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1.
J Ultrasound Med ; 43(7): 1333-1342, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38563453

RESUMO

OBJECTIVES: Ultrasound-targeted microbubble disruption (UTMD) is a widely used technique to improve the differentiation and proliferation capacity of mesenchymal stem cells (MSCs), but the optimal therapeutic parameters for UTMD are unclear. In this study, we aimed to find the appropriate peak negative pressure (PNP), which is a key parameter for enhancing the stemness properties and proliferation of MSCs. METHODS: Experiments were performed in UTMD group, ultrasound (US) group under different PNP exposure conditions (0.5, 1.0, and 1.5 MPa), and control group. Apoptosis safety was analyzed by flow cytometry and MSC proliferation was measured at 12, 24, and 36 hours after irradiation by cell counting kit 8. The expression of the stemness genes NANOG, OCT-4, and SOX-2 were determined by enzyme-linked immunosorbent assay (ELISA) or reverse transcription polymerase chain reaction. RESULTS: The results showed that the 1.5 MPa UTMD-treated group had the highest proliferation capacity of MSCs at 24 hours. ELISA or quantitative reverse transcription polymerase chain reaction results showed that UTMD treatment of the 1.5 MPa group significantly upregulated the expression of the stemness genes NANOG, SOX-2, and OCT-4. CONCLUSIONS: In conclusion, the appropriate peak PNP value of UTMD was 1.5 MPa, and 1.5 MPa-mediated UTMD group obviously promoted MSCs proliferation and maintained stemness by upregulating the expression of stemness genes.


Assuntos
Proliferação de Células , Células-Tronco Mesenquimais , Microbolhas , Regulação para Cima , Células Cultivadas , Ondas Ultrassônicas , Animais , Células da Medula Óssea
2.
J Clin Ultrasound ; 52(3): 331-337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38126255

RESUMO

Malignant triton tumor (MTT) is a highly aggressive malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. There are few reports that MTT occurred in urogenital system. In the present study, we report the first MTT occurring in the uterus. A 57-year-old woman came to the emergency department due to persistent vaginal bleeding for 2 months. The gynecological palpation found that a club-shaped excrescence existed in the vagina about 7 cm × 3 cm × 3 cm. The mass located in the lower segment of the uterus and the cervix was confirmed by gynecological vaginal ultrasound and magnetic resonance imaging, which was preliminarily diagnosed as cervical carcinoma. After neoplasm punch biopsy, the pathological diagnosis was malignant triton tumor. The patient finally lost follow-up. This is the first report about MTT in the uterus and suggests that pathological biopsy combined with imaging examination is necessary for the diagnosis of rarely MTT.


Assuntos
Neoplasias de Bainha Neural , Neurilemoma , Neurofibrossarcoma , Neoplasias Cutâneas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Bainha Neural/patologia , Útero/diagnóstico por imagem , Útero/patologia
3.
Inorg Chem ; 62(4): 1602-1610, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36661296

RESUMO

Two-dimensional (2D) layered MoSe2 has been demonstrated to be a promising electrode material for new energy storage systems. However, its nature of poor conductivity and the undesirable interlayer spacing hinder its further application. In this paper, a general and simple plasma-enhanced chemical vapor deposition method is proposed to produce 2D heterolayer-structured MoSe2-carbon (MoSe2/C) with carbon atoms inserted in the MoSe2 layers. After morphology optimization, when applying flat-type MoSe2/C-200 nanosheets with an enlarged interlayer spacing of 0.79 nm as the anode and activated carbon as the cathode, the assembled sodium-ion hybrid capacitors can reach a maximum energy/power density of 116.5 W h kg-1/107.5 W kg-1 and exhibit superior cycling durability (91.3% capacitance retention after 4000 cycles at 1 A g-1). The good electrochemical property can be ascribed to the enlarged interlayer spacing that can offer fast diffusion channels for Na ions, and the carbon layer sandwiched in the MoSe2 layer can not only enhance the electron transfer, accelerating the reaction kinetics, but also alleviate the volume change of MoSe2, ensuring the good stability of the electrode. The proposed approach can also be extended to other 2D transition metal chalcogenide (TMC) materials for constructing the TMC/C heterostructures for the application in energy storage systems.

4.
Exp Cell Res ; 417(2): 113248, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35690133

RESUMO

Scarring is the primary factor of maxilla growth restriction among people who have undergone cleft palate repair surgery. p38 mitogen-activated protein kinase (p38MAPK) promotes fibrosis in a variety of organs. However, its role in post-surgery scarring on the hard palate has not been fully understood. This study is designed to investigate the role of p38MAPK in scar formation and maxilla growth of rats. We removed the mucosa on the hard palate of rats and applied the p38MAPK silencing adenovirus vector on it two weeks after surgery. Then the scarring tissue and maxilla growth were evaluated by histological and morphological examination. The effect of p38MAPK silencing on scarring-related genes in fibroblasts was also studied. We found that local injection of Ad-p38MAPK-1 in vivo effectively reduces the expression of p38MAPK and scarring-related proteins and weakens the impact of scarring on the width of the hard palate. Mechanistically, p38MAPK silencing inhibits the expression of α-smooth muscle actin (α-SMA) via mediating the production and nuclear localization of myocardin-related transcription factor A (MRTF-A) in fibroblasts. These results reveal a molecular pathway of scar formation involving p38MAPK/MRTF-A stimulation and support targeting p38MAPK as a potentially effective treatment for post-surgery scarring on the hard palate.


Assuntos
Fissura Palatina , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Proliferação de Células , Células Cultivadas , Cicatriz , Fissura Palatina/genética , Fissura Palatina/cirurgia , Humanos , Proteínas Nucleares , Ratos , Transativadores , Fatores de Transcrição/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
BMC Surg ; 23(1): 211, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496026

RESUMO

BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.


Assuntos
Gangrena de Fournier , Tratamento de Ferimentos com Pressão Negativa , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Gangrena de Fournier/cirurgia , Estudos Retrospectivos , Desbridamento/métodos , Drenagem
6.
Sensors (Basel) ; 23(12)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37420913

RESUMO

Optical neural networks can effectively address hardware constraints and parallel computing efficiency issues inherent in electronic neural networks. However, the inability to implement convolutional neural networks at the all-optical level remains a hurdle. In this work, we propose an optical diffractive convolutional neural network (ODCNN) that is capable of performing image processing tasks in computer vision at the speed of light. We explore the application of the 4f system and the diffractive deep neural network (D2NN) in neural networks. ODCNN is then simulated by combining the 4f system as an optical convolutional layer and the diffractive networks. We also examine the potential impact of nonlinear optical materials on this network. Numerical simulation results show that the addition of convolutional layers and nonlinear functions improves the classification accuracy of the network. We believe that the proposed ODCNN model can be the basic architecture for building optical convolutional networks.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Simulação por Computador
7.
Mol Cancer ; 21(1): 37, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130920

RESUMO

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.


Assuntos
Antineoplásicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma de Células de Transição/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
8.
Ecotoxicol Environ Saf ; 242: 113878, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849902

RESUMO

Nickel-induced allergic contact dermatitis (ACD) is a common skin disease. The mechanism by which nickel causes ACD is not clear. There is no treatment for it, only symptomatic therapy. However, due to the lifetime sensitization characteristics, the recurrence rate in patients is high. T lymphocytes play a key role in nickel-induced ACD. Elucidating the potential mechanism underlying nickel-induced T lymphocyte signalling might make it possible to achieve targeted treatment of nickel-induced ACD. In our study, a phosphoproteomic approach based on tandem mass tag (TMT) labelling and LCMS/MS analyses was employed. An animal model of nickel allergy was established. Splenic T lymphocytes were purified for quantitative phosphoproteomic analysis. The numbers of phosphoproteins, phosphopeptides and phosphosites identified in this study were 3072, 7977 and 10,200, respectively. Comprehensive gene ontology (GO) analysis combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that nickel can significantly affect the phosphorylation of the mTOR signalling pathway in T lymphocytes. Western blotting analysis was used to detect changes in the expression of autophagy-related proteins (Beclin 1, LC3II, and p62). Nickel allergy changed autophagy-related protein expression (p < 0.05). It has been demonstrated that nickel causes autophagy of T lymphocytes in the spleen. Using autophagy inhibitors to intervene, it was found that Th1 differentiation was inhibited, and the expression of Th1-related inflammatory factors was downregulated. Overall, the identification of relevant signalling pathways yielded new insights into the molecular mechanisms underlying nickel allergy and might help in the discovery and development of mechanism-based drugs.


Assuntos
Dermatite Alérgica de Contato , Níquel , Animais , Autofagia , Níquel/toxicidade , Transdução de Sinais , Linfócitos T
9.
BMC Med Educ ; 21(1): 532, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649532

RESUMO

BACKGROUND: Vertigo and dizziness (VD) are among the most frequently seen symptoms in clinics and are important for medical students, especially for those in Chinese standardized residency training (SRT). The aim of our study was to examine the PAL method's feasibility in the clinical teaching of VD-related diseases for SRT students in China. METHODS: This is a randomized, controlled, multicenter study. A total of 228 residents were invited to participate in this study, of which 198 completed the program. The students were randomized into two groups, and VD-related diseases were taught using lecture-based learning (control group) or peer-assisted learning (PAL). An examination paper and a rating scale were used to evaluate students' performance in the mastery of VD-related theoretical knowledge and clinical skills, meanwhile students' perceptions, satisfaction, and risk of burnout were also analyzed using a questionnaire. Independent-samples t-test and chi-square analysis were performed to evaluate statistical significance for continuous variables and categorical variables, respectively, using SPSS 18.0 software. RESULTS: The PAL group performed better in mastering theoretical knowledge and clinical skills than the control group. And more students believed that PAL could help improve their personal qualities such as teamwork skills. However, more students reported that PAL increased the risk of burnout. CONCLUSIONS: PAL was a suitable and effective method in the clinical teaching of some specialized diseases, especially it was recommended for students who had gained initial knowledge and skills, such as Chinese SRT students. However, we should draw attention to the increased risk of burnout if PAL is intended to be widely used in clinical teaching. TRIAL REGISTRATION: ISRCTN registry, ISRCTN53773239 , 05/07/2021, retrospectively registered.


Assuntos
Educação de Graduação em Medicina , Internato e Residência , Estudantes de Medicina , China , Tontura , Humanos , Grupo Associado , Ensino , Vertigem/diagnóstico
10.
Cell Biochem Funct ; 38(5): 630-641, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32390230

RESUMO

Glioblastoma is one of the most malignant tumors and causes the high mortality in cancer patients. Currently, there is no highly efficient therapy against glioblastoma. Therefore, searching for a new molecular target to anti-glioblastoma therapy is urgent and necessary. In this study, we elucidated the role of Signal transducer and activator of transcription 1 (STAT1) in proliferation, migration and apoptosis of glioblastoma cells. We found that STAT1 downregulation could weaken the aggressiveness of glioblastoma cells. Besides, the glioblastoma growth in vivo was also inhibited with the STAT1 downregulation by shRNA as well as by pharmacological stimulation withSTAT1inhibitors. This negative regulation of tumor growth was accompanied by the inhibition in epithelial-mesenchymal transition (EMT), whereas the STAT1 overexpression promoted EMT. Furthermore, the involvement of wnt/ß-catenin was observed in STAT1 downregulation mediated weakness in glioblastoma aggressiveness since application of activator wnt agonist 1 could counteract the inhibitory effect induced by STAT1 downregulation. Collectively, this work provided the evidence to support the conclusion that STAT1 can regulate the glioblastoma growth and migration, potentially serving as a therapeutic target against glioblastoma. SIGNIFICANCE OF THE STUDY: Glioblastoma is one of the most malignant tumors with very high mortality. Until now, there is no efficient therapy against glioblastoma. In this study, we found downregulation of Signal transducer and activator of transcription 1 (STAT1) could weaken the aggressiveness of glioblastoma cells through inhibition in epithelial-mesenchymal transition, mediated through wnt/ß-catenin signalling pathway. Thus, this work supported the regulatory role of STAT1 in glioblastoma growth and migration. This potentially serves as a new therapeutic target against glioblastoma.


Assuntos
Neoplasias do Sistema Nervoso Central/metabolismo , Glioblastoma/metabolismo , Fator de Transcrição STAT1/metabolismo , Animais , Sobrevivência Celular , Neoplasias do Sistema Nervoso Central/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT1/genética , Células Tumorais Cultivadas , Via de Sinalização Wnt
11.
Small ; 15(25): e1900107, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066210

RESUMO

Two-dimensional (2D) materials have attracted extensive research interest in academia due to their excellent electrochemical properties and broad application prospects. Among them, 2D transition metal carbides (Ti3 C2 Tx ) show semiconductor characteristics and are studied widely. However, there are few academic reports on the use of 2D MXene materials as memristors. In this work, reported is a memristor based on MXene Ti3 C2 Tx flakes. After electroforming, Al/Ti3 C2 Tx /Pt devices exhibit repeatable resistive switching (RS) behavior. More interestingly, the resistance of this device can be continuously modulated under the pulse sequence with 10 ns pulse width, and the pulse width of 10 ns is much lower than that in other reported work. Moreover, on the nanosecond scale, the transition from short-term plasticity to long-term plasticity is achieved. These two properties indicate that this device is favorable for ultrafast biological synapse applications and high-efficiency training of neural networks. Through the exploration of the microstructure, Ti vacancies and partial oxidation are proposed as the origins of the physical mechanism of RS behavior. This work reveals that 2D MXene Ti3 C2 Tx flakes have excellent potential for use in memristor devices, which may open the door for more functions and applications.

12.
Small ; 15(24): e1901423, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31045332

RESUMO

Memristors with nonvolatile memory characteristics have been expected to open a new era for neuromorphic computing and digital logic. However, existing memristor devices based on oxygen vacancy or metal-ion conductive filament mechanisms generally have large operating currents, which are difficult to meet low-power consumption requirements. Therefore, it is very necessary to develop new materials to realize memristor devices that are different from the mechanisms of oxygen vacancy or metal-ion conductive filaments to realize low-power operation. Herein, high-performance and low-power consumption memristors based on 2D WS2 with 2H phase are demonstrated, which show fast ON (OFF) switching times of 13 ns (14 ns), low program current of 1 µA in the ON state, and SET (RESET) energy reaching the level of femtojoules. Moreover, the memristor can mimic basic biological synaptic functions. Importantly, it is proposed that the generation of sulfur and tungsten vacancies and electron hopping between vacancies are dominantly responsible for the resistance switching performance. Density functional theory calculations show that the defect states formed by sulfur and tungsten vacancies are at deep levels, which prevent charge leakage and facilitate the realization of low-power consumption for neuromorphic computing application.

13.
BMC Neurol ; 19(1): 85, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053106

RESUMO

BACKGROUND: Wilson's disease (WD) is an autosomal recessive disease of impaired copper metabolism. Previous study demonstrated that WD with corpus callosum abnormalities (WD-CCA) was limited to the posterior part (splenium). This study aimed to compare clinical features between WD-CCA and WD without corpus callosum abnormalities (WD-no-CCA). METHODS: Forty-one WD patients who had markedly neurological dysfunctions were included in this study. We retrospectively reviewed clinical, biochemical characteristics and MRI findings in the 41 WD patients. All patients were assessed using the Unified Wilson's Disease Rating Scale. RESULTS: Nine patients had corpus callosum abnormalities, 4 of 9 patients had abnormal signal in the genu and splenium, 5 of 9 patients had abnormal signal only in the splenium. WD-CCA had longer course (9.9 ± 4.0 years vs. 3.4 ± 3.6 years, p<0.01), more severe neurological dysfunctions (37.6 vs. 65.9, p<0.01) and higher psychiatric symptoms scores (11.2 vs. 22.5, p<0.01) than WD-no-CCA. The MRI findings indicated that WD-CCA had higher ratio than WD-no-CCA in globus pallidus (88.9% vs. 43.8%, p = 0.024) and thalamus (100% vs. 59.4%, p = 0.038). The index of liver function and copper metabolism had no significant in WD-CCA and WD-no-CCA patients. CONCLUSION: Our findings indicate Wilson's disease can involve the posterior as well as the anterior part of CC and patients with CC involvement had more extensive brain lesions, more severe neurological dysfunctions and psychiatric symptoms.


Assuntos
Corpo Caloso/patologia , Degeneração Hepatolenticular/patologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos
14.
Environ Sci Technol ; 53(12): 6927-6936, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31117534

RESUMO

Promotion of iron solubility using ligands is the preliminary step in the homogeneous electro-Fenton (EF) process at a mild pH, but the chelate efficiencies of most organic ligands are unsatisfactory, resulting in insufficient Fe(II) availability. In this study, atomic H* was, for the first time, introduced to the EF process to accelerate the regeneration of the Fe(II)-complex at a mild pH using a Ni-deposited carbon felt (Ni-CF) cathode. The introduction of atomic H* significantly elevated total organic carbon (TOC) abatement of ciprofloxacin (CIP) from 42% (CF) to 81% (Ni-CF) at a natural pH. In the presence of humic acids (HAs), atomic H* introduced via Ni-CF enhanced the CIP degradation rate to 10 times that of the CF at a mild pH. The electron spin resonance (ESR), density functional theory (DFT) calculations, electrochemical characterization, and in situ electrochemical Raman study clearly demonstrated that the atomic H* generated from the Ni-CF cathode was highly efficient at reducing Fe(III)-complexes at a natural pH. Additionally, the Ni-CF could generate atomic H* without significant nickel leaching. Thus, the atomic H* could continuously facilitate iron cycling and, consequently, enhance pollutant mineralization via the homogeneous EF process at a mild pH in an environmentally friendly manner.


Assuntos
Compostos Ferrosos , Poluentes Químicos da Água , Eletrodos , Compostos Férricos , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Oxirredução
15.
Sensors (Basel) ; 19(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174379

RESUMO

Fused filament fabrication (FFF) is one of the most widely used additive manufacturing (AM) technologies and it has great potential in fabricating prototypes with complex geometry. For high quality manufacturing, monitoring the products in real time is as important as maintaining the FFF machine in the normal state. This paper introduces an approach that is based on the vibration sensors and data-driven methods for in-situ monitoring and diagnosing the FFF process. The least squares support vector machine (LS-SVM) algorithm has been applied for identifying the normal and filament jam states of the FFF machine, besides fault diagnosis in real time. The identification accuracy for the case studies explored here using LS-SVM is greater than 90%. Furthermore, to ensure the product quality during the FFF process, the back-propagation neural network (BPNN) algorithm has been used to monitor and diagnose the quality defects, as well as the warpage and material stack caused by abnormal leakage for the products in-situ. The diagnosis accuracy for the case studies explored here using BPNN is greater than 95%. Results from the experiments show that the proposed approach can accurately recognize the machine failures and quality defects during the FFF process, thus effectively assuring the product quality.

16.
Mol Pharmacol ; 94(4): 1164-1173, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30108138

RESUMO

Coumarin osthole is a dominant bioactive ingredient of the natural Cnidium monnieri plant commonly used for traditional Chinese herbal medicines for therapies and treatments including antipruritus and antidermatitis. However, the molecular mechanism underlying the action of osthole remains unclear. In this study, we report that osthole exerts an antipruritic effect through selective inhibition of Ca2+-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) cation channels that are primarily expressed in the keratinocytes of the skin. Coumarin osthole was identified as an inhibitor of TRPV3 channels transiently expressed in HEK293 cells in a calcium fluorescent assay. Inhibition of the TRPV3 current by osthole and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV3-expressing HEK293 cells and mouse primary cultured keratinocytes. Behavioral evaluation demonstrated that inhibition of TRPV3 by osthole or silencing by knockout of the TRPV3 gene significantly reduced the scratching induced by either acetone-ether-water or histamine in localized rostral neck skin in mice. Taken together, our findings provide a molecular basis for use of natural coumarin osthole from the C. monnieri plant in antipruritic or skin care therapy, thus establishing a significant role of the TRPV3 channel in chronic itch signaling or acute histamine-dependent itch sensation.


Assuntos
Antipruriginosos/farmacologia , Cumarínicos/farmacologia , Prurido/tratamento farmacológico , Pele/efeitos dos fármacos , Pele/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Linhagem Celular , Células HEK293 , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prurido/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Acta Pharmacol Sin ; 39(3): 331-335, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29094727

RESUMO

Itching is an intricate, common symptom of dermatologic and systemic diseases, and both TRPV3 and TRPA1 channels have been suggested to function as downstream effector targets. But the relative contributions of TRPV3 and TRPA1 to itch sensation in vivo remain unclear. To dissect the role of TRPA1 or TRPV3 in the cutaneous sensation of itching, we took the advantage of a natural compound carvacrol from oregano, and examined its effect on the induction of scratching behavior in mice. We showed that the intradermal injection of carvacrol (0.01%, 0.1% and 1%, 50 µL) induced scratching in a concentration-dependent manner. But in TRPV3-knockout mice, the scratching induced by carvacrol (1%, 50 µL) was markedly decreased by approximately 64% (from 275 scratching bouts down to 90) within 60 min. Further analysis revealed that TRPV3-knockout caused a reduction of scratching bouts for approximately 40% in the first 20 min (the initial phase), whereas the scratching bouts were reduced by approximately 90% in the last 40 min (the sustained phase). These results were in consistence with those in our whole-cell recordings in HEK-293T cells expressing either TRPA1 or TRPV3: carvacrol exhibited similar potencies in activating either TRPA1 or TRPV3, but carvacrol-activated TRPA1 current showed a rapid desensitization, which was reduced by approximately 90% within 5 min before a complete washout, whereas carvacrol-induced TRPV3 current showed a slow desensitization that caused less than 30% of current reduction in 10 min and left a significant residual TRPV3 current after washout. Our results demonstrate that carvacrol from plant oregano is a skin sensitizer or allergen; TRPV3 is involved in the initial phase and the sustained phase of pruritus, whereas TRPA1 likely contributes to the initial phase.


Assuntos
Monoterpenos/farmacologia , Prurido/induzido quimicamente , Prurido/fisiopatologia , Canal de Cátion TRPA1/fisiologia , Canais de Cátion TRPV/fisiologia , Animais , Células Cultivadas , Cimenos , Relação Dose-Resposta a Droga , Humanos , Injeções Intradérmicas , Masculino , Camundongos , Camundongos Knockout , Monoterpenos/administração & dosagem , Canais de Cátion TRPV/genética
18.
Learn Mem ; 24(11): 602-606, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29038222

RESUMO

The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA circuit in IA memory consolidation is unclear. This study investigated the effect of post-training reversible disconnection of the VH-BLA circuit in IA memory consolidation. Male Wistar rats with implanted guide cannulae were trained with a one-trial IA task, then received immediate intracerebral injections of muscimol or saline, and were tested 24 h later. Muscimol injection into the bilateral BLA, or the unilateral VH and contralateral BLA, but not the unilateral VH and ipsilateral BLA, significantly decreased the retention latencies (versus saline treatment). The results suggest that the VH-BLA circuit could be an important circuit to modulate consolidation of IA memory in rats.


Assuntos
Aprendizagem da Esquiva/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Hipocampo/fisiologia , Consolidação da Memória/fisiologia , Análise de Variância , Animais , Atropina/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Relação Dose-Resposta a Droga , Agonistas de Receptores de GABA-A/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Consolidação da Memória/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Muscimol/farmacologia , Ratos , Ratos Wistar
19.
Zhonghua Nan Ke Xue ; 24(7): 618-621, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30173445

RESUMO

OBJECTIVE: To investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV). METHODS: This study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA. RESULTS: Compared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (ï¼»255.18 ± 69.97ï¼½ vs ï¼»141.78 ± 59.82ï¼½ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (ï¼»255.18 ± 69.97ï¼½ vs ï¼»412.44 ± 259.42ï¼½ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = -0.224, P < 0.01). CONCLUSIONS: The level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.


Assuntos
Inibinas/sangue , Varicocele/sangue , Adolescente , Anticorpos/sangue , Biomarcadores/sangue , Criança , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Espermatozoides/imunologia , Testosterona/sangue
20.
Tumour Biol ; 37(11): 14553-14563, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27631965

RESUMO

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.


Assuntos
Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , RNA Longo não Codificante/genética
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