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1.
J Immunol ; 212(3): 410-420, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088802

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a persistent and irreversible side effect of antineoplastic agents. Patients with CIPN usually show chronic pain and sensory deficits with glove-and-stocking distribution. However, whether spinal neuronal microRNA (miR)-124 is involved in cisplatin-induced peripheral neuropathy remains to be studied. In this study, miR-124 was significantly reduced in the spinal dorsal horn in CIPN mice. Overexpression of neuronal miR-124 induced by injecting adeno-associated virus with neuron-specific promoter into the spinal cord of mice prevented the development of mechanical allodynia, sensory deficits, and the loss of intraepidermal nerve fibers induced by cisplatin. Meanwhile, cisplatin-induced M1 microglia activation and the release of proinflammatory cytokines were significantly inhibited by overexpression of neuronal miR-124. Furthermore, electroacupuncture (EA) treatment upregulated miR-124 expression in the spinal dorsal horn of CIPN mice. Interestingly, downregulation of spinal neuronal miR-124 significantly inhibited the regulatory effect of EA on CIPN and microglia activity as well as spinal neuroinflammation induced by cisplatin. These results demonstrate that spinal neuronal miR-124 is involved in the prevention and treatment of EA on cisplatin-induced peripheral neuropathy in mice. Our findings suggest that spinal neuronal miR-124 might be a potential target for EA effect, and we provide, to our knowledge, a new experimental basis for EA prevention of CIPN.


Assuntos
Antineoplásicos , Eletroacupuntura , MicroRNAs , Doenças do Sistema Nervoso Periférico , Humanos , Camundongos , Animais , Cisplatino/toxicidade , Microglia , Paclitaxel/efeitos adversos , Antineoplásicos/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/prevenção & controle , Neurônios/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
2.
Scand J Gastroenterol ; 59(5): 524-532, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38294208

RESUMO

BACKGROUND: Oxyntic gland neoplasm (OGN) is a rare subtype of gastric cancer. The aim of this study is to evaluate the prevalence, clinicopathological features, effectiveness and safety of endoscopic treatment, as well as the prognosis of OGN. METHODS: We retrospectively analyzed the data of patients pathologically diagnosed with OGN at our hospital from November 1, 2019 to May 1, 2023. RESULTS: A total of 36 patients with 45 lesions were identified, resulting in a disease frequency of 0.047% (36/76,832). The mean age was 55.0 ± 7.5 years, with a male-to-female ratio of about 1:1.12. Most lesions were ≤10 mm in size (84.4%), located in the upper third of the stomach (73.3%), exhibited slight elevation (75.5%), appeared whitish (55%), had dilated blood vessels on the surface (75.5%). 16 and 21 lesions were treated by precutting endoscopic mucosal resection (EMR-P) and endoscopic submucosal dissection (ESD), respectively. No significant differences were found between EMR-P and ESD in terms of en bloc resection rate (100% vs 100%, p = 1.000), complete resection rate (100% vs 90.5%, p = 0.495), and curative resection rate (93.8% vs 90.5%, p = 1.000). No complications such as bleeding and perforation were observed. No recurrence or metastasis was observed during the follow-up period. CONCLUSIONS: OGN is a rare tumor with unique clinical, endoscopic, and pathological characteristics. EMR-P and ESD are deemed safe and effective for treating OGNs. The relatively faster and easier EMR-P seems at least non-inferior to ESD, especially for removal of smaller OGNs. The overall prognosis is favorable.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/epidemiologia , Prevalência , Idoso , Resultado do Tratamento , Adulto , Prognóstico , Gastroscopia , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , China/epidemiologia
3.
Acta Pharmacol Sin ; 44(4): 766-779, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36229601

RESUMO

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin (CAP), the main component of chili pepper. Despite studies in several neurological diseases, the role of TRPV1 in demyelinating diseases remains unknown. Herein, we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone (CPZ)-induced demyelination mouse model. TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice, whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination. TRPV1 was predominantly expressed in Iba1+ microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions. TRPV1 deficiency decreased microglial recruitment to the corpus callosum, with an associated increase in the accumulation of myelin debris. Conversely, the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance. Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment. In addition, the expression of the scavenger receptor CD36 was increased, and that of the glycolysis regulators Hif1a and Hk2 was decreased. We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Animais , Humanos , Camundongos , Cuprizona , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Bainha de Mielina/metabolismo , Canais de Cátion TRPV , Capsaicina/farmacologia
4.
Anesth Analg ; 134(1): 204-215, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652301

RESUMO

BACKGROUND: The main symptoms of chemotherapy-induced peripheral neuropathy (CIPN) include pain and numbness. Neuronal G protein-coupled receptor kinase 2 (GRK2) plays an important role in various pain models. Cisplatin treatment can induce the activation of proinflammatory microglia in spinal cord. The purpose of this study was to investigate the role of spinal neuronal GRK2 in cisplatin-induced CIPN and in the prevention of CIPN by electroacupuncture (EA). METHODS: The pain and sensory deficit behaviors of mice were examined by von Frey test and adhesive removal test. The expression of neuronal GRK2 in the spinal cord is regulated by intraspinal injection of adeno-associated virus (AAV) containing neuron-specific promoters. The protein levels of GRK2, triggering receptor expressed on myeloid cells 2 (TREM2), and DNAX-activating protein of 12 kDa (DAP12) in spinal dorsal horn were detected by Western blot, the density of intraepidermal nerve fibers (IENFs) was detected by immunofluorescence, and microglia activation were evaluated by real-time polymerase chain reaction (PCR). RESULTS: In this study, cisplatin treatment led to the decrease of GRK2 expression in the dorsal horn of spinal cord. Overexpression of neuronal GRK2 in spinal cord by intraspinal injection of an AAV vector expressing GRK2 with human synapsin (hSyn) promotor significantly inhibited the loss of IENFs and alleviated the mechanical pain and sensory deficits induced by cisplatin. Real-time PCR analysis showed that the overexpression of neuronal GRK2 significantly inhibited the messenger RNA (mRNA) upregulation of proinflammatory cytokine interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), and M1 microglia marker cluster of differentiation (CD)16 induced by cisplatin. Furthermore, the TREM2 and DAP12, which has been demonstrated to play a role in microglia activation and in the development of CIPN, were also downregulated by overexpression of neuronal GRK2 in this study. Interestingly, preventive treatment with EA completely mimics the effect of overexpression of neuronal GRK2 in the spinal cord in this mouse model of cisplatin-induced CIPN. EA increased GRK2 level in spinal dorsal horn after cisplatin treatment. Intraspinal injection of AAV vector specifically downregulated neuronal GRK2, completely reversed the regulatory effect of EA on CIPN and microglia activation. All these indicated that the neuronal GRK2 mediated microglial activation contributed to the process of CIPN. CONCLUSIONS: Neuronal GRK2 in the spinal cord contributed to the preventive effect of EA on CIPN. The neuronal GRK2 may be a potential target for CIPN intervention.


Assuntos
Cisplatino , Eletroacupuntura , Quinase 2 de Receptor Acoplado a Proteína G/genética , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Medula Espinal/patologia , Animais , Comportamento Animal , Dependovirus , Humanos , Hiperalgesia/metabolismo , Inflamação , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fibras Nervosas , Neuralgia/metabolismo , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Dor , Corno Dorsal da Medula Espinal/metabolismo , Fatores de Tempo
5.
Biol Res ; 55(1): 5, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115050

RESUMO

BACKGROUND: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. METHODS: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and downregulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR. RESULTS: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain. CONCLUSION: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.


Assuntos
Eletroacupuntura , Quinase 2 de Receptor Acoplado a Proteína G/fisiologia , Microglia/fisiologia , Manejo da Dor , Animais , Inflamação/induzido quimicamente , Inflamação/terapia , Camundongos , Neurônios , Dor/induzido quimicamente
6.
Neural Plast ; 2022: 4217593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35211169

RESUMO

Chronic pain patients often develop mental disorders, and anxiety disorders are common. We hypothesize that the comorbid anxiety results from an imbalance between the reward and antireward system due to persistent pain, which leads to the dysfunction of the pain and anxiety regulatory system. In this review, we will focus on changes in neuroplasticity, especially in neural circuits, during chronic pain and anxiety as observed in animal studies. Several neural circuits within specific regions of the brain, including the nucleus accumbens, lateral habenular, parabrachial nucleus, medial septum, anterior cingulate cortex, amygdala, hippocampus, medial prefrontal cortex, and bed nucleus of the stria terminalis, will be discussed based on novel findings after chemogenetic or optogenetic manipulation. We believe that these animal studies provide novel insights into human conditions and can guide clinical practice.


Assuntos
Dor Crônica , Animais , Ansiedade , Transtornos de Ansiedade/epidemiologia , Encéfalo , Dor Crônica/epidemiologia , Comorbidade , Humanos
7.
Lasers Med Sci ; 37(5): 2343-2352, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35404002

RESUMO

Pain is a common symptom of an illness. For decades, pain treatments such as non-steroidal anti-inflammatory drugs, opioids, and surgical nerve blocking have been widely used, but each method has its limitations. Photobiomodulation is a recently developed method for pain management, with light-emitting diodes (LEDs) being a more recent development used in pain management because of their low cost, low side effects, and high safety. Here, we reviewed the phototherapeutic effects of LEDs on different pain conditions. We also discussed possible physicochemical and neurobiological mechanisms underlying LED therapy, especially its effects on inflammatory pain.


Assuntos
Terapia com Luz de Baixa Intensidade , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Dor/radioterapia , Manejo da Dor , Medição da Dor , Fototerapia/métodos
8.
BMC Surg ; 22(1): 417, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36476138

RESUMO

OBJECTIVES: Esophageal cancer is a high-mortality disease. Esophagectomy is the most effective method to treat esophageal cancer, accompanied with a high incidence of post-operation complications. The anastomosis has a close connection to many severe post-operation complications. However, it remains controversial about the choice of intrathoracic anastomosis (IA) or cervical anastomosis (CA). The study was conducted to compare the clinical outcomes between the two approaches. METHODS: We searched databases for both randomized controlled trials (RCTs) and cohort studies comparing post-operation outcomes between IA and CA. Primary outcomes were the incidences of anastomotic leakage and mortality. Secondary outcomes were the incidences of anastomotic stenosis, pneumonia and re-operation. RESULTS: Twenty studies with a total of 7,479 patients (CA group: n = 3,183; IA group: n = 4296) were included. The results indicated that CA group had a higher incidence of anastomotic leakage than IA group (odds ratio [OR] = 2.05, 95% confidence intervals [CI] = 1.61-2.60, I2 = 53.31%, P < 0.01). Subgroup analyses showed that CA group had higher incidences of type I (OR = 2.19, 95%CI = 1.05-4.57, I2 = 0.00%, P = 0.04) and type II (OR = 2.75, 95%CI = 1.95-3.88, I2 = 1.80%, P < 0.01) anastomotic leakage than IA group. No difference was found in type III anastomotic leakage (OR = 1.23, 95%CI = 0.82-1.86, I2 = 20.92%, P = 0.31). The 90-day mortality (OR = 1.66, 95%CI = 1.11-2.47, I2 = 0.0%, P = 0.01) in IA group were lower than that in CA group. No difference was found in in-hospital mortality (OR = 1.31, 95%CI = 0.91-1.88, I2 = 0.00%, P = 0.15) and 30-day mortality (OR = 1.08, 95%CI = 0.69-1.70, I2 = 0.00%, P = 0.74). CONCLUSIONS: IA might be a better anastomotic approach than CA, with a lower incidence of anastomosis leakage and no increase in short-term mortality. Significant heterogeneity and publication bias might limit the reliability of the results. More high-quality studies are needed to verify and update our findings.


Assuntos
Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/cirurgia
9.
J Hum Nutr Diet ; 34(6): 926-934, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33788349

RESUMO

BACKGROUND: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. METHODS: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. RESULTS: The optimal cut-off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32-4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan-Meier curve indicated that patients at high nutritional risk have poorer 365-days [hazard ratio (HR) = 1.76, 95% CI = 1.30-2.37, p < 0.001] and 1000-days (HR = 2.30, 95% CI = 1.87-2.83, p < 0.001) overall survival. CONCLUSIONS: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long-term survival in CSRU patients. More well-designed clinical trials are needed to verify and update our findings.


Assuntos
Desnutrição , Avaliação Nutricional , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Desnutrição/diagnóstico , Estado Nutricional , Prognóstico , Estudos Retrospectivos , Medição de Risco
10.
BMC Med Inform Decis Mak ; 21(1): 121, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832470

RESUMO

BACKGROUND: The motion capture has been used as the usual method for measuring movement parameters of human, and most of the measuring data are obtained by partial manual process based on commercial software. An automatic kinematics data process was developed by programming on MATLAB software in this paper. METHODS: The motion capture measurement of healthy volunteers was carried out and the MATLAB program was used for data process. Firstly, the coordinate data of markers and anatomical points on human lower limb measured by motion capture system were read and repaired through the usual and the patch program. Meantime, the local coordinate systems of human femur and tibia were established with anatomical points. Then flexion/extension, abduction/adduction and internal/external rotation of human knee tibiofemoral joint were obtained by special coordinate transformation program. RESULTS: Using the above methods, motion capture measurements and batch data processing were carried out on squatting and climbing stairs of 29 healthy volunteers. And the motion characteristics (flexion/extension, internal/external rotation and adduction/abduction) of the knee joint were obtained. For example, the maximum internal/external rotation in squatting and climbing stairs were respectively was 30.5 degrees and 14 degrees, etc. Meantime, the results of this paper also were respectively compared with the results processed by other research methods, and the results were basically consistent, thus the reliability of our research method was verified. After calibration processing, the compiled MATLAB program of this paper can directly be used for efficient batch processing and avoiding manual modeling one by one. CONCLUSION: A novel Patch Program of this paper has been developed, which can make reasonable compensation for missing and noise signals to obtain more complete motion data. At the same time, a universal data processing program has also been developed for obtaining the relative movement of various components of the human body, and the program can be modified for detail special analysis. These motion capture technologies can be used to judge whether the human body functions are abnormal, provide a reference for rehabilitation treatment and design of rehabilitation equipment, and evaluate the effectiveness before and after surgery.


Assuntos
Artroplastia do Joelho , Fenômenos Biomecânicos , Humanos , Articulação do Joelho/cirurgia , Amplitude de Movimento Articular , Reprodutibilidade dos Testes , Rotação
11.
Yi Chuan ; 43(10): 988-993, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702711

RESUMO

The Genome Sequence Archive for Human (GSA-Human) is a data repository specialized for human genetic related data derived from biomedical researches, and also supports the data collection and management of National Key Research and Development Projects. GSA-Human has a data security management strategy according to the national regulations of human genetic resources. It provides two different models of data access: Open-access and Controlled-access. Open-access data are universally and freely accessible for global researchers, while Controlled-access ensures that data are accessed only by authorized users with the permission of the Data Access Committee (DAC). Till July 2021, GSA-Human has housed more than 5.27 PB of data from 750 datasets.

12.
Toxicol Appl Pharmacol ; 406: 115137, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682830

RESUMO

Pyrrolizidine alkaloids (PAs) are a group of hepatic toxicant widely present in plants. Cytochrome P450 (CYP) 3A plays a key role in metabolic activation of PAs to generate electrophilic metabolites, which is the main cause of hepatotoxicity. We have previously demonstrated the sex difference in developmental toxicity and hepatotoxicity in fetal rats exposed to monocrotaline (MCT), a representative toxic PA. The aim of this study was to explore the underlying mechanism. 20 mg·kg-1·d-1 MCT was intragastrically given to pregnant Wistar rats from gestation day 9 to 20. CYP3As expression and pregnane X receptor (PXR) activation were specifically enhanced in female fetal liver. After MCT treatment, we also observed a significant increase of CYP3As expression in LO2 cells (high PXR level) or hPXR-transfected HepG2 cells (low PXR level). Employing hPXR and CYP3A4 dual-luciferase reporter gene assay, we confirmed the agonism effect of MCT on PXR-dependent transcriptional activity of CYP3A4. Agonism and antagonism of the androgen receptor (AR) either induced or blocked MCT-induced PXR activation, respectively. This study was the first report identifying that MCT served as PXR agonist to induce CYP3A expression. CYP3A induction may increase self-metabolic activation of MCT and subsequently lead to more severe hepatotoxicity in female fetus. While in male, during the intrauterine period, activated AR by testosterone secretion from developing testes represses MCT-induced PXR activation and CYP3A induction, which may partially protect male fetus from MCT-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Citocromo P-450 CYP3A/genética , Fígado/efeitos dos fármacos , Monocrotalina/toxicidade , Receptor de Pregnano X/metabolismo , Animais , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/embriologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/metabolismo , Masculino , Troca Materno-Fetal , Gravidez , Ratos Wistar , Caracteres Sexuais
13.
BMC Surg ; 20(1): 127, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522182

RESUMO

BACKGROUND: Castleman's disease (CD) is a rare non-clonal lymphadenopathy. Application of video-assisted thoracoscopic surgery (VATs) in intrathoracic unicentric Castleman's disease (UCD) is rarely reported. This study is aimed to clarify the role of VATs for diagnosis and treatment in intrathoracic UCD. METHODS: The authors reviewed and identified patients who had received a histologic diagnosis of CD through VATs at our hospital from January2010 to June 2018. Clinical and radiologic variables, histopathology, type of approach, complications, and long-term effect were analyzed to evaluate the safety and efficacy of VATs. RESULTS: A total of 10 patients were included in this study, with 8 hyaline vascular type and 2 plasma cell type. The mean maximum diameter of the lesions was 4.66 cm. Nine cases underwent complete surgical excision by VATs, and 1 case was converted to thoracotomy. All patients had no postoperative complications. With a median follow-up of 5 years (range: 1-9 years), no tumor recurrence was found in 9 patients receiving complete tumor resection, and 1 patient with incomplete tumor resection remained symptom free without clinical or radiographic progression. CONCLUSIONS: VATs is an alternative, minimally invasive technique for the diagnosis and treatment in patients with intrathoracic UCD.


Assuntos
Hiperplasia do Linfonodo Gigante , Doenças Torácicas , Cirurgia Torácica Vídeoassistida , Adolescente , Adulto , Idoso , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Torácicas/diagnóstico , Doenças Torácicas/diagnóstico por imagem , Doenças Torácicas/cirurgia , Toracotomia , Veia Cava Superior , Adulto Jovem
14.
Yi Chuan ; 42(2): 212-221, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32102777

RESUMO

An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Bases de Dados Genéticas , Disseminação de Informação , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , COVID-19 , China , Coronavirus , Infecções por Coronavirus/virologia , Genômica , Humanos , Pandemias , Proteômica , SARS-CoV-2
15.
Int Immunol ; 30(7): 311-318, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29939266

RESUMO

B-1 cells are innate-like B-cell population and produce natural antibodies that contribute to the first line of host defense. There are two subsets of B-1 cells: B-1a and B-1b. B-1a cells are the main producer of poly-reactive and autoreactive natural IgM antibodies, whereas B-1b cells can respond specifically to T-cell-independent antigens. Despite the functional significance of B-1a and B-1b cells, little information is available about what regulates the development of these two subsets. We found that Kelch-like protein 14 (KLHL14) was expressed at high levels in B cells but only at low levels in a few non-lymphoid tissues. Although mice lacking KLHL14 died right after birth, the heterozygotes developed normally with no gross abnormalities by appearance. B-cell development in the bone marrow and maturation and activation in the spleen were not affected in the heterozygous mice. However, the number of peritoneal B-1a cells was significantly reduced while B-1b cells were increased in Klhl14 heterozygous mice compared with wild-type (WT) mice. Consistently, Rag1-/- mice reconstituted with Klhl14-/- fetal liver cells had a more severe reduction of B-1a and an increase of B-1b cells in the peritoneal cavity. KLHL14 did not affect the turnover or apoptosis of B-1a and B-1b cells in vivo. Moreover, Klhl14-/- fetal liver contained a similar proportion and absolute numbers of the B-1 progenitor cells as did WT fetal liver. These results suggest that KLHL14 promotes B-1a development in mice.


Assuntos
Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Subpopulações de Linfócitos B/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/deficiência
16.
Anesthesiology ; 131(5): 1125-1147, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567367

RESUMO

BACKGROUND: Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization. METHODS: This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell patch-clamp recordings. The primary outcome was the effect of pharmacologic intervention of spinal vascular endothelial growth factor A/vascular endothelial growth factor receptor 2-signaling on bone cancer pain behaviors. RESULTS: The mRNA and protein expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 were upregulated in tumor-bearing rats. Spinal blocking vascular endothelial growth factor A or vascular endothelial growth factor receptor 2 significantly attenuated tumor-induced mechanical allodynia (mean ± SD: vascular endothelial growth factor A, 7.6 ± 2.6 g vs. 5.3 ± 3.3 g; vascular endothelial growth factor receptor 2, 7.8 ± 3.0 g vs. 5.2 ± 3.4 g; n = 6; P < 0.0001) and thermal hyperalgesia (mean ± SD: vascular endothelial growth factor A, 9.0 ± 2.4 s vs. 7.4 ± 2.7 s; vascular endothelial growth factor receptor 2, 9.3 ± 2.5 s vs. 7.5 ± 3.1 s; n = 6; P < 0.0001), as well as spontaneous pain and abnormal gaits. Exogenous vascular endothelial growth factor A enhanced excitatory synaptic transmission in a vascular endothelial growth factor receptor 2-dependent manner, and spinal injection of exogenous vascular endothelial growth factor A was sufficient to cause pain hypersensitivity via vascular endothelial growth factor receptor 2-mediated activation of protein kinase C and Src family kinase in naïve rats. Moreover, spinal blocking vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 pathways suppressed protein kinase C-mediated N-methyl-D-aspartate receptor activation and Src family kinase-mediated proinflammatory cytokine production. CONCLUSIONS: Vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 contributes to central sensitization and bone cancer pain via activation of neuronal protein kinase C and microglial Src family kinase pathways in the spinal cord.


Assuntos
Neoplasias Ósseas/metabolismo , Dor do Câncer/metabolismo , Medição da Dor/métodos , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Neoplasias Ósseas/patologia , Dor do Câncer/patologia , Feminino , Injeções Espinhais , Medição da Dor/efeitos dos fármacos , Quinazolinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese
17.
J Lipid Res ; 59(1): 35-47, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29113994

RESUMO

Conditional knockout mice with targeted disruption of B-cell associated protein (BAP)31 in adult mouse liver were generated and challenged with a high-fat diet (HFD) for 36 or 96 days and markers of obesity, diabetes, and hepatic steatosis were determined. Mutant mice were indistinguishable from WT littermates, but exhibited increased HFD-induced obesity. BAP31-deletion in hepatocytes increased the expression of SREBP1C and the target genes, including acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1, and increased hepatic lipid accumulation and HFD-induced liver steatosis. Immunoprecipitation assay showed that BAP31 interacts with SREBP1C and insulin-induced gene 1 (INSIG1), and BAP31-deletion reduces INSIG1 expression, suggesting that BAP31 may regulate SREBP1C activity by modulating INSIG1 protein levels. Additionally, BAP31-deletion induced glucose and insulin intolerance, decreased Akt and glycogen synthase kinase 3ß phosphorylation, and enhanced hepatic glucose production in mice. Expression of endoplasmic reticulum (ER) stress markers was significantly induced in BAP31-mutant mice. HFD-induced inflammation was aggravated in mutant mice, along with increased c-Jun N-terminal kinase and nuclear factor-κB activation. These findings demonstrate that BAP31-deletion induces SREBP activation and promotes hepatic lipid accumulation, reduces insulin signaling, impairs glucose/insulin tolerance, and increases ER stress and hepatic inflammation, explaining the protective roles of BAP31 in the development of liver steatosis and insulin resistance in HFD-induced obesity in animal models.


Assuntos
Hepatócitos/metabolismo , Resistência à Insulina , Lipídeos/análise , Fígado/metabolismo , Proteínas de Membrana/deficiência , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Células Hep G2 , Hepatócitos/patologia , Humanos , Lipídeos/genética , Fígado/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/induzido quimicamente , Obesidade/metabolismo , Células Tumorais Cultivadas
18.
Brain Behav Immun ; 68: 132-145, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29051087

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a "glove-and-stocking" distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs). In the spinal cord, activation of microglia, but not astrocyte, was persistently observed until week five after the first cisplatin injection. Additionally, mRNA levels of inflammation related molecules including IL-1ß, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD16, were increased after cisplatin treatment. Intraperitoneal (i.p.) or intrathecal (i.t.) injection with minocycline both alleviated cisplatin-induced mechanical allodynia and sensory deficits, and prevented IENFs loss. Furthermore, cisplatin enhanced triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein of 12 kDa (DAP12) signaling in the spinal cord microglia. The blockage of TREM2 by i.t. injecting anti-TREM2 neutralizing antibody significantly attenuated cisplatin-induced mechanical allodynia, sensory deficits and IENFs loss. Meanwhile, anti-TREM2 neutralizing antibody prominently suppressed the spinal IL-6, TNF-α, iNOS and CD16 mRNA level, but it dramatically up-regulated the anti-inflammatory cytokines IL-4 and IL-10. The data demonstrated that cisplatin triggered persistent activation of spinal cord microglia through strengthening TREM2/DAP12 signaling, which further resulted in CIPN. Functional blockage of TREM2 or inhibition of microglia both benefited for cisplatin-induced peripheral neuropathy. Microglial TREM2/DAP12 may serve as a potential target for CIPN intervention.


Assuntos
Glicoproteínas de Membrana/metabolismo , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/metabolismo , Receptores Imunológicos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Astrócitos/metabolismo , Cisplatino/efeitos adversos , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperalgesia/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Ativação de Macrófagos , Masculino , Glicoproteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/fisiologia , Minociclina/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Dor/metabolismo , Receptores de IgG/metabolismo , Receptores Imunológicos/fisiologia , Transdução de Sinais , Medula Espinal/patologia , Medula Espinal/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
19.
Yi Chuan ; 40(11): 1044-1047, 2018 Nov 20.
Artigo em Zh | MEDLINE | ID: mdl-30465538

RESUMO

The Genome Sequence Archive (GSA), a new data repository for raw sequence reads in China, has been developed in compliance with the International Nucleotide Sequence Database Collaboration (INSDC) standards. It supports data generated from a variety of sequencing platforms ranging from Sanger sequencing to single-cell sequencing and provides data storing and sharing services freely for worldwide scientific communities. Since it went online in late 2015, GSA has archived more than 500 TB data and been acknowledged by many high-profile journals, including Cell, Nature, PNAS, GPB, etc. Focusing on omics data submission, storing and sharing typically for Chinese users, GSA promotes the initiative of the National Bioinformatics Center of China. This paper introduces the specifies of GSA as data collection, curation, management and exchange to facilitate users to understand and use GSA database.


Assuntos
Curadoria de Dados , Bases de Dados de Ácidos Nucleicos , China , Biologia Computacional , Curadoria de Dados/métodos , Bases de Dados de Ácidos Nucleicos/instrumentação , Bases de Dados de Ácidos Nucleicos/organização & administração , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Sistemas On-Line
20.
Nucleic Acids Res ; 43(Database issue): D777-83, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25404132

RESUMO

The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼ 19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.


Assuntos
Bases de Dados de Ácidos Nucleicos , Cães/genética , Polimorfismo de Nucleotídeo Único , Lobos/genética , Animais , Genoma , Internet
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