochemistry. Further, activation of muscarinic acetylcholine receptor 1 (M1R) promoted HepG2 and SMMC-7721 cells migration and invasion and epithelial-mesenchymal transition via PI3K/Akt pathway. Moreover, inhibition of M1R by antagonist or shRNA suppressed hepatocellular carcinoma cells migration and invasion in vitro and in vivo, inhibited epithelial-mesenchymal transition and PI3K/Akt pathway. Therefore, these results indicate that activation of M1R promotes invasion of hepatocellular carcinoma through epithelial-mesenchymal transition and PI3K/Akt pathway.

13.
Int J Clin Exp Pathol ; 13(1): 21-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32055268

RESUMO

Lymphadenopathy is an important characteristic of POEMS syndrome, and a Castleman disease (CD)-like pathologic change in the lymph nodes is one of the major diagnostic criteria. However, the characteristics of lymphadenopathy in POEMS still have not been completely elucidated. The lymph node biopsies are available only for a small proportion of patients. A simple and safe way is needed to rule CD in or out. This study aimed to analyse the features of lymphadenopathy and estimate the role of imaging methods, including computed tomography (CT) and positron emission tomography-CT (PET/CT), in the diagnosis of lymphadenopathy in patients with POEMS syndrome. We conducted a retrospective analysis of 23 patients with confirmed POEMS syndrome. All of the patients received chest and abdominal CT scan and/or superficial ultrasound examinations. Four patients underwent PET/CT examinations, and 6 patients received lymph node biopsies. Enlarged lymph nodes (short diameter ≥ 1 cm) were found in 48% (11/23) of patients, but only 1 patient had an enlarged lymph node with a diameter ≥ 2 cm. Lymph nodes with CD-like pathologic changes from 2 patients showed increased maximum standard uptake values (SUVmax) of 18F-deoxyglucose (18FDG) on PET/CT, while lymph nodes with reactive pathologic changes from 2 other patients showed a normal metabolic PET/CT profile. The extent of lymph node enlargement in patients with POEMS was less than that in patients with CD per se. We draw the conclusion that most of the enlarged lymph nodes had diameters ≤ 2 cm, which is less than that in cases of CD per se and PET/CT may be helpful in determining whether enlarged lymph nodes are characterized by CD-like changes or not.

14.
Recent Pat Nanotechnol ; 14(1): 21-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31368882

RESUMO

BACKGROUND AND OBJECTIVE: Some patents have reported the centrifugal spinning method which utilizes the centrifugal force produced by a high speed rotating device to fabricate fibers from polymer melts or solutions. Recently, with the development of technologies, centrifugal spinning was employed to produce ultrafine fibers and nanofibers. In order to improve the equipment and technology of centrifugal spinning and obtain finer fibers, it is important to model the polymer drawing of the centrifugal spinning. METHODS: The polymer drawing in the centrifugal spinning is modeled and simulated. The force balance equation and heat transfer balance equation are established after analyzing the motion and heat transfer of the polymer melts. These nonlinear equations are solved based on the least square method to obtain the radius of excircle and the shape of streamline. A fourth order Runge-Kutta method is utilized to obtain the diameter and temperature of the threadline because there are initial value problems of first order ordinary differential equations. Streamlines and diameter of polymer melts at different viscoelasticities and different spinning temperatures are obtained. The simulation results are compared with the measured results to verify the polymer drawing model. RESULTS: The viscoelastic force in the centrifugal spinning changes constantly at a fixed rotation speed of the rotating spinneret. As the spinneret is rotating, the radius of excircle R1 increases slowly when the time passes, which means the viscoelastic force decreases slowly. The change of the viscoelastic force accelerates the increase of the radius vector. The simulation results show that the threadline diameter under the condition of changing viscoelastic forces is smaller than that under the condition of fixed visoelastic forces. The temperature of the polymer melts decreases faster under the condition of changing viscoelastic forces than that under the condition of fixed visoelastic forces. The threadline diameter decreases with the increase of the rotation speed. Higher initial polymer temperatures yield smaller fiber diameters. CONCLUSION: The polymer drawing in the centrifugal spinning is modeled and simulated. The simulation results tally with the measured results confirming the effectiveness of the polymer drawing model. The simulation results show that the change of the viscoelastic force is favorable to the polymer drawing and both larger rotation speeds and higher initial polymer temperatures can produce finer fibers, which lays a good foundation for the computer-assisted design of the centrifugal spinning.

15.
Eur J Gastroenterol Hepatol ; 32(1): 120-126, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31688313

RESUMO

OBJECTIVES: In longitudinal studies, serum biomarkers are often measured longitudinally which is valuable to predict the risk of disease progression. Previous risk prediction models for liver cirrhosis restrict data to baseline or baseline and a single follow-up time point, which failed to incorporate the time-dependent marker information. The aim of this study is to develop risk model in patients with chronic hepatitis B for dynamic prediction of cirrhosis by incorporating longitudinal clinical data. METHODS: Data from the hospital-based retrospective cohort at the Third Affiliated Hospital of Sun Yat-sen University, from 2004 to 2016, were analyzed. Using the multilevel logistic regression model, the time-dependent marker information and individual characteristics were taken as input, and the risk of at different time as the output. RESULTS: At the end of follow-up, 8.8% of patients progressed to cirrhosis, the average estimate values of hepatitis B virus DNA and alanine aminotransferase demonstrated a downward trend, the aspartate aminotransferase/alanine aminotransferase ratio showed a flat trend overall. The important predictors were as follows: age, oral antiviral treatment, hepatitis B virus DNA. This risk prediction model had an area under the receiver operator characteristic curve of 0.835 (95% confidence interval: 0.772-0.899) and 0.809 (95% confidence interval: 0.708-0.910) in the derivation and validation sets, respectively. CONCLUSION: Longitudinal prediction model can be used for dynamic prediction of disease progression and identify changing high-risk patients.

16.
Breast Cancer ; 27(1): 147-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31410735

RESUMO

OBJECTIVE: The miR-638 acted as a tumor suppressor and E2F transcription factor 2 (E2F2) was a critical regulator in some cancers, while the role of them on stemness of breast cancer stem cells (BCSCs) was rarely detailed. Hence, we focused on exploring the effects of miR-638 and E2F2 on BCSCs stemness. METHODS: The proportion of CD24 -/CD44 + cells of BCSCs was detected by flow cytometry. The target relationship of miR-638 and E2F2 was explored using luciferase assays. The ability of self-renewal, proliferation, and invasion of BCSCs were determined by Mammosphere forming, Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. Xenograft tumor was established to detect the influence of miR-638 on tumor growth. RESULTS: miR-638 was down-regulated, while E2F2 was elevated in breast cancer. The E2F2 level was negatively correlated with miR-638. The BCSCs represented higher proportion of CD24 -/CD44 + cells and levels of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4). The miR-638 was down-regulated and E2F2 was increased in BCSCs. MiR-638 could target to E2F2 and decreased the level of E2F2 in BCSCs cells. Overexpression of miR-638 decreased the proportion of CD24 -/CD44 + cells and the levels of SOX2 and OCT4 by inhibiting E2F2. The overexpression of miR-638 also inhibited the abilities of self-renewal, proliferation, and invasion of BCSCs by inhibiting E2F2. The miR-638 overexpression inhibited the breast tumor growth. CONCLUSION: MiR-638 represses the characteristics and behaviors of BCSCs by targeting E2F2. MiR-638 may be a potential target for breast cancer therapy.


Assuntos
Neoplasias da Mama/genética , Fator de Transcrição E2F2/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Animais , Sítios de Ligação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Autorrenovação Celular , Fator de Transcrição E2F2/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Células MCF-7 , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , RNA Interferente Pequeno
17.
Neural Regen Res ; 15(6): 1150-1159, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31823896

RESUMO

The depression-like behavior phenotype, neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy. The present study aimed to clarify the dynamic changes of depression-like behavior, dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment. Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors, including white noise, thermal swimming, stroboscopic illumination, soiled cages, pairing with three other stressed animals, cold swimming, tail pinch, restraint and water and food deprivation. Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group (normal feeding without any stressors). To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression, a sucrose preference test was used to evaluate the degree of anhedonia. An open-field test was used to evaluate locomotor activity and anxiety status. Compared with the control group, chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks. Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks. In addition, chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling. To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression, markers (DCX and DCX/BrdU) of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence. Compared with the control group, neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks; however, neural proliferation and differentiation in the dentate gyrus decreased, and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group. Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression. The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group. These findings indicate that during chronic unpredictable mild stress-induced depression, the behavioral phenotype, miR-124 expression in the hippocampus, neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes, which suggested that various pathological changes occur at different stages of depression. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.

18.
Recent Pat Nanotechnol ; 13(3): 189-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613734

RESUMO

BACKGROUND AND OBJECTIVE: The air-flow field of the air centrifugal spinning is simulated and measured. The simulated air velocities coincide well with the measured ones, confirming the correctness of the air-flow field model. METHODS: The polymer drawing in the air-flow field of the air centrifugal spinning is modeled and simulated. Effects of the rotation speed and initial air velocity on the diameter and radius vector of the threadline are investigated. RESULTS: The air velocity is found to decrease with the increase of the distance away from the nozzle exit. Simulation results show that both larger rotation speed and higher initial air velocity can reduce the threadline diameter. CONCLUSION: The radius vector of the threadline increases rapidly with the increase of the initial air velocity, which is helpful to reduce the threadline diameter.

19.
J Cell Commun Signal ; 13(1): 99-112, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30030687

RESUMO

Recent studies have shown that long non-coding RNAs (lncRNAs) play a pivotal role in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the biological action and potential mechanism of liver cancer cell drug resistance have not been clearly clarified. In this study, lncRNAs were screened and differentially expressed in parental and cisplatin-resistant cell lines (HepG2 and HepG2/CDDP). A novel lncRNA, termed NRAL (Nrf2 regulation-associated lncRNA), was identified, and the initial results indicated that it was highly expressed in HepG2 cisplatin resistant cell lines compared to their parental counterparts. Functionally, NRAL depletion significantly enhanced CDDP-mediated cytotoxicity and apoptosis in two cisplatin-resistant HCC cell lines. Mechanistically, the results indicated that NRAL regulates Nrf2 expression through miR-340-5p serving as a competing endogenous RNA (ceRNA), thus influencing the CDDP-induced phenotype in HCC. Collectively, the present investigation suggest that the NRAL/miR-340-5p/Nrf2 axis mediates cisplatin resistance in HCC, which may provide novel targets for overcoming cisplatin resistance in hepatocellular carcinoma cells.

20.
Can J Gastroenterol Hepatol ; 2018: 1020925, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402448

RESUMO

T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Hepatite B Crônica/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptores CCR7/imunologia , Receptores CXCR5/imunologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Citometria de Fluxo , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Imunidade Ativa/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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