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2.
Genes (Basel) ; 10(7)2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319533

RESUMO

The growth traits are important traits in chickens. Compared to white feather broiler breeds, Chinese local broiler breeds have a slow growth rate. The main genes affecting the growth traits of local chickens in China are still unclear and need to be further explored. This experiment used fast-growth and slow-growth groups of the Jinghai Yellow chicken as the research objects. Three males and three females with similar body weights were selected from the two groups at four weeks old and eight weeks old, respectively, with a total of 24 individuals selected. After slaughter, their chest muscles were taken for transcriptome sequencing. In the differentially expressed genes screening, all of the genes obtained were screened by fold change ≥ 2 and false discovery rate (FDR) < 0.05. For four-week-old chickens, a total of 172 differentially expressed genes were screened in males, where there were 68 upregulated genes and 104 downregulated genes in the fast-growth group when compared with the slow-growth group. A total of 31 differentially expressed genes were screened in females, where there were 11 upregulated genes and 20 downregulated genes in the fast-growth group when compared with the slow-growth group. For eight-week-old chickens, a total of 37 differentially expressed genes were screened in males. The fast-growth group had 28 upregulated genes and 9 downregulated genes when compared with the slow-growth group. A total of 44 differentially expressed genes were screened in females. The fast-growth group had 13 upregulated genes and 31 downregulated genes when compared with the slow-growth group. Through gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, many genes were found to be related to cell proliferation and differentiation, muscle growth, and cell division such as SNCG, MCL1, ARNTL, PLPPR4, VAMP1, etc. Real-time PCR results were consistent with the RNA-Seq data and validated the findings. The results of this study will help to understand the regulation mechanism of the growth and development of Jinghai Yellow chicken and provide a theoretical basis for improving the growth rate of Chinese local chicken breeds.

3.
J Hematol Oncol ; 12(1): 59, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186046

RESUMO

Harnessing the power of the immune system to recognize and eliminate cancer cells is a longtime exploration. In the past decade, monoclonal antibody (mAb)-based immune checkpoint blockade (ICB) and chimeric antigen receptor T (CAR-T) cell therapy have proven to be safe and effective in hematologic malignancies. Despite the unprecedented success of ICB and CAR-T therapy, only a subset of patients can benefit partially due to immune dysfunction and lack of appropriate targets. Here, we review the preclinical and clinical advances of CTLA-4 and PD-L1/PD-1-based ICB and CD19-specific CAR-T cell therapy in hematologic malignancies. We also discuss the basic research and ongoing clinical trials on emerging immune checkpoints (Galectin-9/Tim-3, CD70/CD27, LAG-3, and LILRBs) and on new targets for CAR-T cell therapy (CD22, CD33, CD123, BCMA, CD38, and CD138) for the treatment of hematologic malignancies.

4.
Cell Rep ; 27(10): 3034-3048.e5, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167146

RESUMO

Dermal γδT cells play critical roles in skin homeostasis and inflammation. However, the underlying molecular mechanisms by which these cells are activated have not been fully understood. Here, we show that the mechanistic or mammalian target of rapamycin (mTOR) and STAT3 pathways are activated in dermal γδT cells in response to innate stimuli such as interleukin-1ß (IL-1ß) and IL-23. Although both mTOR complex 1 (mTORC1) and mTORC2 are essential for dermal γδT cell proliferation, mTORC2 deficiency leads to decreased dermal γδT17 cells. It appears that mitochondria-mediated oxidative phosphorylation is critical in this process. Notably, although the STAT3 pathway is critical for dermal Vγ4T17 effector function, it is not required for Vγ6T17 cells. Transcription factor IRF-4 activation promotes dermal γδT cell IL-17 production by linking IL-1ß and IL-23 signaling. The absence of mTORC2 in dermal γδT cells, but not STAT3, ameliorates skin inflammation. Taken together, our results demonstrate that the mTOR-STAT3 signaling differentially regulates dermal γδT cell effector function in skin inflammation.

5.
BMJ Open ; 9(5): e024764, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31061023

RESUMO

OBJECTIVE: Animal injury is a significant cause of morbidity and mortality worldwide. Dog bites account for tens of millions of injuries annually and the highest risk is among children. However, children may not receive postexposure prophylaxis (PEP) treatment timely and appropriately after rabies exposure. This study aimed to investigate the characteristics and factors associated with PEP treatment of dog and cat bites among left-behind children. DESIGN: A cross-sectional study using questionnaire was conducted in primary and high schools. SETTING: Shenzhen and Shantou cities, Guangdong Province, China. PARTICIPANTS: A total of 9380 participants were included and 2236 of them were with a history of dog and cat bites. RESULTS: 1188 (53.1%) boys and 1048 (46.9%) girls suffered from animal bites. Bitten in holidays was less likely to receive PEP treatment (OR 0.512, 95% CI 0.377 to 0.695) than those bitten in school days. Bitten while being with family (OR 1.418, 95% CI 1.040 to 1.934) and bitten at roadside (OR 1.842, 95% CI 1.297 to 2.171), bitten by unvaccinated animals (OR 1.745, 95% CI 1.246 to 2.443) tended to receive PEP treatment. Compared with unbroken skin, bleeding (OR 1.789, 95% CI 1.165 to 2.745) and laceration (OR 3.834, 95% CI 2.310 to 6.366) were showed as treatment prompting factors. CONCLUSIONS: Bitten in holidays was found as a risk factor of receiving PEP treatment of animal bites. Certain measures should be taken to raise left-behind children's awareness of receiving PEP treatment timely and appropriately after dog and cat bites.

6.
Anim Biotechnol ; : 1-11, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961447

RESUMO

Chicken is popular among consumers in the market, but the mechanism for regulating its growth is still unclear. In this experiment, two groups of Bian chickens of different body weights at 16 weeks of age were studied. The leg muscles were taken for transcriptome sequencing after slaughter. In the differential gene screening, all the genes obtained by sequencing the fast and slow growth groups were screened by Fold Change ≥2 and False Discovery Rate (FDR) <0.05, and 108 differentially expressed genes were obtained. The slow growth group has 17 up-regulated genes and 91 down-regulated genes compared with the fast growing group. Significance analysis of differentially expressed genes in gene ontology (GO) enrichment indicates that there are 65, 16 and 6 significantly enriched entries in the three main categories of biological processes, cellular components and molecular functions (P-value <0.05), respectively. Pathway enrichment analysis yielded three significantly enriched signal pathways: Adrenergic signaling in cardiomyocytes, Cardiac muscle contraction and Tight junction. The experiment would contribute to reveal the molecular mechanism of chicken growth and provide a theoretical basis for improving the performance of Bian chicken.

7.
BMC Genomics ; 20(1): 96, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700247

RESUMO

BACKGROUND: Circular RNA (circRNA) is a type of noncoding RNA involved in a variety of biological processes, especially in post-transcriptional regulation. The granulosa cells of follicles play a determining role in ovarian development. However, the function of circRNA in chicken follicles is unclear. To better understand the molecular mechanism underlying follicular development and granulosa cell function, we performed a strategy of second-generation sequencing and linear RNA depletion for granulosa cells from small yellow follicles (SYF, 5-8 mm), the smallest hierarchal follicles (F6, 9-12 mm), and the largest hierarchal follicles (F1, ~ 40 mm). RESULTS: We predicted a total of 11,642 circRNAs that distributed on almost all chromosomes. The majority of the splice lengths of circRNAs were 200-500 nt and mainly produced from intron and CDS regions. During follicle growth, differentially expressed (DE) circRNAs showed dynamic changes which were tissue- and stage-specific. The host genes of DE circRNAs were functionally enriched in GTPase activity and several pathways involved in reproduction. Moreover, bioinformatic prediction analysis for circRalGPS2 demonstrated that circRNAs from the same genes may share common miRNA to act as a sponge. The predicted target genes were enriched in various biological processes including cognition, cell communication, and regulation of signaling, and several pathways related to reproduction such as tight junction, oocyte meiosis, progesterone-mediated oocyte maturation, and GnRH signaling. CONCLUSIONS: This study provides a starting point for further experimental investigations into chicken circRNAs and casts a light on the understanding of follicle development.


Assuntos
Galinhas/genética , Regulação da Expressão Gênica , Células da Granulosa/metabolismo , Folículo Ovariano/metabolismo , RNA/genética , Animais , Galinhas/crescimento & desenvolvimento , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Células da Granulosa/citologia , MicroRNAs/genética , Folículo Ovariano/citologia , Transdução de Sinais
8.
PLoS One ; 13(11): e0206131, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30403718

RESUMO

Chicken is widely favored by consumers because of some unique features. The leg muscles occupy an important position in the market. However, the specific mechanism for regulating muscle growth speed is not clear. In this experiment, we used Jinghai yellow chickens with different body weights at 300 days as research subjects. The chickens were divided into fast- and slow-growing groups, and we collected leg muscles after slaughtering for use in RNA-seq. After comparing the two groups, 87 differentially expressed genes (DEGs) were identified (fold change ≥ 2 and FDR < 0.05). The fast-growing group had 42 up-regulated genes and 45 down-regulated genes among these DEGs compared to the slow-growing group. Six items were significantly enriched in the biological process: embryo development ending in birth or egg hatching, chordate embryonic development, embryonic skeletal system development, and embryo development as well as responses to ketones and the sulfur compound biosynthetic process. Two significantly enriched pathways were found in the KEGG pathway analysis (P-value < 0.05): the insulin signaling pathway and the adipocytokine signaling pathway. This study provides a theoretical basis for the molecular mechanism of chicken growth and for improving the production of Jinghai yellow chicken.

9.
Exp Ther Med ; 15(6): 4763-4770, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29904395

RESUMO

The mammalian target of rapamycin (mTOR) signaling pathway has attracted much attention in recent years. However, the contribution of mTOR activation to the development of post-traumatic epilepsy (PTE) remains largely unknown. The purpose of the present study was to investigate the activation of mTOR signaling in a rat model of FeCl2-induced PTE, and to explore the potential effect of its specific inhibitor rapamycin. The results indicated that the expression levels of p-mTOR and p-P70S6K, the overactivation biomarkers of mTOR signaling, increased significantly in hippocampal and perilesional cortex following PTE induction. Notably, they were significantly decreased in the aformementioned brain regions following rapamycin treatment. Furthermore, the frequency and number of behavioral seizures and epileptic brain injury were also greatly reduced. These results suggest that hyperactivation of the mTOR signaling pathway is a crucial mechanism of PTE development, and it may be considered a novel therapeutic target for PTE treatment.

10.
J Clin Neurosci ; 54: 29-32, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29778299

RESUMO

OBJECTIVE: To seek a cerebral perfusion pressure (CPP) threshold that can reduce the occurrence of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We analyzed the clinical data of patients with the diagnosis of aSAH and underwent CPP monitoring in our department from February 2014 to December 2015. CPP was divided into four specified thresholds by every 10 mmHg increments, which were from 50 mmHg to 80 mmHg. The totally time ratio of CPP below each threshold was calculated. The correlation between the time ratio and DCI were analyzed using binary logistic regression. And receiver operating characteristic curve was performed to identify the cutoff time ratios at higher risk of DCI. RESULTS: Finally, 17 patients developed DCI from 60 patients who were recruited. The time ratios of CPP which was below 50 mmHg, 60 mmHg and 70 mmHg were found predictors of DCI by the binary logistic regression. The cutoff time ratios were 0.4% (AUC = 0.777), 7.0% (AUC = 0.702), 28.7% (AUC = 0.696) respectively. While at the level of 80 mmHg, the cutoff time ratio was 65% (AUC = 0.595). It was not related to DCI (P = 0.167). Patients suffered from DCI had a worse outcome than who did not at 3 month after aSAH (P = 0.018). CONCLUSION: Time ratios at higher risk of DCI had a positive relationship with the CPP thresholds. Keeping CPP above 70 mmHg may be helpful to prevent DCI after aSAH, but it still needs further investigation.


Assuntos
Isquemia Encefálica/prevenção & controle , Circulação Cerebrovascular/fisiologia , Hemorragia Subaracnóidea/fisiopatologia , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Hemorragia Subaracnóidea/complicações
11.
BMC Cancer ; 18(1): 500, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29716544

RESUMO

BACKGROUND: Inflammasomes are reported to be abnormally expressed and activated in several malignancies and play important roles in tumor development. The present study was designed to investigate the expression and function of the NLR family pyrin domain containing protein 3 (NLRP3) inflammasome in oral squamous cell carcinoma (OSCC). METHODS: NLRP3 expression in OSCC cell lines and the normal human immortalized oral epithelial cells (HIOEC) was determined by real-time PCR and western blot. Immunohistochemistry was used to examine the expression of NLRP3 and IL-1ß in the paraffin-embedded OSCC tissues. The proliferation of OSCC cells was detected by the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell colony formation ability of the OSCC cells was also evaluated. Tumor cell migration or invasion was measured by the transwell assay and related protein markers were determined by western blot. A mouse xenograft model was established to investigate the OSCC tumor growth in vivo. RESULTS: Significant higher expression of NLRP3 was observed in the OSCC cells. Obvious expression of NLRP3 and IL-1ß was found in the paraffin-embedded OSCC tissues, and the NLRP3 expression levels were correlated with the tumor size, lymphonode metastatic status and IL-1ß expression. Downregulating NLRP3 expression markedly reduced the cleavage of caspase-1 and production of IL-1ß in OSCC cells. NLRP3 knockdown also inhibited the proliferation, migration and invasion of OSCC cells. Further investigation indicated that expressions of E-cadherin and vimentin in OSCC cells were increased, while N-cadherin expression was decreased after NLRP3 knockdown. Downregulating NLRP3 expression in OSCC cells significantly reduced the tumor growth in vivo. CONCLUSIONS: Our data suggested that the increased expression of NLRP3 in OSCC was associated with tumor growth and metastasis. NLRP3 may be considered as a potential target for OSCC therapy.

12.
Am J Chin Med ; 46(4): 819-833, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29737211

RESUMO

Eclipta prostrata L. is a traditional Chinese herbal medicine that has been used in the treatment of liver diseases. However, its biological mechanisms remain elusive. The current study aimed to investigate the hepatoprotective effect of wedelolactone, a major coumarin ingredient of Eclipta prostrata L., on immune-mediated liver injury. Using the well-established animal model of Concanavalin A (ConA)-induced hepatitis (CIH), we found that pretreatment of mice with wedelolactone markedly reduced both the serum levels of transaminases and the severity of liver damage. We further investigated the mechanisms of the protective effect of wedelolactone. In mice treated with wedelolactone prior to the induction of CIH, increases of serum concentrations of tumor necrosis factor (TNF)-[Formula: see text], interferon (IFN)-[Formula: see text], and interleukin (IL)-6 were dramatically attenuated. Additionally, expressions of the interferon-inducible chemokine (C-X-C motif) ligand 10 gene CXCL10 and intercellular adhesion molecule 1 gene ICAM1 were lower in livers of the treated mice. Moreover, wedelolactone-treated CIH mice exhibited reduced leukocyte infiltration and T-cell activation in liver. Furthermore, wedelolactone suppressed the activity of nuclear factor-kappa B (NF-[Formula: see text]B), a critical transcriptional factor of the above-mentioned inflammatory cytokines by limiting the phosphorylation of I kappa B alpha (I[Formula: see text]B[Formula: see text] and p65. In conclusion, these findings demonstrate the inhibitory potential of wedelolactone in immune-mediated liver injury in vivo, and show that this protection is associated with modulation of the NF-[Formula: see text]B signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Concanavalina A/efeitos adversos , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Fitoterapia , Animais , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Quimiocina CXCL10/metabolismo , Cumarínicos/isolamento & purificação , Modelos Animais de Doenças , Eclipta/química , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interferon gama/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
13.
World Neurosurg ; 116: e258-e265, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29738858

RESUMO

OBJECTIVE: Neuroglobin (Ngb) has a high affinity for oxygen and helps prevent hypoxic-ischemic brain damage. In this study we analyzed the relationship between Ngb levels and clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Serum Ngb levels were measured in 58 patients with aSAH and 27 control individuals using the enzyme-linked immunosorbent assay. To continuously assess aSAH, we measured serum Ngb levels on days 1, 2, 3, 5, and 7 after aSAH. Clinical data were collected using the Hunt and Hess Scale, the Glasgow Coma Scale (GCS), the World Federation of Neurological Surgeons (WFNS) Scale, and the modified Fisher Scale. Clinical outcomes included 6-month mortality and 6-month unfavorable outcomes (modified Rankin Scale (mRS) score of 3-6). RESULTS: Serum Ngb levels increased after aSAH, peaked on day 2, and then gradually decreased. Serum Ngb levels on admission were higher in the patient group than in the control group (7.67 ± 2.56 ng/mL vs. 6.45 ± 0.88 ng/mL, P < 0.05). Multivariate logistic regression analysis indicated that serum Ngb levels on day 2 after aSAH were independently related to 6-month mortality (odds ratio [OR] = 0.265, 95% confidence interval [CI] = 0.094-0.747, P < 0.05) and 6-month unfavorable outcomes (OR = 1.919, 95% CI = 1.158-3.180, P < 0.05), and receiver operating characteristic curve analysis showed that serum Ngb levels on day 2 predicted 6-month mortality and 6-month unfavorable outcomes, with areas under the curve of 0.893 (P < 0.05; 95% CI, 0.812-0.974) and 0.818 (P < 0.05; 95% CI, 0.691-0.954), respectively, based on the best thresholds. CONCLUSIONS: Serum Ngb levels on day 2 after aSAH were strongly associated with poor outcomes in aSAH, suggesting that Ngb may be a novel biomarker for predicting poor outcomes in aSAH.


Assuntos
Proteínas do Tecido Nervoso/sangue , Avaliação de Resultados (Cuidados de Saúde) , Hemorragia Subaracnóidea/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Escala de Coma de Glasgow , Globinas , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglobina , Valor Preditivo dos Testes , Curva ROC , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/mortalidade , Fatores de Tempo
14.
J Cell Physiol ; 233(9): 6705-6713, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29319163

RESUMO

MicroRNAs (miRNAs) have been implicated as important regulators of carcinogenesis and tumor development. Recently, microRNA-22 (miR-22) has been reported to be a cancer-related miRNA in several types of tumors. In this study, we aimed to investigate the role of miR-22 in oral squamous cell carcinoma (OSCC). We found that miR-22 expression was significantly decreased in OSCC tissues compared with that in the adjacent noncancerous tissues. Furthermore, lentivirus-mediated miR-22 overexpression markedly reduced OSCC cell viability, migration and invasion, whereas miR-22 inhibitor promoted these parameters. Mechanistically, NLR family pyrin domain containing three (NLRP3) was identified as a direct target of miR-22. miR-22 expression was inversely correlated with NLRP3 expression both in OSCC tissues and cell lines. Moreover, overexpression of miR-22 in OSCC cells could reverse the tumor-promoting effect of the activated NLRP3 inflammasome and vice versus. Therefore, our results indicate that miR-22 may play a suppressive role in OSCC by targeting NLRP3, which offer new insights into the molecular mechanisms of the growth and metastasis of OSCC.

15.
Neurochem Int ; 112: 219-226, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28774717

RESUMO

Neuroglobin (Ngb) overexpression is considered as an intrinsic neuroprotective response. Therefore, exogenous Ngb increased in brain tissues has become a promising therapeutic strategy for neurological diseases. Previous studies demonstrated that transactivator of transcription (TAT) protein transduction domain was able to mediate synthetic Ngb entrance into neurons, and then protected brain from hypoxia-ischemic injury. However, the role of recombinant Ngb on early brain injury following subarachnoid hemorrhage (SAH) has not been elucidated. The objectives of this study were to investigate the expression of endogenous Ngb in brain using a rabbit model of SAH, and to verify whether TAT-Ngb fusion protein could be delivered into brain parenchyma, as well as to explore the neuroprotective effect of Ngb and its possible mechanisms. We found that Ngb expressions were up regulated in the transcript and protein levels in a similar time dependent manner after SAH as compared to the sham group. Moreover, TAT-Ngb fusion protein was successfully generated and transferred into brain neurons. Compared with the saline- and Ngb-treated group, neuronal viabilities and neurological outcomes were significantly improved 72 h post-SAH in the TAT-Ngb-treated group. Likewise, anti-apoptotic Bcl-2 protein was also elevated obviously. Conversely, pro-apoptotic factors including caspase 3, caspase 9 and Bax were greatly decreased after TAT-Ngb treatment. Our results suggest that Ngb plays a neuroprotective effect in rabbits suffering from SAH possibly through inhibiting the SAH-induced activation of mitochondria apoptotic pathway. Furthermore, TAT-mediated Ngb delivery into brain may be a promising therapeutic approach.

16.
Eur J Pharmacol ; 815: 282-289, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28935563

RESUMO

Oridonin, an active diterpeniod isolated from Rabdosia rubescens, has been reported for its anti-tumor activity on several cancers, however, its effect on oral squamous cell carcinoma (OSCC) remains unclear. In this study, we demonstrated for the first time that oridonin inhibited the growth of OSCC cells both in vitro and in vivo. Oridonin decreased the proliferation and clonal formation of cultured OSCC cells in a dose-dependent manner. Further study indicated that oridonin induced G2/M phase arrest in OSCC cells, which was associated with the downregulation of proteins related to G2/M transition including cdc25C, cdc2 and cyclin B1, as well as the upregulation of p53 and phosphorylated-cdc2. In addition, we discovered that oridonin induced OSCC cell apoptosis by activating the intrinsic apoptotic pathway, which was indicated by the increased expression of cleaved-caspase 3, cleaved-caspase 9 and proapoptotic protein Bax and reduced expression of caspase 9 and antiapoptotic protein Bcl-xl. Finally, oridonin suppressed the growth of OSCC in an xenograft mouse model. Immunohistochemical analysis showed a reduction of cyclin B1-positive cancer cells and an increase of TUNEL-positive cancer cells in oridonin-treated mice. Therefore, oridonin may be a potentially effective agent for the treatment of OSCC in future.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Diterpenos de Caurano/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Neoplasias Bucais/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Neuropsychiatr Dis Treat ; 13: 1771-1782, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28744127

RESUMO

Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH (P<0.05) and peaked at 48 hours after SAH (P<0.05). However, they were greatly reduced after treatment with necrostatin-1 (P<0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment (P<0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment.

18.
Neurosci Lett ; 656: 152-157, 2017 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-28729077

RESUMO

OBJECTIVE: The central mechanisms underlying postherpetic neuralgia (PHN) pain remains unknown. The primary purpose of this study was to identify microstructural white matter changes closely related to the PHN pain by means of diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) analysis. METHODS: DTI data of the brains were obtained from 8 PHN patients and 8 healthy controls (HC) that were matched in age, gender, and educational level. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were separately compared between the two groups using TBSS analysis to detect subtle microstructural changes. Partial correlation analyses were also conducted to evaluate the association between the altered DTI measures and clinical features. RESULTS: Average diffusion indices of white matter skeletons in the whole-brain showed no significant difference between the two groups. However, compared to the HC group, patients with PHN pain revealed reductions in localized FA and AD values in white matter underlying insula, occipital lobe, cerebellum, precentral gyrus, and many other regions, but without distinct change in regional MD and RD levels. In addition, decline of FA and AD values in patients represented significant negative correlations with PHN pain duration when the effect of VAS scores were excluded. CONCLUSION: The current study suggest that there exists altered microstructure integrity of white matter in multiple brain regions in patients with PHN, and these changes increase in size as the duration of the pain increases. These findings might provide a new insight into the mechanism of PHN pain in brain.


Assuntos
Neuralgia Pós-Herpética/patologia , Substância Branca/patologia , Adulto , Idoso , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Clin Neuropathol ; 36(5): 233-239, 2017 Sep/Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28737124

RESUMO

OBJECTIVE: To investigate the expression and distribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophic factor-3 (NT-3) in refractory epilepsy-associated type I focal cortical dysplasia (FCD I) and FCD IIA patients, and to explore their effects on pathogenesis of FCD I and FCD IIA. MATERIALS AND METHODS: 19 subjects who received surgery at the Department of Neurosurgery, First Affiliated Hospital, Fujian Medical University, China between June 2010 and May 2012, were enrolled in this study. They were pathologically diagnosed as FCD IIA (n = 7) and FCD I (n = 12) after surgery and were considered as two experimental groups. Temporal lobe samples of 10 subjects who had suffered craniocerebral injury but did not have nervous system disease were collected as a control group. Immunohistochemical methods and Western blot assays were used to detect the expression and distribution of BDNF, NGF, and NT-3 in temporal lobes, and differences in their expression and distribution were compared between experimental and control groups. RESULTS: BDNF expression was slightly higher in the FCD IIA group compared to that in the FCD I group and was significantly greater when compared with the control group. Compared with the control group, NGF and NT-3 expression was higher in the FCD groups. However, no significant difference was observed between the FCD IIA and FCD I group. CONCLUSION: Abnormal distribution and expression of BDNF, NGF, and NT-3 may play an important role in the mechanism of FCD I and FCD IIA-induced epilepsy.
.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/biossíntese , Malformações do Desenvolvimento Cortical/metabolismo , Fator de Crescimento Neural/biossíntese , Fatores de Crescimento Neural/biossíntese , Adolescente , Adulto , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/metabolismo , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical/complicações , Adulto Jovem
20.
J Clin Neurosci ; 44: 300-305, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28625587

RESUMO

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening hemorrhagic cerebrovascular disease. The concept of early brain injury (EBI), induced by sharply increased intracranial pressure (ICP) and low cerebral perfusion pressure (CPP) with cerebral global ischemia following aneurysm rupture, has been increasingly accepted. However, EBI has not been well studied partly due to lack of an ideal animal model. The purpose of this study was to establish a new aSAH model which can mimic the pathophysiological damage of EBI. Right frontal craniotomy was performed on New Zealand rabbits for placing a PE-50 tube at the suprasella cistern and an ICP probe at the anterior cranial fossa. The central ear artery was punctured and blood was shunted into the suprasellar cistern through the PE-50 tube. ICP, blood pressure, CPP and heart rate peri-aSAH were monitored throughout the experiments. The rabbits were examined for neurological deficits at 24h post-SAH. Brain coronal sections near the optic chiasma were assessed by HE and Cresyl violet staining. Three minutes after SAH induction, the ICP peaked to 61.7±9.8mmHg while CPP decreased to nadir 23.5±8.9mmHg, and both were gradually restored in 15min. At 24h post-SAH, significant neurological deficits were found in SAH rabbits as compared to the sham-operated animals. In addition, neuronal degeneration and loss were also detected. Our results indicate that a new rabbit model of aSAH with EBI is successfully established. Moreover, this model is controllable, economical, and no side-injury to the main artery.


Assuntos
Aneurisma Roto/patologia , Aneurisma Roto/fisiopatologia , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia , Aneurisma Roto/complicações , Aneurisma Roto/cirurgia , Animais , Artérias/patologia , Pressão Sanguínea/fisiologia , Encéfalo/cirurgia , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/cirurgia , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/fisiologia , Craniotomia , Modelos Animais de Doenças , Masculino , Monitorização Fisiológica , Degeneração Neural/complicações , Degeneração Neural/patologia , Coelhos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia
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