Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
1.
Adv Sci (Weinh) ; 11(3): e2304709, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38009798

RESUMO

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.


Assuntos
Perda Auditiva , Zumbido , Humanos , Camundongos , Animais , Giro do Cíngulo/patologia , Zumbido/patologia , Proteômica , Eletroencefalografia
2.
Neuroimage ; 264: 119766, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36435344

RESUMO

Predictions, the bridge between the internal and external worlds, are established by prior experience and updated by sensory stimuli. Responses to omitted but unexpected stimuli, known as omission responses, can break the one-to-one mapping of stimulus-response and can expose predictions established by the preceding stimulus built up. While research into exogenous predictions (driven by external stimuli) is often reported, that into endogenous predictions (driven by internal percepts) is rarely available in the literature. Here, we report evidence for endogenous predictions established by the Zwicker tone illusion, a phantom pure-tone-like auditory percept following notch noises. We found that MMN, P300, and theta oscillations could be recorded using an omission paradigm in subjects who can perceive Zwicker tone illusions, but could not in those who cannot. The MMN and P300 responses relied on attention, but theta oscillations did not. In-depth analysis shows that an increase in single-trial theta power, including total and induced theta, with the endogenous prediction, is lateralized to the left frontal brain areas. Our study depicts that the brain automatically analyzes internal perception, progressively establishes predictions and yields prediction errors in the left frontal region when a violation occurs.


Assuntos
Ilusões , Humanos , Ilusões/fisiologia , Som , Atenção/fisiologia , Córtex Cerebral/fisiologia , Lobo Frontal/fisiologia , Estimulação Acústica , Percepção Auditiva/fisiologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia
3.
Mol Genet Genomic Med ; 10(11): e2039, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36052765

RESUMO

BACKGROUND: The EVEN-plus syndrome (epiphyseal-vertebral-ear-nose dysplasia plus associated findings) is an extremely rare autosomal recessive inherited disease characterised by specific facial features and skeletal dysplasia. It has a prenatal onset due to defects in the HSPA9 gene. The syndrome has not been reported previously in China. METHODS: This study reported the characteristics, examination results, diagnosis and treatment of a female case aged 3 years and 3 months. RESULTS: The patient had global developmental delay and specific facial features, including a prominent forehead, a bilateral auricle deformity, a collapsed nose, a high palatine arch, a short neck and other appearance abnormalities. Her hip joint magnetic resonance imaging (MRI) results showed bilateral femoral head epiphyseal dysplasia with a fork-shaped malformation at the distal end, and her brain MRI showed white matter myelin dysplasia. HSPA9 compound heterozygous variants c.882_c.883delAG and c.613A>G were identified by exome sequencing. CONCLUSIONS: This finding expands the spectra of EVEN-plus syndrome phenotype and pathogenic variants and suggests that c.882_c.883delAG may have a higher distribution frequency in East Asian populations.


Assuntos
Anormalidades Musculoesqueléticas , Osteocondrodisplasias , Gravidez , Feminino , Humanos , Exoma , Sequenciamento do Exoma , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Fenótipo , Anormalidades Musculoesqueléticas/genética
4.
Front Behav Neurosci ; 16: 902175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832295

RESUMO

Classical notion claims that a memory is implicit if has nothing to do with consciousness during the information retrieval from storage, or is otherwise explicit. Here, we demonstrate event-related potential evidence for involuntary consciousness during implicit memory retrieval. We designed a passive oddball paradigm for retrieval of implicit memory in which an auditory stream of Shepard tones with musical pitch interval contrasts were delivered to the subjects. These contrasts evoked a mismatch negativity response, which is an event-related potential and a neural marker of implicit memory, in the subjects with long-term musical training, but not in the subjects without. Notably, this response was followed by a salient P3 component which implies involvement of involuntary consciousness in the implicit memory retrieval. Finally, source analysis of the P3 revealed moving dipoles from the frontal lobe to the insula, a brain region closely related to conscious attention. Our study presents a case of involvement of involuntary consciousness in the implicit memory retrieval and suggests a potential challenge to the classical definition of implicit memory.

5.
Microbiol Spectr ; 10(2): e0227621, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35404086

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) infection leads to late-term reproductive failure and respiratory illness that affect the global swine industry. Epigallocatechin gallate (EGCG) is a polyphenolic compound from green tea that exerts antiviral activity against diverse viruses. This study aimed to report an uncharacterized mechanism of how EGCG restricted PRRSV proliferation. EGCG showed no significant effects on cell viability, cell cycle progression, and apoptosis in porcine alveolar macrophages and MARC-145 cells. The treatment of cells with EGCG attenuated the replication of both highly pathogenic and less pathogenic PRRSV in vitro. The viral life cycle analysis demonstrated that EGCG affected PRRSV replication and assembly, but not viral attachment, entry, or release. Interestingly, EGCG treatment abrogated the increased lipid droplets formation and lipid content induced by PRRSV infection. We further demonstrated that EGCG blocked PRRSV-stimulated expression of the key enzymes in lipid synthesis. In addition, EGCG attenuated PRRSV-induced autophagy that is critical for PRRSV proliferation. The supplementation of oleic acid restored PRRSV replication and assembly under EGCG treatment. Together, our results support that EGCG inhibits PRRSV proliferation through disturbing lipid metabolism. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-positive-stranded RNA virus that causes acute respiratory distress in piglets and reproductive failure in sows, resulting in huge economic losses to the global swine industry. Several lines of evidence have suggested the crucial roles of lipids in PRRSV proliferation. Our previous report demonstrated that PRRSV activated lipophagy to facilitate viral replication through downregulating the expression of N-Myc downstream-regulated gene 1. The manipulation of lipid metabolism may be a new perspective to prevent PRRSV spread. In the present study, we reported that epigallocatechin-3-gallate (EGCG), the major component of green tea catechins, significantly attenuated PRRSV infection through inhibiting lipid synthesis and autophagy. Given that natural products derived from plants have helped in the prevention and treatment of various infectious diseases, EGCG has a great potential to serve as a safe and environmentally friendly natural compound to treat PRRSV infection.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Catequina/análogos & derivados , Linhagem Celular , Proliferação de Células , Feminino , Metabolismo dos Lipídeos , Lipídeos , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Suínos , Chá
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1504-1509, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627431

RESUMO

OBJECTIVE: To investigate the effect of arsenic disulfide (AS2S2) combined with itraconazole on the proliferation, apoptosis and hedgehog pathway of diffuse large B-cell lymphoma (DLBCL) cells. METHODS: The human DLBCL cell OCI-LY3 was treated with different concentrations of AS2S2 and itraconazole. Cell proliferation inhibition was detected by CCK-8, cell apoptosis rate was determined by flow cytometry. The expression levels of BCL-2, BAX, SMO and GLi1 were detected by Western blot. RESULTS: The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690,r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS2S2(P<0.05). The protein levels of SMO and Glil were significantly down-regulated after treated by arsenic disulfide and itraconazole alone(P<0.01). The protein expression levels of SMO and Glil was down-regulated in the combined-treatment group(P<0.01). CONCLUSION: Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS2S2 and itraconazole show a synergistic effects, which may be related with the down-regulated protein expression of SMO and Glil of Hedgehog signaling pathway.


Assuntos
Proteínas Hedgehog , Linfoma Difuso de Grandes Células B , Apoptose , Arsenicais , Humanos , Itraconazol/farmacologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Sulfetos
7.
Mol Ther Oncolytics ; 21: 134-143, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-33981829

RESUMO

We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8+ T cells, CD4+ memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes.

8.
Genomics ; 113(3): 1272-1280, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33677058

RESUMO

Here, we present a draft genome of the tapeworm Dipylidium caninum (family Dipylidiidae) and compare it with other cestode genomes. This draft genome of D. caninum is 110 Mb in size, has a repeat content of ~13.4% and is predicted to encode ~10,000 protein-coding genes. We inferred excretory/secretory molecules (representing the secretome), other key groups of proteins (including peptidases, kinases, phosphatases, GTPases, receptors, transporters and ion-channels) and predicted potential intervention targets for future evaluation. Using 144 shared single-copy orthologous sequences, we investigated the genetic relationships of cestodes for which nuclear genomes are available. This study provides first insights into the molecular biology of D. caninum and a new resource for comparative genomic and genetic explorations of this and other flatworms.


Assuntos
Cestoides , Infecções por Cestoides , Platelmintos , Animais , Cestoides/genética , Genômica
9.
Front Hum Neurosci ; 15: 621677, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613214

RESUMO

The question of what determines brain laterality for auditory cognitive processing is unresolved. Here, we demonstrate a swap of hemisphere dominance from right to left during semantic interpretation of Chinese lexical tones in native speakers using simultaneously recorded mismatch negativity response and behavioral reaction time during dichotic listening judgment. The mismatch negativity, which is a brain wave response and indexes auditory processing at an early stage, indicated right hemisphere dominance. In contrast, the behavioral reaction time, which reflects auditory processing at a later stage, indicated a right ear listening advantage, or left hemisphere dominance. The observed swap of hemisphere dominance would not occur when the lexical tone was substituted with a meaningless pure tone. This swap reveals dependence of hemisphere labor division initially on acoustic and then on functional cues of auditory inputs in the processing from sound to meaning.

10.
Fish Shellfish Immunol ; 92: 1-10, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31141718

RESUMO

Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species of hydrothermal vent communities, which inside its gill chamber harbors ectosymbioses with taxonomic invariability while compositional flexibility. Several studies have revealed that the establishment of symbiosis can be initiated and selected by innate immunity-related pattern recognition receptors (PRRs), such as C-type lectins (CTLs). In this research, a CTL was identified in R. exoculata (termed RCTL), which showed high expression at both mRNA and protein levels in the scaphognathite, an organ where the ectosymbionts are attached outside its setae. Linear correlationships were observed between the relative quantities of two major symbionts and the expression of RCTL based on analyzing different shrimp individuals. The recombinant protein of RCTL could recognize and agglutinate the cultivable γ-proteobacterium of Escherichia coli in a Ca2+-dependent manner, obeying a dose-dependent and time-cumulative pattern. Unlike conventional crustacean CTLs, the involvement of RCTL could not affect the bacterial growth, which is a key issue for the successful establishment of symbiosis. These results implied that RCTL might play a critical role in symbiotic recognition and attachment to R. exoculata. It also provides insights to understand how R. exoculata adapted to such a chemosynthesis-based environment.


Assuntos
Decápodes/genética , Decápodes/imunologia , Imunidade Inata/genética , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Escherichia coli/fisiologia , Perfilação da Expressão Gênica , Lectinas Tipo C/química , Filogenia , Alinhamento de Sequência , Simbiose
11.
Zhongguo Zhong Yao Za Zhi ; 44(6): 1220-1226, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989987

RESUMO

The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study,a total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride group,and low,medium,and high dose baicalin groups,with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group(0.07 g·L~(-1))and the low(3.33 g·L~(-1)),medium(6.67 g·L~(-1)),and high dose(10 g·L~(-1))baicalin groups received corresponding drugs by gavage administration according to the body weight(0.015 m L·g~(-1)),while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks,twice a day.The body weight of the rats and the amount of remaining feed were weighed daily,and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods,respectively.RESULTS: showed that baicalin did not affect the normal eating and weight gain of rats,and the weight gain of rats was even more significant than that in the normal group(P<0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes,the expression of both proteins in each drug-administered group was higher than that in the model group(P<0.05);besides,the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group(P<0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats(P<0.05).In conclusion,baicalin does not affect the normal growth and development of SHR rats,so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein,and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Animais , Modelos Animais de Doenças , Flavonoides , Peptídeos e Proteínas de Sinalização Intracelular , Sistema de Sinalização das MAP Quinases , Proteínas Serina-Treonina Quinases , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
12.
World Neurosurg ; 126: e688-e693, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30844532

RESUMO

OBJECTIVE: Neurorrhaphy with interpositional graft is a practical technique to achieve facial reanimation when the continuity of the facial nerve is interrupted and a large gap between the proximal and distal stump exists. The aim of this study was to report long-term outcomes of neurorrhaphy for facial reanimation with interpositional graft. The roles of some variable factors in the outcome of neurorrhaphy with interpositional graft were also evaluated and compared. METHODS: A retrospective case series from a single tertiary referral center comprised 23 patients with facial nerve interruptions who underwent neurorrhaphy with interpositional graft using either end-to-end anastomosis or end-to-side hypoglossal-facial technique. Preoperative data (age, sex, primary lesion, interval from paralysis to surgery, facial nerve function), intraoperative data (surgical approach, graft and type of neurorrhaphy), and postoperative data (facial nerve function) were collected and analyzed. RESULTS: Mean follow-up time was 26.6 ± 11.9 months. Patients who underwent neurorrhaphy for facial reanimation within 1 year after onset of facial paralysis were more likely to achieve House-Brackmann grade ≤3 compared with patients who underwent neurorrhaphy >1 year after onset of facial paralysis (odds ratio = 23.85, P = 0.04). No other factors were associated with improved outcomes. CONCLUSIONS: Early neurorrhaphy with interpositional graft (≤1 year) for facial reanimation resulted in better final facial nerve function outcomes compared with a delayed procedure.


Assuntos
Traumatismos do Nervo Facial/cirurgia , Nervo Facial/cirurgia , Paralisia Facial/cirurgia , Nervo Hipoglosso/transplante , Transferência de Nervo/métodos , Adulto , Traumatismos do Nervo Facial/complicações , Paralisia Facial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem
13.
Biometals ; 32(2): 251-264, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30756217

RESUMO

Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species among hydrothermal vent communities along the Mid-Atlantic Ridge. This shrimp can tolerate high concentrations of heavy metals such as iron, but the mechanisms used for detoxification and utilization of excess metals remain largely unknown. Ferritin is a major iron storage protein in most living organisms. The central heavy subunit of ferritin (H-ferritin) possesses ferroxidase activity and converts iron from Fe2+ to Fe3+, the non-toxic form used for storage. In the present study, the H-ferritin RexFrtH was identified in the hydrothermal vent shrimp R. exoculata, and found to be highly expressed in the gill, the main organ involved in bioaccumulation of metals, at both RNA and protein levels. Accumulation of RexFrtH decreased from efferent to afferent vessels, coinciding with the direction of water flow through the gills. Fe3+ was localized with RexFrtH, and in vitro iron-binding and ferroxidase assays using recombinant RexFrtH confirmed the high affinity for iron. Based on these results, we propose a model of iron metabolism in R. exoculata gills; ferrous iron from ambient hydrothermal water accumulates and is converted and stored in ferric form by RexFrtH as an iron reservoir when needed for metabolism, or excreted as an intermediate to prevent iron overload. The findings expand our understanding of the adaptation strategies used by shrimps inhabiting extreme hydrothermal vents to cope with extremely high heavy metal concentrations.


Assuntos
Apoferritinas/metabolismo , Decápodes/metabolismo , Fontes Hidrotermais , Ferro/metabolismo , Animais
14.
J Zhejiang Univ Sci B ; 20(2): 131-145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30112880

RESUMO

Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-ß superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.


Assuntos
Proteínas Morfogenéticas Ósseas/fisiologia , Orelha Interna/embriologia , Padronização Corporal , Receptores de Proteínas Morfogenéticas Ósseas/fisiologia , Diferenciação Celular , Cóclea/embriologia , Proteínas Hedgehog/fisiologia , Humanos , Transdução de Sinais/fisiologia , Proteínas Smad/fisiologia , Vestíbulo do Labirinto/embriologia , Via de Sinalização Wnt
15.
Asia Pac J Clin Oncol ; 14(2): e81-e87, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29071806

RESUMO

BACKGROUND: Currently, amrubicin is used as first-line in the treatment of patients with small-cell lung cancer (SCLC). However, the effect of amrubicin-based treatment in extensive-disease (ED) SCLC remains controversial. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of amrubicin-based regimen in the treatment of patients with ED-SCLC. METHODS: RCTs published in PubMed, Web of Science, Embase, and ClinicalTrials.gov were systematically reviewed. Eligible studies were these that evaluated the efficacy and safety profiles of amrubicin-based regimen in ED-SCLC. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and adverse events. Results were expressed with hazard ratio (HR) with 95% confidence intervals (CIs), and risk ratio (RR) with 95% CIs. RESULTS: Four RCTs involving a total of 740 patients met the inclusion criteria and were included in this meta-analysis. Amrubicin-based regimen was not associated with significantly prolonged PFS (HR = 1.07, 95% CI: 0.90-1.30; P = 0.463) and OS (HR = 1.07, 95% CI: 0.89-1.29; P = 0.443) in patients with ED-SCLC. However, it significantly improved ORR (RR = 1.14, 95% CI: 1.04-1.25; P = 0.008). Subgroup analysis demonstrated that neither amrubicin alone nor in combination with cisplatin prolonged the PFS and OS, and only the combination therapy significantly increased ORR. The incidence of grade ≥3 adverse events was comparable between amrubicin-containing and other treatment groups (RR = 1.42, 95% CI: 0.78-2.58; P = 0.248). However, amrubicin-based treatment induced a significantly higher incidence of febrile neutropenia (RR = 3.32, 95% CI: 2.04-5.41; P < 0.001), anemia (RR = 1.44, 95% CI: 1.06-1.97; P = 0.022), leukopenia (RR = 2.17, 95% CI: 1.41-3.33; P < 0.001), neutropenia (RR = 1.33, 95% CI: 1.04-1.70; P = 0.021), and interstitial lung disease (RR = 1.58, 95% CI: 1.21-1.98; P < 0.001). CONCLUSION: Amrubicin-based regimen used as first-line had no survival benefits in patients with ED-SCLC. But it significantly improved ORR. Further well-conducted, large-scale trials are needed to validate these findings.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Antraciclinas/administração & dosagem , Antraciclinas/farmacologia , Antineoplásicos/farmacologia , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/patologia , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Pequenas Células do Pulmão/patologia
16.
Sci Rep ; 7(1): 11648, 2017 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-28912500

RESUMO

Gallid alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek's disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the 'Cornell Model' description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology.


Assuntos
Doença de Marek/genética , Doença de Marek/virologia , Baço/metabolismo , Baço/virologia , Transcriptoma , Animais , Análise por Conglomerados , Biologia Computacional/métodos , Progressão da Doença , Perfilação da Expressão Gênica , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Doença de Marek/metabolismo , Doença de Marek/patologia , Mapeamento de Interação de Proteínas , Reprodutibilidade dos Testes , Transdução de Sinais , Baço/patologia
17.
Mol Cell Biol ; 37(7)2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28031330

RESUMO

As a prominent characteristic of cell life, the regulation of cell quiescence is important for proper development, regeneration, and stress resistance and may play a role in certain degenerative diseases. However, the mechanism underlying quiescence remains largely unknown. Encysted embryos of Artemia are useful for studying the regulation of this state because they remain quiescent for prolonged periods during diapause, a state of obligate dormancy. In the present study, SET domain-containing protein 4, a histone lysine methyltransferase from Artemia, was identified, characterized, and named Ar-SETD4. We found that Ar-SETD4 was expressed abundantly in Artemia diapause embryos, in which cells were in a quiescent state. Meanwhile, trimethylated histone H4K20 (H4K20me3) was enriched in diapause embryos. The knockdown of Ar-SETD4 reduced the level of H4K20me3 significantly and prevented the formation of diapause embryos in which neither the cell cycle nor embryogenesis ceased. The catalytic activity of Ar-SETD4 on H4K20me3 was confirmed by an in vitro histone methyltransferase (HMT) assay and overexpression in cell lines. This study provides insights into the function of SETD4 and the mechanism of cell quiescence regulation.


Assuntos
Artemia/embriologia , Artemia/metabolismo , Biocatálise , Ciclo Celular , Diapausa de Inseto , Histonas/metabolismo , Lisina/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Artemia/citologia , Sequência de Bases , Divisão Celular , Linhagem Celular Tumoral , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Técnicas de Silenciamento de Genes , Metilação , Fatores de Transcrição/química , Fatores de Transcrição/genética
18.
Sci Rep ; 6: 37224, 2016 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-27917879

RESUMO

The gut harbours diverse and complex microbiota, which influence body health including nutrient metabolism, immune development, and protection from pathogens. Pregnancy is associated with immune and metabolic changes that might be related to microbiota compositional dynamics. We therefore investigated the colonic luminal bacteria community in Huanjiang mini-pigs fed diets with different nutrient levels from the first to third trimester of pregnancy. The concentrations of intestinal metabolites including short-chain fat acids, NH3-N, indole, skatole, and bioamines were also determined. We found that the colonic bacteria species richness estimators (Chao1 and ACE) decreased with increased gestational age. The dominant phyla identified were Firmicutes and Bacteroidetes; the dominant genera were Lactobacillus, Treponema, Ruminococcus, Clostridium, and Prevotella. In addition, microbiota displayed spatial and temporal heterogeneity in composition, diversity, and species abundance in different colonic segments from the first to third trimester of pregnancy. Furthermore, the bacterial metabolites also changed according to the diet used and the pregnancy stage. These findings suggest that colonic bacteria richness decreased as gestational age increased, and that the higher nutrient level diet increased the production of metabolites related to nitrogen metabolism. However, although the higher nutrient diet was associated with pregnancy syndrome, causal links remain to be determined.


Assuntos
Ração Animal , Colo/microbiologia , Microbioma Gastrointestinal , Animais , Aminas Biogênicas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal/genética , Indóis/metabolismo , Nitrogênio/metabolismo , Gravidez , Escatol/metabolismo , Suínos , Porco Miniatura
19.
Stress ; 19(6): 609-620, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27696924

RESUMO

The most widespread type of RNA editing, conversion of adenosine to inosine (A→I), is catalyzed by two members of the adenosine deaminase acting on RNA (ADAR) family, ADAR1 and ADAR2. These enzymes edit transcripts for neurotransmitter receptors and ion channels during adaption to changes in the physical environment. In the primitive crustacean Artemia, when maternal adults are exposed to unfavorable conditions, they release diapause embryos to withstand harsh environments. The aim of the current study was therefore to elucidate the role of ADAR of Artemia diapause embryos in resistance to stress. Here, we identified Artemia ADAR (Ar-ADAR), which harbors a putative nuclear localization sequence (NLS) and two double-stranded RNA-binding motifs (dsRBMs) in the amino-terminal region and an adenosine deaminase (AD) domain in the carboxyl-terminal region. Western blot and immunofluorescence analysis revealed that Ar-ADAR is expressed abundantly in post-diapause embryos. Artemia (n = 200, three replicates) were tested under basal and stress conditions. We found that Ar-ADAR was significantly induced in response to the stresses of salinity and heat-shock. Furthermore, in vivo knockdown of Ar-ADAR (n = 100, three replicates) by RNA interference induced formation of pseudo-diapause embryos, which lack resistance to the stresses and exhibit high levels of apoptosis. These results indicate that Ar-ADAR contributes to resistance to stress in Artemia diapause embryos.


Assuntos
Adenosina Desaminase/genética , Artemia/genética , Edição de RNA/genética , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Animais , Apoptose/genética , Sequência de Bases , Biologia Computacional , Diapausa , Embrião não Mamífero , Técnicas de Silenciamento de Genes , Sinais de Localização Nuclear , Interferência de RNA , RNA de Cadeia Dupla/genética
20.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(5): 3115-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-25665594

RESUMO

In this study we completely determined and analyzed the mitochondrial genome of the Mid-Atlantic Ridge hydrothermal-vent shrimp Rimicaris exoculata (Crustacea: Decapoda: Alvinocarididae). The circular molecule is 15,902 bp in size with an AT content of 65.7%, composed of the same 37 mitochondrial genes as in all other known metazoan mitogenomes. Sequence composition of the R. exoculata mitogenome is exceptionally similar to that of its Indian-Ocean congener R. kairei, which suggests the fact that they might diverge at a quite recent age. The genome exhibits an ancestral pancrustacean arrangement of mitochondrial genes that presents only the translocation/inversion of trnL-UUR from the ancestral arthropod pattern. Determination of the R. exoculata mitogenome can help to resolve the consensus Decapoda tree of life. It also provides more genetic information available for phylogenetics as well as population genetics on this extensively studied species from hydrothermal vents.


Assuntos
Decápodes/classificação , Decápodes/genética , Genoma Mitocondrial , Animais , Composição de Bases , Ordem dos Genes , Genes Mitocondriais , Genética Populacional , Tamanho do Genoma , Fases de Leitura Aberta , Filogenia , Análise de Sequência de DNA , Sequenciamento Completo do Genoma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...