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1.
Biomolecules ; 11(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34827605

RESUMO

The subcellular locations of proteins are closely related to their functions. In the past few decades, the application of machine learning algorithms to predict protein subcellular locations has been an important topic in proteomics. However, most studies in this field used only amino acid sequences as the data source. Only a few works focused on other protein data types. For example, three-dimensional structures, which contain far more functional protein information than sequences, remain to be explored. In this work, we extracted various handcrafted features to describe the protein structures from physical, chemical, and topological aspects, as well as the learned features obtained by deep neural networks. We then used these features to classify the protein subcellular locations. Our experimental results demonstrated that some of these structural features have a certain effect on the protein location classification, and can help improve the performance of sequence-based location predictors. Our method provides a new view for the analysis of protein spatial distribution, and is anticipated to be used in revealing the relationships between protein structures and functions.

2.
Front Biosci (Landmark Ed) ; 26(10): 799-812, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34719207

RESUMO

Objective: Nucleus pulposus cells (NPCs) are cells extracted from the intervertebral disc and are important for research into intervertebral disc degeneration (IVDD). NPCs live in an avascular and relatively hypoxic environment. Cobalt chloride (CoCl2) has been used in many cell studies to mimic hypoxia. The objective of this study was to explore the possibility of using CoCl2 to induce mimetic-hypoxia for NPCs and the comparison with hypoxia (1% O2) in vitro. Materials and methods: Rat nucleus pulposus cells of Passage 3-5 were used in this research. Cell viability, rate of cell apoptosis, ROS (reactive oxygen species) generation, cell migration, extracellular pH and extracellular matrix metabolism were determined to compare the influence of hypoxia (1% O2) and CoCl2 on NPCs. Results: We found that the effects of CoCl2 on NPCs was dose-dependent. At the proper concentration, CoCl2 could be used to elicit chemical hypoxia for nucleus pulposus cells in vitro and many biological effects, analogous to physical hypoxia (1% O2), could be achieved such as enhanced cell viability, decreased apoptosis and activated extracellular matrix metabolism. On the other hand, CoCl2 mimetic-hypoxia did not affect NPCs glycolysis and migration compared to physical hypoxia. In addition, high concentration of CoCl2 (>200 µM) is harmful to NPCs with high rates of apoptosis and ECM (extracellular matrix) degradation. Conclusions: It is feasible and convenient to use CoCl2 to induce chemical mimetic hypoxia for culturing NPCs on the premise of appropriate concentration. But in aspects of cell migration and glycolysis, CoCl2 could not achieve similar results with physical hypoxia. This study may provide a convenient method and enlightenment to induce mimetic-hypoxia for researchers studying NPCs and IVVD.

3.
Appl Opt ; 60(28): 8809-8817, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613107

RESUMO

To reduce the impact of the image reconstruction process and improve the identification efficiency of the multislit streak tube imaging lidar (MS-STIL) system, an object classification method based on the echo of the MS-STIL system is proposed. A streak image data set is constructed that contains a total of 240 common outdoor targets in 6 categories. Additionally, the deep-learning network model based on ResNet is chosen to implement streak image classification. The effects of two classification methods based on streak images and reconstructed depth images are compared. To verify the maximum classification capability of the proposed method, the recognition effects are investigated under 6 and 20 classes. The results show that the classification accuracy decreases from 99.42% to 67.64%. After the data set is expanded, the classification accuracy improved to 85.35% when the class number of the target is 20.

4.
Nanomaterials (Basel) ; 11(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34578669

RESUMO

Martensite transformation and grain refinement can make austenitic stainless steel stronger, but this comes at a dramatic loss of both ductility and corrosion resistance. Here we report a novel gradient structure in 301 stainless steel sheets, which enables an unprecedented combination of high strength, improved ductility and good corrosion resistance. After producing inter-layer microstructure gradient by surface mechanical attrition treatment, the sheet was annealed at high temperature for a short duration, during which partial reverse transformation occurred to form recrystallized austenitic nano-grains in the surface layer, i.e., introducing extra intra-layer heterogeneity. Such 3D microstructure heterogeneity activates inter-layer and inter-phase interactions during deformation, thereby producing back stress for high yield strength and hetero-deformation induced (HDI) hardening for high ductility. Importantly, the recrystallized austenitic nano-grains significantly ameliorates the corrosion resistance. These findings suggest an effective route for evading the strength-ductility and strength-corrosion tradeoffs in stainless steels simultaneously.

5.
Nat Commun ; 12(1): 4880, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385444

RESUMO

Accurate and imperceptible monitoring of electrophysiological signals is of primary importance for wearable healthcare. Stiff and bulky pregelled electrodes are now commonly used in clinical diagnosis, causing severe discomfort to users for long-time using as well as artifact signals in motion. Here, we report a ~100 nm ultra-thin dry epidermal electrode that is able to conformably adhere to skin and accurately measure electrophysiological signals. It showed low sheet resistance (~24 Ω/sq, 4142 S/cm), high transparency, and mechano-electrical stability. The enhanced optoelectronic performance was due to the synergistic effect between graphene and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), which induced a high degree of molecular ordering on PEDOT and charge transfer on graphene by strong π-π interaction. Together with ultra-thin nature, this dry epidermal electrode is able to accurately monitor electrophysiological signals such as facial skin and brain activity with low-motion artifact, enabling human-machine interfacing and long-time mental/physical health monitoring.


Assuntos
Eletrodos , Eletrofisiologia/métodos , Epiderme/fisiologia , Desenho de Equipamento/métodos , Monitorização Fisiológica/métodos , Dispositivos Eletrônicos Vestíveis , Artefatos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Condutividade Elétrica , Eletrofisiologia/instrumentação , Eletrofisiologia/normas , Desenho de Equipamento/normas , Grafite/química , Humanos , Estrutura Molecular , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/normas , Movimento (Física) , Polímeros/química , Poliestirenos/química , Pele
6.
Endocr Connect ; 10(9): 980-994, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34319906

RESUMO

Insulin-like growth factor 1 (IGF1), also known as somatomedin C, is essential for the regulation of animal growth and development. In many species, the IGF1 gene can be alternatively spliced into multiple transcripts, encoding different pre-pro-IGF1 proteins. However, the exact alternative splicing patterns of IGF1 and the sequence information of different splice variants in sheep are still unclear. In this study, four splice variants (class 1-Ea, class 1-Eb, class 2-Ea, and class 2-Eb) were obtained, but no IGF1 Ec, similar to that found in other species, was discovered. Bioinformatics analysis showed that the four splice variants shared the same mature peptide (70 amino acids) and possessed distinct signal peptides and E peptides. Tissue expression analysis indicated that the four splice variants were broadly expressed in all tested tissues and were most abundantly expressed in the liver. In most tissues and stages, the expression of class 1-Ea was highest, and the expression of other splice variants was low. Overall, levels of the four IGF1 splice variants at the fetal and lamb stages were higher than those at the adult stage. Overexpression of the four splice variants significantly increased fibroblast proliferation and inhibited apoptosis (P < 0.05). In contrast, silencing IGF1 Ea or IGF1 Eb with siRNA significantly inhibited proliferation and promoted apoptosis (P < 0.05). Among the four splice variants, class 1-Ea had a more evident effect on cell proliferation and apoptosis. In summary, the four ovine IGF1 splice variants have different structures and expression patterns and might have different biological functions.

7.
J Vis Exp ; (172)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34279508

RESUMO

Endosomal trafficking is an essential cellular process that regulates a broad range of biological events. Proteins are internalized from the plasma membrane and then transported to the early endosomes. The internalized proteins could be transited to the lysosome for degradation or recycled back to the plasma membrane. A robust endocytic recycling pathway is required to balance the removal of membrane materials from endocytosis. Various proteins are reported to regulate the pathway, including ADP-ribosylation factor 6 (ARF6). Density gradient ultracentrifugation is a classical method for cell fractionation. After the centrifugation, organelles are sedimented at their isopycnic surface. The fractions are collected and used for other downstream applications. Described here is a protocol to obtain a recycling endosome-containing fraction from transfected mammalian cells using density gradient ultracentrifugation. The isolated fractions were subjected to standard Western blotting for analyzing their protein contents. By employing this method, we identified that the plasma membrane targeting of engulfment and cell motility 1 (ELMO1), a Ras-related C3 botulinum toxin substrate 1 (Rac1) guanine nucleotide exchange factor, is through ARF6-mediated endocytic recycling.


Assuntos
Endocitose , Endossomos , Animais , Membrana Celular/metabolismo , Endossomos/metabolismo , Transporte Proteico , Ultracentrifugação
8.
World J Clin Cases ; 9(16): 3796-3813, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34141737

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading at an alarming rate, and it has created an unprecedented health emergency threatening tens of millions of people worldwide. Previous studies have indicated that SARS-CoV-2 ribonucleic acid could be detected in the feces of patients even after smear-negative respiratory samples. However, demonstration of confirmed fecal-oral transmission has been difficult. Clinical studies have shown an incidence rate of gastrointestinal (GI) symptoms ranging from 2% to 79.1% in patients with COVID-19. They may precede or accompany respiratory symptoms. The most common GI symptoms included nausea, diarrhea, and abdominal pain. In addition, some patients also had liver injury, pancreatic damage, and even acute mesenteric ischemia/thrombosis. Although the incidence rates reported in different centers were quite different, the digestive system was the clinical component of the COVID-19 section. Studies have shown that angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, was not only expressed in the lungs, but also in the upper esophagus, small intestine, liver, and colon. The possible mechanism of GI symptoms in COVID-19 patients may include direct viral invasion into target cells, dysregulation of angiotensin-converting enzyme 2, immune-mediated tissue injury, and gut dysbiosis caused by microbiota. Additionally, numerous experiences, guidelines, recommendations, and position statements were published or released by different organizations and societies worldwide to optimize the management practice of outpatients, inpatients, and endoscopy in the era of COVID-19. In this review, based on our previous work and relevant literature, we mainly discuss potential fecal-oral transmission, GI manifestations, abdominal imaging findings, relevant pathophysiological mechanisms, and infection control and prevention measures in the time of COVID-19.

9.
J Agric Food Chem ; 69(25): 7016-7027, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34060828

RESUMO

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha (kucha), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis. This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.


Assuntos
Alcaloides , Camellia sinensis , Animais , Antidepressivos , Fator Neurotrófico Derivado do Encéfalo/genética , China , Depressão/tratamento farmacológico , Hipocampo , Camundongos , Neurogênese , Purinas , Ratos , Estresse Psicológico , Chá , Ácido Úrico/análogos & derivados
10.
PeerJ ; 9: e10922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954024

RESUMO

Background: Quercus liaotungensis Koidz. is an ecologically and economically important tree species widely distributed in Northern China. However, the effective assessment, utilization, and protection of Q. liaotungensis resources remain unexplored. Methods: In total, 120 samples obtained from 12 Q. liaotungensis populations of Northern China were investigated for genetic diversity and structure using 19 simple sequence repeat (SSR) primer pairs. Results: The total number of alleles detected was 293, the average number of effective allele (Ne) was 6.084, the genetic differentiation coefficient (Fst) was 0.033, and the mean observed heterozygosity (Ho) and expected heterozygosity (He) were 0.690 and 0.801, respectively. Moreover, analysis of molecular variance (AMOVA) showed a 5.5% genetic variation among 12 Q. liaotungensis populations, indicating that a high level of genetic diversity and a low degree of genetic differentiation among Q. liaotungensis populations. STRUCTURE and cluster analysis divided the 12 Q. liaotungensis populations into the following three subpopulations: Bashang Plateau subpopulation (SH), Liaodong Peninsula subpopulation (NC), and Loess Plateau subpopulation (other 10 populations). The cluster analysis based on 19 climatic factors was consistent with the genetic structure. A positive correlation was found between genetic distance and geographical distance (r = 0.638, p = 0.028) by the Mantel test, and two boundaries were found among the 12 Q. liaotungensis populations by the Barrier analysis, indicating that Q. liaotungensis populations existed isolated by geographical distance and physical barrier. Conclusion: This study suggests that geographical isolation, physical barrier, climatic types, and natural hybridization promote the formation of genetic structures, which can contribute to future protection and genetic improvement of Q. liaotungensis.

11.
Cereb Cortex ; 31(9): 4398-4410, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-33895811

RESUMO

While social interaction between a mother and her child has been found to play an important role in the child's committed compliance, the underlying neurocognitive process remains unclear. To investigate this process, we simultaneously recorded and assessed brain activity in 7-year-old children and in children's mothers or strangers during a free-play task using functional near-infrared spectroscopy-based hyperscanning. The results showed that a child's committed compliance was positively associated with the child's responsiveness but was negatively associated with mutual responsiveness and was not associated with the mother's responsiveness during mother-child interactions. Moreover, interpersonal neural synchronization (INS) at the temporoparietal junction mediated the relationship between the child's responsiveness and the child's committed compliance during mother-child interactions when the child's brain activity lagged behind that of the mother. However, these effects were not found during stranger-child interactions, nor were there significant effects in the mother-child pair when no real interactions occurred. Finally, we found a transfer effect of a child's committed compliance from mother-child interactions to stranger-child interactions via the mediation of mother-child INS, but the opposite did not occur. Together, these findings suggest that a child's responsiveness during mother-child interactions can significantly facilitate her or his committed compliance by increasing mother-child INS.

12.
Phytomedicine ; 85: 153514, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33676083

RESUMO

BACKGROUND: Prostate cancer (PCa) is a major cause of morbidity and mortality in men in both developed and developing countries. Androgens and the androgen receptor (AR) play predominant roles in the progression of PCa. Neoisoliquiritin (NEO) belongs to the class of licorice (Glycyrrhiza) flavonoids, which have a variety of biological activities including anti-depressant, anti-tumor-promoting, and anti-inflammation properties. Licorice root has cancer chemopreventive effects and has been given to PCa patients as an ingredient of PC-SPES, a commercially available combination of eight herbs. Therefore, we determined if NEO can suppress the proliferation of PCa cells. PURPOSE: We investigated whether and how NEO exerts its anti-neoplastic activity against PCa. METHODS: The Cell Counting Kit 8 and flow cytometry were used to evaluate the effects of NEO on the proliferation and cell cycle progression of AR-dependent (LNCaP) and AR-independent (PC3) PCa cells. RNA sequencing was employed to examine the genome-wide changes in responsiveness to NEO in LNCaP cells. Quantitative PCR, Western blotting, docking, chromatin immunoprecipitation, and dual-luciferase reporter assays were conducted to determine the mechanism of action of NEO and its potential cross-talk with AR. A LNCaP xenograft nude mouse model was used to determine the inhibitory effects of NEO on AR-dependent PCa tumors in vivo. RESULTS: NEO inhibited LNCaP cell proliferation in vitro by inducing G0/G1 phase cell cycle arrest. Conversely, NEO treatment had no effect on PC3 cells. Transcriptomic analysis indicated that AR signaling might be the key target of NEO in preventing PCa. NEO regulated AR-mediated cell growth suppression and AR-sensitized cell cycle arrest in LNCaP cells. NEO also blocked several key steps in the AR signaling pathway, including proposed targeting to the ligand binding pocket of AR by computer modeling, modulating AR-androgen response element DNA-binding activity, inhibiting the expression and transcriptional activity of AR, and suppressing downstream AR signaling. CONCLUSIONS: NEO negatively regulates AR expression and activity, thus supporting the tumor suppressive role for NEO in AR-dependent PCa.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Chalcona/análogos & derivados , Glucosídeos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/metabolismo , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalcona/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Células PC-3 , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nat Chem Biol ; 17(4): 465-476, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542532

RESUMO

Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to the accumulation of 15-hydroperoxy (Hp)-arachidonoyl-phosphatidylethanolamine (15-HpETE-PE), generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, phosphatidylethanolamine (PE)-binding protein (PEBP)1. As the Ca2+-independent phospholipase A2ß (iPLA2ß, PLA2G6 or PNPLA9 gene) can preferentially hydrolyze peroxidized phospholipids, it may eliminate the ferroptotic 15-HpETE-PE death signal. Here, we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA2ß averts ferroptosis, whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6 mutations relate to neurodegeneration, we examined fibroblasts from a patient with a Parkinson's disease (PD)-associated mutation (fPDR747W) and found selectively decreased 15-HpETE-PE-hydrolyzing activity, 15-HpETE-PE accumulation and elevated sensitivity to ferroptosis. CRISPR-Cas9-engineered Pnpla9R748W/R748W mice exhibited progressive parkinsonian motor deficits and 15-HpETE-PE accumulation. Elevated 15-HpETE-PE levels were also detected in midbrains of rotenone-infused parkinsonian rats and α-synuclein-mutant SncaA53T mice, with decreased iPLA2ß expression and a PD-relevant phenotype. Thus, iPLA2ß is a new ferroptosis regulator, and its mutations may be implicated in PD pathogenesis.


Assuntos
Ferroptose/fisiologia , Fosfolipases A2 do Grupo VI/metabolismo , Animais , Araquidonato 15-Lipoxigenase/metabolismo , Modelos Animais de Doenças , Feminino , Fosfolipases A2 do Grupo VI/fisiologia , Humanos , Ferro/metabolismo , Leucotrienos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Peróxidos Lipídicos/metabolismo , Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Doença de Parkinson/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Fosfolipases/metabolismo , Fosfolipídeos/metabolismo , Ratos , Ratos Endogâmicos Lew
14.
Clin Endocrinol (Oxf) ; 95(1): 187-196, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33556187

RESUMO

PURPOSE: To compare the effectiveness and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) for the treatment of benign thyroid nodules (BTNs). METHODS: PubMed, Embase and Cochrane databases were searched up to September 11, 2020. Volume reduction rate (VRR), symptomatic and cosmetic scores analysed by standardized mean difference (SMD), and complications analysed by risk difference (RD) were performed to evaluate the efficacy and safety of RFA and MWA for treating BTNs. RESULTS: Five eligible studies were included. 899 patients with 956 BTNs and 869 patients with 938 BTNs received RFA and MWA, respectively. RFA and MWA have the similar pooled 3-month (56.0% vs. 53.9%, p = .668) and 6-month (80.8% vs. 74.9%, p = .080) VRRs. But RFA showed a significantly higher VRR than MWA after 12 months (86.2% vs. 80.0%, p = .036). The pooled symptomatic and cosmetic scores decreased significantly after 6 and 12 months in both RFA and MWA. The improvements of symptoms were equivalent between two groups at 6 (SMD: 1.17 vs. 1.12, p = .930) and 12 (SMD: 1.46 vs. 1.45, p = .930) months. No significant differences in cosmetic scores were found between two groups at 6 (SMD: 0.87 vs. 0.94, p = 0. 334) and 12 (SMD: 1.21 vs. 1.15, p = 0. 872) months. Major (RD = -0.02, P = .107) and minor (RD = 0.00, p = .661) complications did not significantly differ between RFA and MWA. CONCLUSIONS: RFA and MWA are effective and safe treatment modalities for BTNs. But RFA showed a superior 12-month VRR. RFA may have a better long-term effect on volume reduction of nodules compared with MWA.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Humanos , Micro-Ondas , Estudos Retrospectivos , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento
15.
Ann Palliat Med ; 10(1): 312-322, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545766

RESUMO

BACKGROUND: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model. METHODS: The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining. RESULTS: The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib. CONCLUSIONS: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.


Assuntos
Lesões Encefálicas , Quinolinas , Animais , Encéfalo/metabolismo , Indóis , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Life Sci ; 270: 119061, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33454364

RESUMO

For patients with hepatocellular carcinoma (HCC), early detection is critical to improve survival. Secreted frizzled-related protein 2 (SFRP2) is a candidate tumor suppressor as Wnt antagonist and SFRP2 promoter has been found hypermethylated in various malignancies. This study aimed to investigate the methylation status of SFRP2 promoter in hepatitis B virus (HBV) associated HCC and estimate its diagnostic value as a non-invasive biomarker. A total of 293 patients, including 132 patients with HBV-associated HCC, 121 with chronic hepatitis B (CHB) and 40 healthy controls (HCs) were enrolled. SFRP2 methylation level in peripheral mononuclear cells (PBMCs) was quantitatively detected by MethyLight. SFRP2 methylation level was significantly higher in patients with HBV-associated HCC than in those with CHB (p < 0.001) and HCs (p < 0.001) while mRNA level of SFRP2 was significantly lower in HCC group than the other two groups (p < 0.05). In HCC subgroup, SFRP2 methylation level markedly increased in patients >50 years old, female, with negative HBeAg, negative HBV-DNA and poor differentiation compared with the remaining groups (P < 0.05). Furthermore, SFRP2 methylation level showed a significantly better diagnostic value than alpha-fetoprotein (AFP) and the combination of AFP and methylation levels of SFRP2 markedly improved the area under the receiver operating characteristic curve (p < 0.05). In conclusion, hypermethylation of SFRP2 promoter exists in HBV-associated HCC. The combination of SFRP2 methylation level in PBMCs and AFP could significantly improve the diagnostic ability of AFP in discriminating HBV-associated HCC from CHB and SFRP2 methylation level had the potential to serve as a non-invasive biomarker for HCC diagnosis.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Membrana/genética , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Metilação de DNA/genética , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , RNA Mensageiro/metabolismo , alfa-Fetoproteínas/genética
17.
Cereb Cortex ; 31(3): 1647-1659, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33145593

RESUMO

Interpersonal touch plays a key role in creating and maintaining affiliative pair bonds in romantic love. However, the neurocognitive mechanism of interpersonal touch in affiliative pair bonding remains unclear. Here, we hypothesized that interpersonal neural synchronization (INS) during interpersonal touch underlies affiliative pair bonding between romantic couples. To test this hypothesis, INS between heterosexual romantic couples and between opposite-sex friends was measured using functional near-infrared spectroscopy-based hyperscanning, while the pairs of participants touched or vocally communicated with each other. The results showed significantly greater INS between the mentalizing and sensorimotor neural systems of two members of a pair during interpersonal touch than during vocal communication between romantic couples but not between friends. Moreover, touch-induced INS was significantly correlated with the self-reported strength of romantic love. Finally, the results also showed that men's empathy positively modulated the association between touch-induced INS increase and the strength of romantic love. These findings support the idea that INS during interpersonal touch underlies affiliative pair bonding between romantic couples and suggest that empathy plays a modulatory role in the neurocognitive mechanism of interpersonal touch in affiliative pair bonding.

18.
Environ Toxicol ; 36(2): 276-286, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33030807

RESUMO

Quinalizarin (Quina) is one of the main components of many herbal medicines and has good anti-tumor activity. However, the exact mode of cytotoxic action and signaling pathways on Quina in human esophageal cancer has not yet been confirmed. In this study, we explored the anticancer effect of Quina against human esophageal cancer HCE-4 cells and the underlying mechanisms. The results of the Cell Counting Kit-8 (CCK-8) assay showed that Quina inhibited the viability of human esophageal cancer HCE-4 cells in a dose-dependent and time-dependent manner. It also inhibited HCE-4 cells proliferation and induced apoptosis by increasing the levels of Bad, caspase-3, and PARP, decreasing the level of Bcl-2. The results of the cell cycle analysis suggested that Quina arrested HCE-4 cells in the G0/G1 cycle by downregulating cyclin-dependent (CDK) 2/4, cyclin D1/E and upregulating the levels of p21 and p27. We also found that Quina activated mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription-3 (STAT3) and nuclear factor kappa B (NF-κB) signaling pathways. Furthermore, Quina significantly increased intracellular reactive oxygen species (ROS) level. The pretreatment of N-acetyl-L-cysteine (NAC) blocked the apoptosis induced by Quina and inhibited the activities of MAPK, STAT3, and NF-κB signaling pathways. These results indicate that Quina induces the apoptosis in HCE-4 cells, which is via accumulating ROS generation and regulating MAPK, STAT3, and NF-κB. In conclusion, this study demonstrated that Quina have good therapeutic effects on human esophageal cancer cells.


Assuntos
Antraquinonas/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Esofágicas/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
19.
Neuroscience ; 455: 79-88, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33285236

RESUMO

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing among these areas. Three tonotopically organized core fields, namely, the primary (A1), anterior (AAF), and ventral (VAF) auditory fields, as well as one non-tonotopically organized belt field, the dorsal belt (DB), were identified based on their response properties. Compared to neurons in A1, AAF and VAF, units in the DB exhibited little or no response to pure tones but strong responses to white noise. The few DB neurons responded to pure tones with thresholds greater than 60 dB SPL, which was significantly higher than the thresholds of neurons in the core regions. In response to white noise, units in DB showed significantly longer latency and lower peak response, as well as longer response duration, than those in the core regions. Responses to repeated white noise were also examined. In contrast to neurons in A1, AAF and VAF, DB neurons could not follow repeated stimulation at a 300 ms inter-stimulus interval (ISI) and showed a significant steeper ISI tuning curve slope when the ISI was increased from 300 ms to 4.8 s. These results indicate that the DB processes auditory information on broader spectral and longer temporal scales than the core regions, reflecting a distinct role in the hierarchical cortical pathway.


Assuntos
Estimulação Acústica , Córtex Auditivo , Vias Auditivas , Mapeamento Encefálico , Animais , Neurônios , Ratos , Vigília
20.
Tohoku J Exp Med ; 252(4): 297-307, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33239483

RESUMO

Wnt1-inducible signaling pathway protein 1 (WISP1) regulates cell proliferation, differentiation, adhesion, migration and survival. Abnormal WISP1 expression is associated with the carcinogenesis of hepatocellular carcinoma (HCC). Aberrant DNA methylation is one of the major epigenetic alterations in HCC. However, the methylation status of the WISP1 promoter is still unclear. We therefore aimed to determine the methylation status of the WISP1 promoter and evaluate its clinical value in HCC. The study enrolled 251 participants, including 123 participants with HCC, 90 participants with chronic hepatitis B (CHB) and 38 healthy controls (HCs). WISP1 methylation status, mRNA levels and plasma soluble WISP1 were detected by methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. We found that the methylation frequency of WISP1 in patients with HCC was significantly lower than that in patients with CHB and HCs, while the relative expression levels of WISP1 mRNA were markedly higher in patients with HCC than in patients with CHB and HCs. Furthermore, the plasma soluble WISP1 in patients with HCC was obviously lower than in that in patients with CHB and HCs. Alpha-fetoprotein (AFP) is a widely recognized biomarker to diagnose HCC which lacks enough sensitivity and specificity. WISP1 promoter methylation status combined with AFP significantly improved the diagnostic ability in discriminating HCC from CHB compared with AFP or WISP1 methylation status alone. In conclusion, hypomethylation of the WISP1 gene promoter may serve as a noninvasive biomarker for detecting HBV-associated HCC.


Assuntos
Proteínas de Sinalização Intercelular CCN/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Metilação de DNA/genética , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Sequência de Bases , Proteínas de Sinalização Intercelular CCN/sangue , Proteínas de Sinalização Intercelular CCN/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC
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