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1.
Int J Ophthalmol ; 13(8): 1306-1311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821686

RESUMO

AIM: To identify mutations with whole exome sequencing (WES) in a Chinese X-linked retinitis pigmentosa (XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from peripheral blood and subjected to SureSelect Human All Exon 6+ UTR exon capture kit. The exons were sequenced as 100 base paired reads on Illumina HiSeq2500 system. Only mutations that resulted in a change in amino acid sequence were selected. A pattern of inheritance of the RP family was aligned to identified causal mutation. RESULTS: We analysed the data of WES information from XLRP family. The analysis revealed a hemizygous large genomic deletion of RPGR c.29_113del was responsible for this XLRP. The gross deletion lead to a frame-shift mutation and generate stop codon at 7 animo acid behind Asp (D10Afs*7), which would serious truncate RPGR protein. The novel frame-shift mutation was found to segregate with retinitis pigmentosa (RP) phenotype in this family. Bilateral myopia was present on the male patients, but carrier female showed unilateral myopia without RP. CONCLUSION: Our study identifies a novel frame-shift mutation of RPGR in a Chinese family, which would expand the spectrum of RPGR mutations. The geno-phenotypic analysis reveals a correlation between RP and myopia. Although exact mechanism of RP related myopia is still unknown, but the novel frame-shift mutation will give our hit on studying the molecular pathogenesis of RP and myopia.

2.
Gene ; 758: 144946, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32649978

RESUMO

Hepatic injury is one of the most challenging diseases in clinical medicine. Hepatic injury is accompanied by hepatocyte apoptosis and leads to hepatic fibrosis and cirrhosis, which may cause liver cancer and increased mortality. Therefore, it is essential to investigate the regulation mechanism and therapeutic strategies for hepatic injury. In the study, the effects of Thymosin ß4 (Tß4) on Long intergenic noncoding RNA-p21 (lincRNA-p21)-mediated liver injury were investigated. Results showed that lincRNA-p21 overexpression promoted hepatocytes apoptosis, which was blocked by Tß4. Besides, Tß4 reversed the levels of cleaved caspase-3 and caspase-9 induced by lincRNA-p21. LincRNA-p21 overexpression also caused the pathological injury and fibrosis in hepatic tissues and increased the levels of fibrosis-related proteins (Collagen I, α-SMA and TIMP-1), and induced hydroxyproline and ALT production. However, Tß4 reversed the effects of overexpression of lincRNA-p21 on hepatic injury and fibrosis. In vitro experiments, after lincRNA-p21 was overexpressed in hepatic stellate cells (HSCs), the proliferation ability and the levels of HSCs markers α-SMA and Desmin were increased. However, Tß4 reversed the effects of lincRNA-p21 on HSCs. Furthermore, the PI3K-AKT-NF-κB pathway was activated by lincRNA-p21, which was then reversed by the Tß4 administration. After the mice treated by insulin-like growth factor-1 (IGF-1) (the activator of PI3K-AKT), the inhibitory effect of Tß4 on activated the PI3K-AKT-NF-κB pathway was abrogated. Besides, IGF-1 abolished the protective effects of Tß4 on hepatic apoptosis and fibrosis induced by lincRNA-p21. Therefore, Tß4 reversed. lincRNA-p21-mediated liver injury through inhibiting PI3K-AKT-NF-κB pathway. Tß4 may be a promising drug for fibrosis therapy.


Assuntos
Apoptose/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Fígado/lesões , RNA Longo não Codificante/genética , Timosina/farmacologia , Actinas/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Hepatócitos/patologia , Proteínas I-kappa B/antagonistas & inibidores , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Inibidor Tecidual de Metaloproteinase-1/metabolismo
3.
Soft Matter ; 16(23): 5450-5457, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32483563

RESUMO

The adsorption and wetting on quartz surfaces by aqueous solutions of xylyl-substituted biquaternary ammonium salt gemini surfactants with different spacer groups (C3 and C6), have been investigated. The interfacial properties of surfactant solutions such as contact angle, adhesional tension (γLV cos θ), quartz-water interfacial tension (γSL) as well as adhesion work (WA) have been estimated. The obtained results show that C3 and C6 have similar adsorption behavior on quartz surfaces. Before critical micelle concentration (cmc) is reached, the contact angles of gemini surfactants slowly increase with the increasing concentration, and the adsorption amount at the water-air interface is almost the same as those at a quartz-water interface. After reaching cmc, the gemini surfactant Cn molecules form a more compact adsorption film through bending the flexible spacer chain, instead of forming a bi-layer. As a result, a further increase in quartz-liquid interfacial tension (γSL) and a consequent increase in contact angle have been observed after cmc. Gemini C6 shows a stronger ability towards hydrophobic modification at a quartz surface than C3, demonstrating the contribution of the longer methylene spacer to the hydrophobic modification of the quartz surface.

4.
Neurosci Bull ; 36(2): 153-164, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31444653

RESUMO

Fear memories are critical for survival. Nevertheless, over-generalization of these memories, depicted by a failure to distinguish threats from safe stimuli, is typical in stress-related disorders. Previous studies have supported a protective role of ketamine against stress-induced depressive behavior. However, the effect of ketamine on fear generalization remains unclear. In this study, we investigated the effects of ketamine on fear generalization in a fear-generalized mouse model. The mice were given a single sub-anesthetic dose of ketamine (30 mg/kg, i.p.) 1 h before, 1 week before, immediately after, or 22 h after fear conditioning. The behavioral measure of fear (indicated by freezing level) and synaptic protein expression in the basolateral amygdala (BLA) and inferior-limbic pre-frontal cortex (IL-PFC) of mice were examined. We found that only ketamine administered 22 h after fear conditioning significantly decreased the fear generalization, and the effect was dose-dependent and lasted for at least 2 weeks. The fear-generalized mice showed a lower level of brain-derived neurotrophic factor (BDNF) and a higher level of GluN2B protein in the BLA and IL-PFC, and this was reversed by a single administration of ketamine. Moreover, the GluN2B antagonist ifenprodil decreased the fear generalization when infused into the IL-PFC, but had no effect when infused into the BLA. Infusion of ANA-12 (an antagonist of the BDNF receptor TrkB) into the BLA or IL-PFC blocked the effect of ketamine on fear generalization. These findings support the conclusion that a single dose of ketamine administered 22 h after fear conditioning alleviates the fear memory generalization in mice and the GluN2B-related BDNF signaling pathway plays an important role in the alleviation of fear generalization.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Condicionamento Clássico/efeitos dos fármacos , Medo/efeitos dos fármacos , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Ying Yong Sheng Tai Xue Bao ; 30(9): 2992-2998, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31529874

RESUMO

Long-term overuse of grasslands results in quantitative and qualitative decline of forage yield. Nutrient supplementation is a key strategy to improve forage yield. While mounting evidence showed that nitrogen (N) supplementation can increase forage yield, little is known about its impacts on forage quality. To understand the effects of N supplementation on forage quality at the community level, we carried out a field experiment in the meadow steppe of Hulunbuir. Our results showed that N supplementation significantly increased forage yield by 23%, which was mainly due to positive responses of perennial rhizomatous grass. The yield of other plant functional groups showed neutral response to N supplementation. The concentrations of crude protein, crude fat, and crude fiber varied significantly among different plant functional groups. Nitrogen supplementation significantly enhanced the concentration of crude protein in rhizomatous grass, bunchgrass, legume, and sedge. It enhanced the content of crude fat in rhizomatous grass but with no effect on other functional groups. Nitrogen supplementation had no effect on the concentration of crude fibre in all functional groups. At the community level, N supplementation significantly increased the concentrations of crude protein and crude fat. Our results are important for understanding the responses of forage production in meadow steppe under the scenarios of N enrichment.


Assuntos
Pradaria , Nitrogênio , Poaceae , China , Fertilizantes
6.
Brain Behav ; 9(8): e01280, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31313894

RESUMO

BACKGROUND: Fear renewal, the context-specific relapse of a conditioned fear after extinction, is a widely pursued model of post-traumatic stress disorder and phobias. However, its cellular and molecular mechanisms remain poorly understood. The dentate gyrus (DG) has emerged as a critical locus of plasticity with relevance to memory, anxiety disorders, and depression, and it contributes to fear memory retrieval. Here, we have identified the role of the DG in fear renewal and its molecular mechanism. MATERIALS AND METHODS: Muscimol (MUS), activator of cyclic adenosine monophosphate (cAMP) forskolin (FSK), inhibitor of protein kinase A (PKA), Rip-cAMP, and a phosphodiesterase inhibitor rolipram were infused into DG of standard deviation rats before renewal testing. cAMP levels after fear renewal was measured by enzyme-linked immunosorbent assay. The protein levels of phosphodiesterase 4 (PDE4) isoforms were tested by western blot. At last, the roles of cAMP signaling were also tested in the acquisition of fear conditioning, fear retrieval, and extinction. RESULTS: Intra-DG treatment of MUS and Rp-cAMP impaired fear renewal. FSK and rolipram exhibited the opposite effect, which also occurred in the retrieval of original fear memory. This change in fear renewal was regulated by PDE4 isoforms PDE4A, PDE4A5, and PDE4D. In addition, FSK and rolipram facilitated the acquisition of fear conditioning in long-term memory, but not short-term memory, while Rp-cAMP impaired long-term memory. For extinction, FSK and rolipram inhibited extinction process, while Rp-cAMP facilitated fear extinction. CONCLUSION: These findings demonstrated that fear renewal activated cAMP signaling in the DG through decreased PDE4 activity. Because of the role of cAMP signaling in the acquisition or retrieval of fear conditioning and encoding of extinction, it is speculated that initial learning and extinction may have similarities in molecular mechanism, especially fear retrieval and fear renewal may share cAMP signaling pathway in the DG.


Assuntos
AMP Cíclico/metabolismo , Giro Denteado/metabolismo , Medo/fisiologia , Memória/fisiologia , Transdução de Sinais/fisiologia , Animais , Colforsina/farmacologia , Giro Denteado/efeitos dos fármacos , Medo/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/farmacologia , Ratos , Ratos Sprague-Dawley , Rolipram/farmacologia , Transdução de Sinais/efeitos dos fármacos
8.
J Craniofac Surg ; 30(5): 1601-1604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31299778

RESUMO

Facial anthropometric measurements play an important part not only in forensic cases but also in clinical treatments. The utilization of 2D photograph methods in facial anthropometric studies to found database with age, gender, ethnicity, and region was expanded by other races but little for Han nationality. This study was undertaken to describe reference ranges of facial anthropometric proportions of Han nationality and compare the anthropometric characteristics with other ethnicities. Our subjects focused on full-face photos of Han nationality in South China which consisted of 1176 healthy person (425 adult males, 421 adult females and 157 underage boys and 173 underage girls). Eight anthropometric landmarks on photos were examined by ImageJ software, and 7 anthropometric ratios were analyzed. The results indicated sex- and age- and ethnics-related anthropometric variations in Chinese Han nationality in South China. For adults, females have larger ratios in intercanthal-nasal width and lip height index and smaller nose width index; for impubes, boys were larger in lip height index and smaller in lip width ratios than girls, but as age achieved, the underage boys and girls exhibited a significantly larger nose width index and lip width index, smaller canthal index, intercanthal-nasal width and lip height index. Comparing with Japanese, India, North American and Persian, Chinese Han showed great difference in facial anthropometric proportions.


Assuntos
Antropometria , Antropometria/métodos , China/etnologia , Pálpebras/anatomia & histologia , Face/anatomia & histologia , Feminino , Humanos , Índia , Masculino , Valores de Referência
9.
Rev Sci Instrum ; 90(4): 045114, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31043014

RESUMO

Cam mechanism is widely applied in industry because it can help achieve various complex motions of the follower via the cam contour design. However, its performance is significantly affected by the wear condition. This study proposes a load distribution measurement instrument to assist the study on friction and wear regularities of oscillating follower cam mechanisms through obtaining the normal pressure (F) and friction force (Ff) distributions along the cam profile. In the instrument, F and Ff are automatically calculated via a MATLAB program based on the geometry and the measured rotary resistance torque and rotary angle of the cam. The latter two parameters are obtained through a static torque sensor and a rotary encoder built in servo motor in real time, respectively. An experimental test was conducted and the cam morphology after service was observed using scanning electron microscopy. Results show that the wear condition of the cam is significantly related to the corresponding F and Ff. Complex load parameters of oscillating follower cam mechanisms can be provided by this instrument, which is crucial in understanding the friction and wear behaviors of cams and finding the vulnerable position.

10.
Front Behav Neurosci ; 13: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894805

RESUMO

Glucocorticoids (GCs) can modulate the memory enhancement process during stressful events, and this modulation requires arousal-induced norepinephrine (NE) activation in the basolateral amygdale (BLA). Our previous study found that an intrahippocampal infusion of propranolol dose-dependently induced post-traumatic stress disorder (PTSD)-like memory impairments. To explore the role of the noradrenergic system of the BLA in PTSD-like memory impairment, we injected various doses of NE into the BLA. We found that only a specific quantity of NE (0.3 µg) could induce PTSD-like memory impairments, accompanied by a reduction in phosphorylation of GluR1 at Ser845 and Ser831. Moreover, this phenomenon could be blocked by a protein kinase A (PKA) inhibitor or calcium/calmodulin-dependent protein kinase II (CaMK II) inhibitor. These findings demonstrate that NE could induce PTSD-like memory impairments via regulation of the ß-adrenoceptor receptor (ß-AR)-3',5'-cyclic monophosphate (cAMP)/PKA and CaMK II/PKC signaling pathways.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30025794

RESUMO

Previous studies support a critical role of hippocampus in contextual fear memory. Structural and functional alterations of hippocampus occur frequently in posttraumatic stress disorders (PTSD). Recent reports reveal that knockout of CLC-3, a member of the CLC family of anion channels and transporters, leads to neuronal degeneration and loss of hippocampus. However, the role of CLC-3 in contextual fear memory remains unknown. Using adenovirus and adeno-associated virus gene transfer to knockdown CLC-3 in hippocampal CA1, we investigate the role of CLC-3 in contextual fear memory. CLC-3 expression is increased in hippocampal CA1 after formation of long-term contextual fear memory. Knockdown of CLC-3 by adenovirus infusion in hippocampal CA1 significantly attenuates the contextual fear memory, reduces spine density, induces defects of excitatory synaptic ultrastructure showed by the decreased PSD length, PSD thickness and active zone length, and impairs L-LTP induction and maintenance. Knockdown of CLC-3 also induces the synaptic NMDAR subunit composition to an increased GluN2A/GluN2B ratio pattern and reduces the activity of CaMKII-α. Furthermore, selectively knockdown of CLC-3 in excitatory neurons by adeno-associated virus driven from CaMKII-α promoter is sufficient to impair long-term contextual fear memory. These findings highlight that CLC-3 in hippocampal CA1 is necessary for contextual fear memory.


Assuntos
Região CA1 Hipocampal/metabolismo , Canais de Cloreto/deficiência , Medo/fisiologia , Memória/fisiologia , Animais , Região CA1 Hipocampal/patologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Canais de Cloreto/genética , Condicionamento Psicológico/fisiologia , Dependovirus/genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Vetores Genéticos , Potenciação de Longa Duração/fisiologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , RNA Interferente Pequeno , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , Sinapses/patologia , Técnicas de Cultura de Tecidos
12.
Sci Total Environ ; 654: 960-968, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30453265

RESUMO

There is considerable debate regarding how the taxonomic diversity of microbial communities relates to the functional diversity across space while similar questions have been explored in macro-organism communities. Here, we investigated the taxonomic and functional diversity patterns of soil microbial communities by coupling the data obtained from marker genes sequencing and functional gene surveys. Meanwhile, we evaluated the relative effects of environment and geographic distance on shaping these patterns in alpine grasslands of northern China. Although the taxonomic diversity and composition of microbial communities varied across sites, we found no consistent changes in the functional structure. Both the environmental factors and geographic distance concurrently affected the taxonomic diversity patterns but they had no effects on the spatial variations in functional genes. The functional alpha diversity was weakly correlated to the taxonomic alpha diversity across sites. Moreover, we found no significant relationship between the taxonomic and functional composition similarity among microbial communities. Together, our results provide evidence that spatial variation in microbial functions could be independent of their variations in taxonomic diversity. Even the drivers of spatial variations in the functional structure could be totally different from those of taxonomic variations such as environmental differences and dispersal limitation. Our findings suggest that spatial variations of microbial function structure within a community would not follow the variations of taxonomic structures due to different drivers between both of them over space.


Assuntos
Pradaria , Microbiota , Microbiologia do Solo , Bactérias/genética , China , DNA Espaçador Ribossômico/análise , Genes Bacterianos , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Análise de Sequência de RNA
13.
Int J Neuropsychopharmacol ; 21(11): 1037-1048, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169690

RESUMO

Background: Early-life stress increases the risk for posttraumatic stress disorder. However, the epigenetic mechanism of early-life stress-induced susceptibility to posttraumatic stress disorder in adulthood remains unclear. Methods: Rat pups were exposed to maternal deprivation during postnatal days 1 to 14 for 3 hours daily and treated with the DNA methyltransferase inhibitor zebularine, L-methionine, or vehicle 7 days before contextual fear conditioning, which was used as a second stress and to mimic the reexperiencing symptom of posttraumatic stress disorder in adulthood. Long-term potentiation, dendritic spine density, DNA methyltransferase mRNA, Reelin gene methylation, and Reelin protein expression in the hippocampal CA1 were measured. Results: Maternal deprivation enhanced contextual fear memory in adulthood. Meanwhile, maternal deprivation decreased DNA methyltransferase mRNA and Reelin gene methylation in the hippocampal CA1 on postnatal days 22 and 90. Reelin protein expression was increased in the hippocampal CA1 following contextual fear conditioning in adulthood. Furthermore, compared with rats that experienced maternal deprivation alone, rats also exposed to contextual fear conditioning showed an enhanced induction of hippocampal long-term potentiation and increased dendritic spine density in the hippocampal CA1 following contextual fear conditioning in adulthood. Zebularine pretreatment led to an enhancement of contextual fear memory, hypomethylation of the Reelin gene, and increased Reelin protein expression in adult rats, while L-methionine had the opposite effects. Conclusions: Maternal deprivation can epigenetically program second-hit stress-induced Reelin expression and enhance the susceptibility to contextual fear memory in adulthood. These findings provide a new framework for understanding the cumulative stress hypothesis.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Medo/fisiologia , Privação Materna , Memória/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Serina Endopeptidases/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Estresse Psicológico/metabolismo , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/crescimento & desenvolvimento , Região CA1 Hipocampal/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Modelos Animais de Doenças , Epigênese Genética/efeitos dos fármacos , Medo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Memória/efeitos dos fármacos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Técnicas de Cultura de Tecidos
14.
Brain Behav ; 8(2): e00905, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29484264

RESUMO

Introduction: One hallmark symptom of post-traumatic stress disorder (PTSD) is an inability to restrict fear responses to the appropriate predictor. An infusion of glucocorticoids (GCs) after a high-intensity shock has been shown to induce PTSD-like memory impairments. In addition to GCs, noradrenergic signalling is also recognized as a key biomarker underlying PTSD symptomatology. Methods: To explore the role of the noradrenergic system in PTSD-like memory impairments, in this study, various doses of the ß-adrenoceptor antagonist propranolol were systemically or bilaterally injected into the dorsal hippocampus immediately after unpaired cue-shock contextual fear conditioning, and then the rats were tested 24 h later. Results: Interestingly, we found that only low-dose propranolol could induce PTSD-like memory impairments, as rats showed reduced freezing to the correct predictor and generalized fear responses to the safe cues, accompanied by increased NE levels in the hippocampus and altered neural activity within the frontal-subcortical circuit. Conclusion: These findings demonstrate that the noradrenergic system is involved in regulating the consolidation of contextual fear memory and that propranolol can dose-dependently induce PTSD-like memory impairments.


Assuntos
Hipocampo , Transtornos da Memória , Propranolol/farmacologia , Transtornos de Estresse Pós-Traumáticos , Antagonistas Adrenérgicos beta/farmacologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medo/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Memória/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Ratos , Ratos Sprague-Dawley , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/psicologia
15.
Oncol Lett ; 11(4): 2353-2358, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27073479

RESUMO

Previous in vivo and in vitro studies have shown that human mesenchymal stem cells (MSCs) exhibit tropism for gliomas. However, the mechanism underlying this directed migration remains unclear. The aim of the present study was to investigate the possible mechanism underlying platelet-derived growth factor-BB (PDGF-BB)-induced chemotactic migration of bone marrow-derived MSCs (BMSCs) toward glioma. Rat glioma C6 cell-conditioned medium was utilized to evaluate the chemotactic response of BMSCs toward glioma using an in vitro migration assay. Recombinant rat PDGF-BB was added to C6 cell-conditioned medium to assess its effect on the tropism of BMSCs. The effect of PDGF-BB on the expression levels of cluster of differentiation (CD)44 in BMSCs was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence assays. The results revealed that chemotactic migration was induced in BMSCs by rat glioma C6 cell-conditioned medium, which was enhanced by PDGF-BB treatment in a dose-dependent manner. Furthermore, RT-PCR and immunofluorescence assays showed that CD44 expression was upregulated in BMSCs following treatment with 40 ng/ml PDGF-BB for 12 h. Additionally, 3-h pretreatment with the anti-CD44 neutralizing antibody OX-50 was observed to attenuate the tropism of BMSCs toward glioma in the presence or absence of PDGF-BB. The results of the present study indicate that CD44 mediates the tropism of BMSCs toward glioma, and PDGF-BB promotes the migration of BMSCs toward glioma via the upregulation of CD44 expression in BMSCs. These findings suggest CD44 inhibition may be a potential therapeutic target for the treatment of glioma.

16.
Biochem Biophys Res Commun ; 472(4): 656-61, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26969275

RESUMO

Exposure to a novel environment enhances the extinction of contextual fear through the "tagging-and-capture" process. However, the underlying molecular mechanisms of novelty-induced enhancement of fear extinction are still unclear. NMDA receptor activity was recently revealed to be required for the enhancement of fear extinction caused by exposure to novelty. Src family kinases (SFKs) act as a molecular hub for regulation of NMDA receptors. We hypothesized that SFKs might be involved in novelty-induced enhancement of fear extinction. We found that the enhancement of fear extinction induced by novelty exposure is accompanied by Src kinase phosphorylation and activation in a restricted time window. Furthermore, intrahippocampal infusion of SFKs inhibitor PP2 inhibits Src kinase phosphorylation and activation, attenuates the activation of NR2B-containing NMDA receptors, and thereby reverses the enhancement of fear extinction induced by novelty exposure. These results suggested that Src kinase may serve as a behavioral tag in the procedural enhancement of fear extinction by novelty exposure.


Assuntos
Ativação Enzimática , Comportamento Exploratório , Medo/fisiologia , Hipocampo/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Quinases da Família src/metabolismo , Animais , Masculino , Fosforilação , Ratos Sprague-Dawley
17.
Chin Med J (Engl) ; 129(4): 448-55, 2016 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-26879019

RESUMO

OBJECTIVE: This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (ß2M), a conservative immune molecule in vertebrate. DATA SOURCES: The data used in this review were obtained from PubMed up to October 2015. Terms of ß2M, immune response, and infection were used in the search. STUDY SELECTIONS: Articles related to ß2M were retrieved and reviewed. Articles focusing on the characteristic and function of ß2M were selected. The exclusion criteria of articles were that the studies on ß2M-related molecules. RESULTS: ß2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of ß2M is associated with multiple diseases, including endogenous and infectious diseases. ß2M could directly participate in the development of cancer cells, and the level of ß2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis. CONCLUSIONS: Based on the characteristic of ß2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, ß2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of ß2M on applications.


Assuntos
Microglobulina beta-2/fisiologia , Antígenos CD1/fisiologia , Proteína da Hemocromatose/análise , Antígenos de Histocompatibilidade Classe I/fisiologia , Humanos , Receptores Fc/fisiologia , Microglobulina beta-2/sangue , Microglobulina beta-2/química , Microglobulina beta-2/deficiência
18.
Artigo em Inglês | MEDLINE | ID: mdl-26186395

RESUMO

Many macrofungus sclerotia are well-known medicinal herbs, health food and nutritional supplements. However, the prevalent adulterant commercial products are major hindrances to their incorporation into mainstream medical use in many countries. The mushroom sclerotia of Lignosus rhinocerotis, Poria cocos, Polyporus umbellatus, Pleurotus tuber-regium and Omphalia lapidescens are commonly used in traditional Chinese medicine. In this study, IR macro-fingerprint method was used in the identification of these sclerotia. The results showed that the spectrum of L. rhinocerotis (LR) was comparable with P. cocos with 94.4% correlation, except that the peak at 1543cm(-1) of LR appeared in lower intensity. The spectrum of P. umbellatus and P. tuber-regium was also correlated (91.5%), as both spectra could be clearly discriminated in that P. umbellatus spectrum has small base peaks located at the range of 1680-1500cm(-1). O. lapidescens was not comparable with all the other sclerotia as its spectrum was totally different. Its base peak was broad and derivated equally along the range. The first IR has revealed the dissimilarity among five mushrooms sclerotia. The second derivative and 2DIR further enhanced the identification in detail.


Assuntos
Agaricales/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Medicina Tradicional Chinesa , Pleurotus/química , Polyporus/química , Poria/química
19.
World J Gastroenterol ; 21(17): 5295-302, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25954103

RESUMO

AIM: To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype 6 (GII.6) strain norovirus in Shanghai, China. METHODS: Noroviruses are responsible for approximately half of all reported gastroenteritis outbreaks in many countries. Genogroup 2 genotype 4 strains are the most prevalent. Rare outbreaks caused by GII.6 strains have been reported. An acute gastroenteritis outbreak occurred in an elementary school in Shanghai in December of 2013. Field and molecular epidemiologic investigations were conducted. RESULTS: The outbreak was limited to one class in an elementary school located in southwest Shanghai. The age of the students ranged from 9 to 10 years. The first case emerged on December 10, 2013, and the last case emerged on December 14, 2013. The cases peaked on December 11, 2013, with 21 new cases. Of 45 students in the class, 32 were affected. The main symptom was gastroenteritis, and 15.6% (5/32) of the cases exhibited a fever. A field epidemiologic investigation showed the pathogen may have been transmitted to the elementary school from employees in a delicatessen via the first case student, who had eaten food from the delicatessen one day before the gastroenteritis episodes began. A molecular epidemiologic investigation identified the cause of the gastroenteritis as norovirus strain GII.6; the viral sequence of the student cases showed 100% homology with that of the shop employees. Genetic relatedness analyses showed that the new viral strain is closely related to previously reported GII.6 sequences, especially to a strain reported in Japan. CONCLUSION: This is the first report to show that norovirus strain GII.6 can cause a gastroenteritis outbreak. Thus, the prevalence of GII.6 noroviruses requires attention.


Assuntos
Infecções por Caliciviridae/virologia , Surtos de Doenças , Gastroenterite/virologia , Norovirus/patogenicidade , Doença Aguda , Infecções por Caliciviridae/diagnóstico , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/transmissão , Criança , China/epidemiologia , Busca de Comunicante , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Genótipo , Humanos , Epidemiologia Molecular , Norovirus/classificação , Norovirus/genética , Filogenia , RNA Viral/genética , Estudos Retrospectivos , Instituições Acadêmicas
20.
Oncotarget ; 6(13): 11585-99, 2015 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-25839162

RESUMO

TMEM16A is a newly identified calcium activated chloride channel, and has been reported to be overexpressed by various solid malignant cancers to promote proliferation and invasion, yet little is known about its role in gastric cancer(GC). Therefore, we investigated the role of TMEM16A in GC and its clinical significance by a retrospective analysis of 367 GC patients, and in vitro study was performed for validation and underlying molecular mechanism.TMEM16A was significantly upregulated and amplified in GC tissues, and its overexpression was positively correlated with disease stage, negatively with patient survival and identified as an independent prognostic factor for patient outcome. A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens. TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-ß secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823). Supplement of TGF-ß reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Movimento Celular , Canais de Cloreto/metabolismo , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anoctamina-1 , Antígenos CD , Biomarcadores Tumorais/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Canais de Cloreto/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Interferência de RNA , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Transfecção , Regulação para Cima
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