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1.
Epilepsia Open ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898786

RESUMEN

OBJECTIVE: To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). METHODS: We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long-term outcomes after surgical or nonsurgical (anti-seizure medications, ASMs) treatment. RESULTS: A total of 70 patients (49 surgical, 21 non-surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0-4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow-up (median 14.1 years), the rates of seizure-freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure-freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. SIGNIFICANCE: In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. PLAIN LANGUAGE SUMMARY: We aim to summarize clinical characteristics and compare the long-term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

2.
Sci Total Environ ; 946: 174073, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38909802

RESUMEN

Superhydrophobic porous organic polymers are potential sorbents for volatile organic compounds (VOCs) pollution control by suppressing the competition of water molecules on their surfaces. However, the synthesis of superhydrophobic reagents usually requires large amounts of organic solvents and a long reaction time (≥ 24 h). Herein, a green mechanochemical method was developed to synthesize a superhydrophobic polymer (MSHMP-1) with the advantages of using a small amount of organic solvents (5 mL/g) and a short reaction time (2 h). Meanwhile, MSHMP-1 with a water contact angle (WCA) of 162° exhibited a dramatically rich pore structure as revealed by its specific surface area (SSA) of 1780 m2/g. The decrease in the adsorption of benzene on MSHMP-1 due to the competition of water molecules, even at relative humidity of 90 %, was nonsignificant (<10 %), indicating the great application potential of MSHMP-1 in hydrophobic adsorption. Moreover, the adsorption capacity of MSHMP-1 was maintained after at least five adsorption-desorption cycles. Therefore, MSHMP-1 can be a remarkable adsorbent for the removal of hazardous VOCs, especially at high humidity levels.

3.
Int J Biol Macromol ; 244: 125207, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37276904

RESUMEN

In order to further improve the economic benefits of the coffee industry chain, we carried out the following systematic research on processing by-products. In this research, the obtained coffee cherry peel polysaccharide (CCP) which was removed from the coffee cherry peel by hot acid method had a galacturonic acid content of 20.50 % and a molecular weight of 3.05 kg/mol. According to the results of monosaccharide analysis, Fourier transform infrared spectroscopy, molecular weight distribution, and thermal analysis, CCP was a typical high methoxy polysaccharide. In vitro antioxidant results showed that CCP had better antioxidant capacity than commercial citrus polysaccharide (APC). When it came to emulsification performance, the water-oil bonding ability and disturbance resistance to the fluid of CCP were also significantly higher than that of APC. Specially, we found that 0.50 % (wt%) CCP could form a solid-liquid gel with very high plasticity at low oil phase fraction. In conclusion, the coffee cherry peel could be used as a natural source of a novel emulsifier, providing a promising alternative for polysaccharide in the food industry.


Asunto(s)
Antioxidantes , Café , Antioxidantes/farmacología , Antioxidantes/química , Café/química , Polisacáridos/química , Espectroscopía Infrarroja por Transformada de Fourier , Monosacáridos
4.
Environ Geochem Health ; 45(8): 6231-6243, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37280504

RESUMEN

The stabilization of heavy metals in soil has been increasingly applied in China in recent years due to its quick effect and low cost. In this study, loess and chicken manure compost (a commercial organic fertilizer) were used to stabilize Cd in slightly polluted fluvo-aquic soil from the North China Plain, and the driving factors for stabilization were investigated through ridge regression. The additives significantly reduced the total concentration of Cd in soil through dilution. The addition of loess and compost increased carbonates and organic matter in soil, respectively. This caused exchangeable Cd to be transformed to fractions bound to carbonates or organic matter, thereby decreasing the concentration of Cd in the roots and leaves of Chinese chive. The decreasing exchangeable Cd in soil was the direct cause of decreased uptake of Cd by plants, and the increasing fractions bound to carbonates or organic matter were indirect influencing factors. However, adding loess decreased soil fertility and retarded plant growth. The addition of compost compensated for these defects. This study suggests that the combined addition of loess and chicken manure compost was able to effectively reduce the total concentration and phytoavailability of Cd in soil and guarantee crop yield and quality.


Asunto(s)
Cadmio , Cebollino , Compostaje , Contaminantes del Suelo , Animales , Cadmio/química , Pollos , Cebollino/química , Estiércol , Suelo , Contaminantes del Suelo/análisis
5.
Environ Sci Pollut Res Int ; 30(29): 74372-74385, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37208508

RESUMEN

In this study, the spatiotemporal distribution of microplastic deposition was investigated through ordinary Kriging interpolation, and the potential sources of microplastic deposition were identified by using Hybrid Single-Particle Lagrangian Integrated Trajectory model. The results showed that the total deposition flux of microplastics ranged from 79.5 to 810.0 p/(m2·d). The shapes of microplastics could be divided into 4 shapes: fiber, fragment, film, and pellet. Seven polymer types of microplastics were identified, including polyamide (PA), polyethylene (PE), polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polypropylene (PP), polystyrene (PS), and polyvinyl chloride (PVC). Most microplastics were tiny and small sizes (≤ 500 µm) and colorless. Through model analysis and survey, microplastic deposition came from the study region, and the potential sources might be plastic products and wastes. The seasons with the highest and lowest total deposition flux were summer (535.5 p/(m2·d)) and winter (197.5 p/(m2·d)), respectively. The months of the highest and lowest total deposition flux were June 2021 (681.4 p/(m2·d)) and January 2022 (112.2 p/(m2·d)), respectively. Most fibers (PET, PA, PP) and fragments (PP) were distributed in populous areas such as commercial centers and residential areas. Abundant fragments (PET, PS, PE) and films (PE, PVC) were distributed around salvage stations. Almost all of the pellets (PE, PMMA) were found in the factory. Our results suggested that the temporal distribution of microplastic deposition was influenced by precipitation and mean temperature of air, and the spatial distribution of microplastic deposition was influenced by sources and population density.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Plásticos , Polimetil Metacrilato , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Polipropilenos , Poliestirenos , Polietileno/análisis , Nylons , China , Tereftalatos Polietilenos
6.
Epilepsia Open ; 8(3): 898-911, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37144544

RESUMEN

OBJECTIVE: Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new and rare histopathological entity of cortical developmental malformations. The clinical characteristics of MOGHE remain challenging. METHODS: Children with histologically confirmed MOGHE were retrospectively studied. The clinical findings, electroclinical and imaging features, and postoperative outcomes were analyzed, and previously published studies were reviewed up to June 2022. RESULTS: Thirty-seven children were included in our cohort. Clinical characteristics included early onset in infancy (94.6% before 3 years), multiple seizure types, and moderate or severe delay. Epileptic spasm is the most common seizure type and initial manifestation. The lesions were mainly multilobar (59.5% multiple lobes and 8.1% hemispheres), and predominance in the frontal lobe was observed. The interictal EEG pattern was circumscribed or widespread. The prominent MRI characteristics were cortical thickening, cortical/subcortical hyperintense T2/FLAIR signal, and blurring at the GM and WM transition. Among the 21 children followed up for more than 1 year after surgery, 76.2% were seizure-free. Preoperative interictal circumscribed discharges and larger resections were significantly associated with a good postoperative outcome. The clinical features of 113 patients in the reviewed studies were similar to those we reported, but the lesions were mainly unilobar (73.5%) and Engel I was achieved in only 54.2% after surgery. SIGNIFICANCE: Distinct clinical characteristics in MOGHE, especially age at onset, epileptic spasm, and age-related MRI characteristics, can help in early diagnosis. Preoperative interictal discharge and surgical strategy may be predictors of postoperative outcomes.


Asunto(s)
Epilepsia , Espasmos Infantiles , Humanos , Niño , Estudios Retrospectivos , Hiperplasia/cirugía , Electroencefalografía , Epilepsia/cirugía , Resultado del Tratamiento , Espasmo
7.
Sci Rep ; 12(1): 20737, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36456645

RESUMEN

Lung Squamous Cell Carcinoma (LUSC) is an aggressive malignancy with limited therapeutic options. The response to immune therapy is a determining factor for the prognosis of LUSC patients. This study aimed to develop a reliable immune-related prognostic signature in LUSC. We extracted gene expression and clinical data of LUSC from The Cancer Genome Atlas (TCGA). A total of 502 patients enrolled and were divided into respond and non-responder groups by the TIDE algorithm. The CIBERSORT algorithm and the LM22 gene signature were used to analyze the distribution of immune cells in LUSC. Efficacy and response strength of immunotherapy are calculated by the tumor mutation burden (TMB) and ESTIMATE Score. Differentially expressed genes (DEGs) between the two groups were analyzed. The differential expression genes related to overall survival were pointed as hub DEGs, and a prognostic signature was constructed with lasso regression analysis. LUSC patients were divided into responder and non-responder groups based on the response to immunotherapy. The distribution of immune cells was significantly different between the two groups. Forty-four DGEs were considered as overall survival-related genes. A prognostic signature was constructed, consisting of 11 hub-DGEs, including MMP20, C18orf26, CASP14, FAM71E2, OPN4, CGB5, DIRC1, C9orf11, SPATA8, C9orf144B, and ZCCHC5. The signature can accurately distinguish LUSC patients into high and low-risk groups. Moreover, the high-risk group had a shorter survival time than the low-risk group. The area under the ROC curve was 0.67. The multivariate Cox regression showed that the risk score calculated by the constructed signature was an independent prognostic predictor for LUSC patients. In short, we established a novel immune-related prognostic signature in LUCS, which has significant sensitivity and accuracy in predicting the prognosis of patients. Our research can guide the evaluation of the prognosis of LUSC patients in clinical, and the discovered immune-related genes can provide a theoretical basis for the discovery of new therapeutic targets.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Pronóstico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Pulmón
8.
Cell Rep ; 41(1): 111444, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36198265

RESUMEN

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival of social animals. Gastrin-releasing peptide (GRP) and its receptor (GRPR) in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates contagious itch behavior in mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual itch information, independently of melanopsin, from the retina to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR neurons relay itch information to the paraventricular nucleus of the thalamus (PVT). Surprisingly, neither the visual cortex nor superior colliculus is involved in contagious itch. In vivo calcium imaging and extracellular recordings reveal contagious itch-specific neural dynamics of GRPR neurons. Thus, we propose that the retina-ipRGC-SCN-PVT pathway constitutes a previously unknown visual pathway that probably evolved for motion vision that encodes salient environmental cues and enables animals to imitate behaviors of conspecifics as an anticipatory mechanism to cope with adverse conditions.


Asunto(s)
Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Vías Visuales , Animales , Calcio/metabolismo , Péptido Liberador de Gastrina/metabolismo , Ratones , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Prurito/metabolismo , Retina/metabolismo , Células Ganglionares de la Retina/metabolismo , Núcleo Supraquiasmático/metabolismo , Vías Visuales/metabolismo
9.
Comput Struct Biotechnol J ; 20: 5001-5013, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36187916

RESUMEN

Background: There are currently no treatments targeting the immune microenvironment (TME) as an extension of immunotherapy. Our research aims to provide guidance for the development of immune-related mRNA vaccines and the identification of immune subtypes for vaccine treatment in lung adenocarcinoma (LUAD). Methods: HTRNA-Seq and single cell RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus (GEO, GSE87340, GSE140343, GSE148071) databases. Immune checkpoints (ICP) were used as criteria to differentiate immune subtypes and immune resistance score (IRS) system is constructed by ssGSEA to judge the immune microenvironment status of patients. Results: Two overexpressed tumor-specific antigens, including ZC3H12D and TXNDC5, were found to be associated with both disease-free survival (DFS) and overall survival (OS). In addition, the expression of two genes correlated with antigen-presenting cell (APC) infiltration and tumor purity. Subsequently, the immune subtype of the patient was defined by constructing an IRS scoring system. The lower the IRS, the stronger the immune response in the TME. This result was verified in external datasets and at the single-cell level. Conclusions: ZC3H12D and TXNDC5 are potential tumor-specific antigens for developing mRNA vaccines in LUAD. Importantly, patients with low IRS are more suitable for the use of immunotherapy and vaccines. Our research enhances understanding of TME features and guides more effective immunotherapy strategies.

10.
Cancer Cell Int ; 22(1): 59, 2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35115004

RESUMEN

BACKGROUND: The prevalence of lung adenocarcinoma (LUAD) has increased, thus novel biomarkers for its early diagnosis is becoming more important than ever. tRNA-derived small RNA (tsRNA) is a new class of non-coding RNA which has important regulatory roles in cancer biology. This study was designed to identify novel predictive and prognostic tsRNA biomarkers. METHODS: tsRNAs were identified and performed differential expression analysis from 10 plasma samples (6 LUAD and 4 normal, SRP266333) and 96 tissue samples (48 LUAD and 48 normal, SRP133217). Then a tsRNA-mRNA regulatory network was constructed to find hub tsRNAs. Functional enrichment analysis was performed to infer the potential pathways associated with tsRNAs. Afterwards, a Support Vector Machine (SVM) algorithm was used to explore the potential biomarkers for diagnosing LUAD. Lastly, the function of tRF-21-RK9P4P9L0 was explored in A549 and H1299 cell lines. RESULTS: A significant difference of read distribution was observed between normal people and LUAD patients whether in plasma or tissue. A tsRNA-mRNA regulatory network consisting of 155 DEtsRNAs (differential expression tsRNAs) and 406 DEmRNAs (differential expression mRNAs) was established. Three tsRNAs (tRF-16-L85J3KE, tRF-21-RK9P4P9L0 and tRF-16-PSQP4PE) were identified as hub genes with degree > 100. We found Co-DEmRNAs (intersection of DEtsRNAs target mRNAs and differentially expressed mRNAs in LUAD) were engaged in a number of cancer pathways. The AUC of the three hub tsRNAs' expression for diagnosing LUAD reached 0.92. Furthermore, the qPCR validation of the three hub tsRNAs in 37 paired normal and LUAD tissues was consistent with the RNA-Seq results. In addition, tRF-21-RK9P4P9L0 was negatively associated with LUAD prognosis. Inhibition of tRF-21-RK9P4P9L0 expression reduced the proliferation, migration and invasion ability of A549 and H1299 cell lines. CONCLUSION: These findings will help us further understand the molecular mechanisms of LUAD and contribute to novel diagnostic biomarkers and therapeutic target discovery.

11.
Cell Death Discov ; 7(1): 249, 2021 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-34537813

RESUMEN

tRNAs are a group of conventional noncoding RNAs (ncRNAs) with critical roles in the biological synthesis of proteins. Recently, tRNA-derived small RNAs (tsRNAs) were found to have important biological functions in the development of human diseases including carcinomas, rather than just being considered pure degradation material. tsRNAs not only are abnormally expressed in the cancer tissues and serum of cancer patients, but also have been suggested to regulate various vital cancer hallmarks. On the other hand, the application of tsRNAs as biomarkers and therapeutic targets is promising. In this review, we focused on the basic characteristics of tsRNAs, and their biological functions known thus far, and explored the regulatory roles of tsRNAs in cancer hallmarks including proliferation, apoptosis, metastasis, tumor microenvironment, drug resistance, cancer stem cell phenotype, and cancer cell metabolism. In addition, we also discussed the research progress on the application of tsRNAs as tumor biomarkers and therapeutic targets.

12.
Front Oncol ; 11: 654995, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34094948

RESUMEN

Lung cancer is the most frequently diagnosed cancer and the main cause of cancer death in the world. X-box binding protein 1 (XBP1), which is an important transcription factor involved in regulating the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, might act as a potent oncogenic protein in the processes of tumorigenesis, tumor proliferation and metastasis in various cancers. However, the clinical significance and pathological role of XBP1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the expression of XBP1s protein in the 104 NSCLC tumor tissues and matched adjacent normal lung tissues (ANLT) by Immunohistochemical (IHC), and we found overexpressed XBP1s protein was associated with NSCLC TNM stages, lymph node metastasis and poor prognosis. The further gain-and loss-of-function experiments indicated overexpression of XBP1s protein promoted cell invasion, migration and metastasis both in vitro and in vivo. Further study showed XBP1s protein could upregulate insulin-like growth factor binding protein-3 (IGFBP3) expression, and regulated NSCLC cells invasion and metastasis by regulating IGFBP3. Taken together, XBP1s protein is markedly overexpressed in NSCLC and serves as an oncogene that play a critical role in NSCLC tumorigenesis and development. Importantly, XBP1s protein might not only be a potential biomarker for metastasis and prognosis but also a potential therapeutic target in NSCLC.

13.
RSC Adv ; 11(46): 28632-28642, 2021 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-35478593

RESUMEN

In this work, a polypyrrole (PPy)/TiO2 nanocomposite coating was fabricated by the direct electropolymerization of pyrrole on annealed TiO2 nanoparticles and evaluated as a novel direct immersion solid phase microextraction (DI-SPME) fiber coating for extraction of trace amounts of pollutants in environmental water samples. The functionalized fiber is mechanically and chemically stable, and can be easily prepared in a highly reproducible manner. The effects of the pyrrole monomer concentration, polymerization voltage and polymerization time on the fiber were discussed. Surface morphological and compositional analyses revealed that the composite coating of nano polypyrrole and titanium dioxide nanoparticles (TiO2NPs) uniformly doped the Ti substrate. The as-fabricated fiber exhibited good extraction capability for phenolic compounds in combination with high performance liquid chromatography-UV detection (HPLC-UV). At the optimum SPME conditions, the calibration curves were linear (R 2 ≥ 0.9965). LODs and LOQs of less than 0.026 µg L-1 and 0.09 µg L-1 , respectively, were achieved, and RSDs were in the range 3.5-7.2%. The results obtained in this work suggest that PPy/TiO2 is a promising coating material for future applications of SPME and related sample preparation techniques.

14.
Nat Commun ; 11(1): 5074, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33033265

RESUMEN

Touch and itch sensations are crucial for evoking defensive and emotional responses, and light tactile touch may induce unpleasant itch sensations (mechanical itch or alloknesis). The neural substrate for touch-to-itch conversion in the spinal cord remains elusive. We report that spinal interneurons expressing Tachykinin 2-Cre (Tac2Cre) receive direct Aß low threshold mechanoreceptor (LTMR) input and form monosynaptic connections with GRPR neurons. Ablation or inhibition markedly reduces mechanical but not acute chemical itch nor noxious touch information. Chemogenetic inhibition of Tac2Cre neurons also displays pronounced deficit in chronic dry skin itch, a type of chemical itch in mice. Consistently, ablation of gastrin-releasing peptide receptor (GRPR) neurons, which are essential for transmitting chemical itch, also abolishes mechanical itch. Together, these results suggest that innocuous touch and chemical itch information converge on GRPR neurons and thus map an exquisite spinal circuitry hard-wired for converting innocuous touch to irritating itch.


Asunto(s)
Red Nerviosa/fisiopatología , Prurito/fisiopatología , Tacto/fisiología , Animales , Conducta Animal , Inyecciones Espinales , Luz , Potenciales de la Membrana , Ratones Endogámicos C57BL , Neuronas/metabolismo , Precursores de Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Receptores de Bombesina/metabolismo , Piel/patología , Médula Espinal/fisiopatología , Sinapsis/metabolismo , Taquicininas/metabolismo
15.
J Hematol Oncol ; 13(1): 19, 2020 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-32169087

RESUMEN

Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.


Asunto(s)
Carcinogénesis/patología , Neoplasias/irrigación sanguínea , Neovascularización Patológica/patología , Animales , Carcinogénesis/genética , Carcinogénesis/metabolismo , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal
16.
J Invest Dermatol ; 140(8): 1524-1532, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32004565

RESUMEN

Animal studies have suggested that transient receptor potential ion channels and G-protein coupled receptors play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome, which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease-activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists. Moreover, we show that TRPV3 and PAR2 were upregulated in skin biopsies from patients and mice with atopic dermatitis, whereas their inhibition attenuated scratching and inflammatory responses in mouse atopic dermatitis models. These results reveal a previously unrecognized link between TRPV3 and PAR2 in keratinocytes to convey itch information and suggest that a blockade of PAR2 or TRPV3 individually or both may serve as a potential approach for antipruritic therapy in atopic dermatitis.


Asunto(s)
Dermatitis Atópica/complicaciones , Prurito/inmunología , Receptor PAR-2/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Antipruriginosos/farmacología , Antipruriginosos/uso terapéutico , Biopsia , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Modelos Animales de Enfermedad , Mutación con Ganancia de Función , Humanos , Queratinocitos/inmunología , Queratinocitos/patología , Masculino , Ratones , Ratones Noqueados , Prurito/tratamiento farmacológico , Prurito/genética , Prurito/patología , Receptor PAR-2/agonistas , Receptor PAR-2/antagonistas & inhibidores , Receptor PAR-2/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Piel/citología , Piel/inmunología , Piel/patología , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/genética , Regulación hacia Arriba
17.
J Clin Invest ; 123(11): 4769-80, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24216512

RESUMEN

Chronic itch, or pruritus, is associated with a wide range of skin abnormalities. The mechanisms responsible for chronic itch induction and persistence remain unclear. We developed a mouse model in which a constitutively active form of the serine/threonine kinase BRAF was expressed in neurons gated by the sodium channel Nav1.8 (BRAF(Nav1.8) mice). We found that constitutive BRAF pathway activation in BRAF(Nav1.8) mice results in ectopic and enhanced expression of a cohort of itch-sensing genes, including gastrin-releasing peptide (GRP) and MAS-related GPCR member A3 (MRGPRA3), in nociceptors expressing transient receptor potential vanilloid 1 (TRPV1). BRAF(Nav1.8) mice showed de novo neuronal responsiveness to pruritogens, enhanced pruriceptor excitability, and heightened evoked and spontaneous scratching behavior. GRP receptor expression was increased in the spinal cord, indicating augmented coding capacity for itch subsequent to amplified pruriceptive inputs. Enhanced GRP expression and sustained ERK phosphorylation were observed in sensory neurons of mice with allergic contact dermatitis­ or dry skin­elicited itch; however, spinal ERK activation was not required for maintaining central sensitization of itch. Inhibition of either BRAF or GRP signaling attenuated itch sensation in chronic itch mouse models. These data uncover RAF/MEK/ERK signaling as a key regulator that confers a subset of nociceptors with pruriceptive properties to initiate and maintain long-lasting itch sensation.


Asunto(s)
Proteínas Proto-Oncogénicas B-raf/fisiología , Prurito/etiología , Prurito/fisiopatología , Células Receptoras Sensoriales/fisiología , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Péptido Liberador de Gastrina/genética , Péptido Liberador de Gastrina/fisiología , Expresión Génica , Humanos , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Noqueados , Ratones Transgénicos , Canal de Sodio Activado por Voltaje NAV1.8/genética , Canal de Sodio Activado por Voltaje NAV1.8/fisiología , Nociceptores/fisiología , Proteínas Proto-Oncogénicas B-raf/genética , Prurito/genética , Receptores de Bombesina/genética , Receptores de Bombesina/fisiología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/fisiología , Médula Espinal/fisiopatología , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/fisiología
18.
Neurosci Bull ; 26(2): 163-7, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20332822

RESUMEN

Galphai/o protein-coupled dopamine D3 receptors (D3Rs) are preferentially expressed in the limbic system, including the nucleus accumbens. This situates the receptor well in the regulation of limbic function and in the pathogenesis of various neuropsychiatric and neurodegenerative disorders. The intracellular domains of the receptor, mainly the large third intracellular loop and the intracellular C-terminal tail, interact with multiple submembranous proteins. These interactions are critical for the control of surface expression of the receptor and the efficacy of receptor signaling. Recently, a synapse-enriched protein kinase, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), has been found to interact with D3R in the above mentioned interaction model. CaMKII directly binds to the N-terminal of the third loop of D3R. This binding is Ca(2+)-dependent and is sustained by the autophosphorylation of the kinase. In rat accumbal neurons, the increase in Ca(2+) level induces the recruitment of CaMKII to D3R, and CaMKII phosphorylates the receptor at a specific serine site. The CaMKII-induced phosphorylation could inhibit the receptor function and further regulate the behavioral response to the psychostimulant cocaine. These findings reveal a prototypic protein association model between a G protein-coupled receptor and CaMKII. Through the dynamic protein-protein interactions, the abundance, turnover cycle, and function of D3R can be regulated by multiple signals and enzymatic proteins.


Asunto(s)
Sistema Límbico/metabolismo , Receptores de Dopamina D3/metabolismo , Transducción de Señal/fisiología , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , AMP Cíclico/metabolismo , Humanos , Modelos Biológicos , Fosforilación , Unión Proteica , Dominios y Motivos de Interacción de Proteínas/fisiología
19.
Neurochem Res ; 33(10): 1956-63, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18404373

RESUMEN

In China, it has been estimated that there are more than 2.0 million people suffering from Parkinson's disease, which is currently becoming one of the most common chronic neurodegenerative disorders during recent years. For many years, scientists have struggled to find new therapeutic approaches for this disease. Since 1994, our research group led by Drs. Ji-Sheng Han and Xiao-Min Wang of Neuroscience Research Institute, Peking University has developed several prospective treatment strategies for the disease. These studies cover the traditional Chinese medicine-herbal formula or acupuncture, and modern technologies such as gene therapy or stem cell replacement therapy, and have achieved some original results. It hopes that these data may be beneficial for the research development and for the future clinical utility for treatment of Parkinson's disease.


Asunto(s)
Electroacupuntura , Terapia Genética , Medicina Tradicional China , Enfermedad de Parkinson/terapia , Trasplante de Células Madre , Animales , Diterpenos/uso terapéutico , Compuestos Epoxi/uso terapéutico , Glutamato Descarboxilasa/genética , Humanos , Fenantrenos/uso terapéutico
20.
Ai Zheng ; 26(12): 1357-9, 2007 Dec.
Artículo en Chino | MEDLINE | ID: mdl-18076801

RESUMEN

BACKGROUND & OBJECTIVE: Morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet are preferred medicines for treating moderate-severe cancer pain. There are some differences between the two medicines in their efficacy, metabolism and adverse events. This study was to compare the efficacy and toxicities between morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet in treating moderate-severe cancer pain. METHODS: A total of 121 patients with moderate-severe cancer pain were randomized into two groups: 61 were treated with morphine sulfate controlled-released tablet and 60 were treated with morphine hydrochloride sustained-released tablet. Analgesic efficacy and toxicities of the two medicines were observed. RESULTS: Of the 61 patients treated with morphine sulfate controlled-released tablet, 12 had moderate pain, 49 had severe pain; the total response rate was 91.80%. Of the 60 patients treated with morphine hydrochloride sustained-released tablet, 13 had moderate pain, 47 had severe pain; the total response rate was 91.67%. There was no significant difference in the efficacy between the two medicines. Digestive system adverse events, including nausea, vomiting and constipation, were more common in morphine hydrochloride sustained-released tablet group than in morphine sulfate controlled-released tablet group (66.66% vs. 34.43%, P<0.05). CONCLUSIONS: Both morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet are safety in treating moderate-severe cancer pain and the toxicities are tolerable. We recommend to take morphine sulfate controlled-released tablet for older patients and the patients with digestive disorders.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Morfina/uso terapéutico , Neoplasias/complicaciones , Dolor/tratamiento farmacológico , Adolescente , Adulto , Anciano , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/clasificación , Estreñimiento/inducido químicamente , Preparaciones de Acción Retardada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Morfina/efectos adversos , Morfina/clasificación , Náusea/inducido químicamente , Dolor/etiología , Dimensión del Dolor , Resultado del Tratamiento , Vómitos/inducido químicamente , Adulto Joven
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