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1.
Pharmacol Res ; 122: 66-77, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28571892

RESUMO

Histone lysine specific demethylase 1 (LSD1) plays an important role in epigenetic modifications, and aberrant expression of LSD1 predicts tumor progression and poor prognosis in human esophageal cancers. In this study, a series of LSD1 inhibitors were synthesized and proved to be highly potent against human esophageal squamous cell carcinoma (ESCC). Our data showed that these LSD1 inhibitors selectively suppressed the viability of esophageal cancer cell line (EC-109) bearing overexpressed LSD1. Among these, compound LPE-1 (LSD1 IC50=0.336±0.003µM) significantly suppressed proliferation, induced apoptosis, arrested cell cycle of EC109 cells at G2/M phase, and caused changes of the associated protein markers correspondingly. We also found that compound LPE-1 potently inhibited the migration and invasion of EC-109 cells. Docking studies showed that the cyano group formed hydrogen bonds with Val811 and Thr810. Additionally, the thiophene moiety formed arene-H interaction with Trp761 residue. In vivo studies showed that compound LPE-1 inhibited tumor growth of xenograft models bearing EC-109 without obvious toxicity. Collectively, our findings indicate that LSD1 may be a potential therapeutic target in ESCC, and compound LPE-1 could serve as a lead compound for further development for anti-ESCC drug discovery.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Histona Desmetilases/antagonistas & inibidores , Pirimidinas/química , Pirimidinas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Esôfago/efeitos dos fármacos , Esôfago/metabolismo , Esôfago/patologia , Feminino , Histona Desmetilases/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Pirimidinas/uso terapêutico
2.
World J Surg Oncol ; 12: 196, 2014 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-24976133

RESUMO

Chondrosarcoma is a common malignant bone tumor, which accounts for 20% of all malignant bone tumors. It often occurs in the long bones, but the incidence of scapular chondrosarcoma is rare. Here, we describe a case of a large chondrosarcoma occurring in the scapula which was treated with Malawer limb salvage surgery. The patient retained considerable limb function after complete removal of the tumor tissue as assessed at the follow-up visit two years and ten months following surgery.


Assuntos
Neoplasias Ósseas/cirurgia , Condrossarcoma/cirurgia , Salvamento de Membro , Terapia de Salvação , Escápula/cirurgia , Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Escápula/patologia , Resultado do Tratamento
3.
Luminescence ; 29(2): 132-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23703841

RESUMO

Red-emitting Li(2)Sr(1-3x/2)Eux SiO4 0 ≤ x ≤ 0.5) phosphors were synthesized at 900 °C in air by a solid-state reaction. The synthesized phosphors were characterized by X-ray powder diffraction, photoluminescence (PL) excitation (PLE) and PL spectra. The results from the PLE spectra suggest that the strong 394 nm excitation peak associated with the (5) L6 state of Eu(3+) ions is of significance for near ultraviolet pumped white light-emitting diodes and solid-state lighting. It is also noted that the position of the charge transfer state of Eu(3+) ions shifts towards the higher energy side (blue shift) by increasing the content of Eu(3+) ions. The predominant emissions of Eu(3+) ions under 394 nm excitation are observed at 580, 593, 614, 656 and 708 nm, which are attributed to the (5) D0 → (7)FJ (J = 0, 1, 2, 3 and 4), respectively. The PL results reveal that the optimal content of the red-emitting Li2 Sr(1-3x/2)Eux SiO4 phosphors is x = 0.475. Simulation of the white light excited by 394 nm near ultraviolet light has also been carried out for its potential white light-emitting diode applications.


Assuntos
Európio/química , Lítio/química , Luminescência , Substâncias Luminescentes/análise , Substâncias Luminescentes/química , Silicatos/química , Estrôncio/química , Medições Luminescentes
4.
Zhonghua Nan Ke Xue ; 19(9): 811-4, 2013 Sep.
Artigo em Zh | MEDLINE | ID: mdl-24386860

RESUMO

OBJECTIVE: To investigate the roles of prostatic infarction, prostatic inflammation and the type of prostatic hyperplasia in acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH). METHODS: We retrospectively analyzed 102 cases of BPH, 49 complicated by AUR and the other 53 without AUR. We compared the incidences of prostatic infarction and prostatic inflammation, the types of prostatic hyperplasia, the patients' age, the level of prostate specific antigen (PSA), the prostate volume, and international prostate symptom score (IPSS) between the AUR and non-AUR groups. RESULTS: The PSA level was significantly increased in the AUR group as compared with the non-AUR group (P < 0.05). There were no statistically significant differences between the two groups in the mean age, prostate volume and IPSS (P > 0.05). The type of prostatic hyperplasia showed no correlation with AUR. The incidence rate of AUR was 5.620 and 2.326 times higher in the BPH patients with prostatic infarction and prostatic inflammation respectively than in those without (P < 0.05). CONCLUSION: Prostatic infarction and prostatic inflammation are important risk factors of AUR in BPH patients.


Assuntos
Próstata/patologia , Hiperplasia Prostática/patologia , Retenção Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/química , Hiperplasia Prostática/complicações , Estudos Retrospectivos , Fatores de Risco , Retenção Urinária/complicações
5.
J Agric Food Chem ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37917162

RESUMO

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

6.
Oxid Med Cell Longev ; 2022: 5098358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035220

RESUMO

Bone metabolism occurs in the entire life of an individual and is required for maintaining skeletal homeostasis. The imbalance between osteogenesis and osteoclastogenesis eventually leads to osteoporosis. Oxidative stress is considered a major cause of bone homeostasis disorder, and relieving excessive oxidative stress in bone mesenchymal stem cells (BMSCs) is a potential treatment strategy for osteoporosis. Carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide (CO), possesses antioxidation, antiapoptosis, and anti-inflammatory properties. In our study, we found that CORM-3 could reduce reactive oxygen species (ROS) accumulation and prevent mitochondrial dysfunction thereby restoring the osteogenic potential of the BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The action of CORM-3 was preliminarily considered the consequence of Nrf2/HO-1 axis activation. In addition, CORM-3 inhibited osteoclast formation in mouse primary bone marrow monocytes (BMMs) by inhibiting H2O2-induced polarization of M1 macrophages and endowing macrophages with M2 polarizating ability. Rat models further demonstrated that CORM-3 treatment could restore bone mass and enhance the expression of Nrf2 and osteogenic markers in the distal femurs. In summary, CORM-3 is a potential therapeutic agent for the treatment of osteoporosis.


Assuntos
Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Compostos Organometálicos , Osteoporose , Animais , Monóxido de Carbono , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Organometálicos/metabolismo , Estresse Oxidativo , Ratos , Transdução de Sinais
7.
Br J Radiol ; 95(1140): 20220368, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36169239

RESUMO

OBJECTIVES: Accurate preoperative diagnosis of small cell neuroendocrine cancer of the cervix (SCNECC) is crucial for establishing the best treatment plan. This study aimed to develop an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information. METHODS: A total of 105 pathologically confirmed cervical cancer patients (35 SCNECC, 70 non-SCNECC) from multiple centres with complete clinical and MR records were included. Whole lesion histogram analysis of the ADC was performed. Multivariate logistic regression analysis was used to develop diagnostic models based on clinical, morphological, and histogram data. The predictive performance in terms of discrimination, calibration, and clinical usefulness of the different models was assessed. A nomogram for preoperatively discriminating SCNECC was developed from the combined model. RESULTS: In preoperative SCNECC diagnosis, the combined model, which had a diagnostic AUC (area under the curve) of 0.937 (95% CI: 0.887-0.987), outperformed the clinical-morphological model, which had an AUC of 0.869 (CI: 0.788-0.949), and the histogram model, which had an AUC of 0.872 (CI: 0.792-0.951). The calibration curve and decision curve analyses suggest that the combined model achieved good fitting and clinical utility. CONCLUSIONS: Non-invasive preoperative diagnosis of SCNECC can be achieved with high accuracy by integrating clinical, MR morphological, and ADC histogram features. The nomogram derived from the combined model can provide an easy-to-use clinical preoperative diagnostic tool for SCNECC. ADVANCES IN KNOWLEDGE: It is clear that the therapeutic strategies for SCNECC are different from those for other pathological types of cervical cancer according to V 1.2021 of the NCCN clinical practice guidelines in oncology for cervical cancer. This research developed an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information.


Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Neoplasias do Colo do Útero , Feminino , Humanos , Nomogramas , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Colo do Útero/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/cirurgia , Estudos Retrospectivos
8.
ACS Appl Mater Interfaces ; 12(20): 23554-23564, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32338501

RESUMO

The recently proposed digital reconfigurable metasurfaces make it possible to manipulate electromagnetic (EM) waves flexibly. However, most existing reconfigurable metasurfaces can only exhibit a relatively single performance in the spatial domain. Here, we propose a general frequency- and spatial-domain reconfigurable metasurface (FSRM) that can manipulate the EM waves and realize reconfigurable functions in multifrequency bands. In the frequency domain, FSRM can convert different linearly polarized (LP) incident waves into left- and right-hand circularly polarized reflected waves, in which PIN diodes are used to switch the polarization conversions in different frequency bands. When the polarization direction of the incident LP wave is 45° from the +x-axis, the FSRM modulates the incident waves as a 1-bit programmable metasurface in the spatial domain. Two-dimensional beam scanning, vortex beams with orbital angular momentums, and specific beams with desired transmission directions are demonstrated via real-time adjustment of the digital coding state. To validate the modulation methodology, an FSRM prototype is fabricated and measured, which could respond to different functions for different polarization incidences. The measured results agree well with the theoretical analyses. The proposed FSRM will provide new opportunities for smart material designs.

9.
Saudi J Biol Sci ; 25(6): 1140-1145, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30174514

RESUMO

In this study, we mainly aimed at developing the Ifosfamide-loaded-lipid-core nanocapsules (IFS-LNC) to increase the therapeutic efficacy in osteosarcoma. The nanoparticle was prepared and evaluated in terms of physical, chemical and biological parameters. The lipid-core-nanocapsules were nanosized with narrow particle size distribution and exhibited a high loading capacity. The LNC displayed a sustained release profile of the drug suggesting its potential application in biomedical field and prolonged anticancer therapy. The LNC showed an endocytosis-mediated cellular uptake in MG63 cancer cells which may lead to an accelerated disruption of the acidic endolysosomal vesicles with release of IFS into the cytoplasm. Specifically, IFS-LNC exhibited a significantly higher cytotoxicity than free IFS used at the same concentration. The indiscriminate ability of the drug-loaded formulation increased the apoptosis of cancer cells by increasing the expression levels of caspase-3 and caspase-9 in MG63 cells. Overall, nanoparticulate formulations of Ifosfamide enhanced the therapeutic efficacy in osteosarcoma.

10.
Eur J Med Chem ; 143: 1535-1542, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29126726

RESUMO

ABCB1-mediated multidrug resistance (MDR) is a principal obstacle for successful cancer chemotherapy. A series of pyrimidine-based hybrid molecules containing 1,2,3-triazole moiety were evaluated for their reversal activities against MDR. The majority of target compounds displayed moderate to great reversal potency. Among these compounds, compound 25 displayed the most potent reversal activity, about 7-fold more potent than Verapamil (VRP). Further mechanism studies revealed that compound 25 could obviously reverse paclitaxel (PTX) resistance in SW620/AD300 cells by increasing accumulation and extending maintenance of PTX. Our findings indicate that the 1,2,3-triazole-pyrimidine-based derivatives may serve as an interesting lead for the development of new potent and efficacious ABCB1-dependent MDR modulators.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Pirimidinas/farmacologia , Triazóis/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Pirimidinas/química , Relação Estrutura-Atividade , Triazóis/química , Células Tumorais Cultivadas
11.
Medchemcomm ; 8(12): 2173-2180, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108734

RESUMO

A series of novel thiosemicarbazone derivatives were synthesized and evaluated for their antiproliferative activity against several selected tumor cell lines of different origins using the MTT assay. The preliminary results indicated that the MGC-803 cell line was remarkably sensitive to all the synthesized compounds. Among this series, compound 5n showed the best inhibitory activity with an IC50 value of 0.93 µM (about 10-fold more potent than 3-AP) against MGC-803. Further mechanism studies revealed that compound 5n could obviously inhibit the proliferation of MGC-803 cells by inducing apoptosis and arresting the cell cycle at the S phase. Compound 5n also showed marked inhibition of cell migration and invasion, without significant cytotoxicity against gastric epithelial immortalized GES-1 cells.

12.
Clin Drug Investig ; 26(6): 341-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17163268

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases, with acute ST-segment elevation myocardial infarction (STEMI) showing a higher mortality rate than non-ST-segment elevation myocardial infarction (NSTEMI). There is evidence that low-molecular-weight heparin (LMWH) shows greater efficacy than unfractionated heparin (UFH). This open-label, single-centre, randomised study was conducted to compare the efficacy and safety of parnaparin sodium, a LMWH, with UFH in patients with STEMI. PATIENTS AND METHODS: Patients with STEMI were randomised to receive either parnaparin sodium (4250IU aXa subcutaneously every 12 hours for 7 days, initiated 12 hours after thrombolysis) or UFH (100 U/kg intravenous bolus, initiated 12 hours after thrombolytic therapy, followed by 1000 U/hour as a continuous infusion for 3 days, then 7500U subcutaneously every 12 hours for 4 days). Patients were followed up for 45 days (> or =14 days in hospital). RESULTS: In total, 186 patients were randomised to receive parnaparin sodium (n = 96) or UFH (n = 90). A significantly greater reduction in the composite primary endpoint (sum of all deaths, first occurrence of recurrent MI, and first occurrence of emergency revascularisation) was seen with parnaparin sodium compared with UFH at day 45 (27.08% vs 42.22%; p = 0.03). A lower incidence of composite endpoint was seen as early as day 2 with parnaparin sodium, but this did not reach significance versus UFH. The rate of individual endpoint events (death, first occurrence of non-fatal recurrent MI and first occurrence of emergency revascularisation) was lower in the parnaparin sodium group than the UFH group at 2, 7, 14 and 45 days, but the differences were not statistically significant. At day 7, the incidences of any bleeding and heparin-induced thrombocytopenia were also lower in the parnaparin sodium group compared with the UFH group (3.13% vs 10.0%; p = 0.06 and 0% vs 3.33%; p = 0.07, respectively). CONCLUSION: The results of this study indicate that parnaparin sodium is more effective than UFH in reducing composite cardiac events in patients with STEMI following thrombolytic therapy. There was also a lower incidence of bleeding and heparin-induced thrombocytopenia with parnaparin sodium than with UFH. In view of these findings, parnaparin sodium represents an effective, convenient and well tolerated alternative to UFH.


Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Esquema de Medicação , Quimioterapia Combinada , Eletrocardiografia , Feminino , Hemorragia/induzido quimicamente , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Tempo de Tromboplastina Parcial/métodos , Contagem de Plaquetas/métodos , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Tomógrafos Computadorizados , Resultado do Tratamento
13.
Virus Res ; 220: 172-8, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27157859

RESUMO

Multigene-armed oncolytic adenoviruses are capable of efficiently generating a productive antitumor immune response. The chemokine (C-C motif) ligand 21 (CCL21) binds to CCR7 on naïve T cells and dendritic cells (DCs) to promote their chemoattraction to the tumor and resultant antitumor activity. Interleukin 21 (IL21) promotes survival of naïve T cells while maintaining their CCR7 surface expression, which increases their capacity to transmigrate in response to CCL21 chemoattraction. IL21 is also involved in NK cell differentiation and B cell activation and proliferation. The generation of effective antitumor immune responses is a complex process dependent upon coordinated interactions of various subsets of effector cells. Using the AdEasy system, we aimed to construct an oncolytic adenovirus co-expressing CCL21 and IL21 that could selectively replicate in TERTp-positive tumor cells (Ad-CCL21-IL21 virus). The E1A promoter of these oncolytic adenoviruses was replaced by telomerase reverse transcriptase promoter (TERTp). Ad-CCL21-IL21 was constructed from three plasmids, pGTE-IL21, pShuttle-CMV-CCL21 and AdEasy-1 and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Our results showed that our targeted and armed oncolytic adenoviruses Ad-CCL21-IL21 can induce apoptosis in TERTp-positive tumor cells to give rise to viral propagation, in a dose-dependent manner. Importantly, we confirm that these modified oncolytic adenoviruses do not replicate efficiently in normal cells even under high viral loads. Additionally, we investigate the role of Ad-CCL21-IL21 in inducing antitumor activity and tumor specific cytotoxicity of CTLs in vitro. This study suggests that Ad-CCL21-IL21 is a promising targeted tumor-specific oncolytic adenovirus.


Assuntos
Adenoviridae/genética , Proteínas E1A de Adenovirus/genética , Quimiocina CCL21/genética , Interleucinas/genética , Vírus Oncolíticos/genética , Telomerase/genética , Adenoviridae/imunologia , Proteínas E1A de Adenovirus/imunologia , Células CACO-2 , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CCL21/imunologia , Técnicas de Cocultura , Células Epiteliais/citologia , Células Epiteliais/imunologia , Escherichia coli/genética , Escherichia coli/metabolismo , Células HEK293 , Células HT29 , Células HeLa , Recombinação Homóloga , Humanos , Interleucinas/imunologia , Masculino , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/imunologia , Plasmídeos/química , Plasmídeos/imunologia , Próstata/citologia , Próstata/imunologia , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Células THP-1 , Telomerase/imunologia
14.
Neural Regen Res ; 10(6): 996-1002, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26199620

RESUMO

Therapeutic strategies for neurological deficits and for promoting nerve regeneration after peripheral nerve injuries have received much focus in clinical research. Advances in basic research in recent years have increased our understanding of the anatomy of peripheral nerves and the importance of the microenvironment. Various new intervention methods have been developed, but with varying effectiveness. In the present study, we selected 911 papers on different repair methods for peripheral nerve injury from the Web of Science and indexed in the Science Citation Index from 2010 to 2014. We quantitatively examine new repair methods and strategies using bibliometrics, and we discuss the present state of knowledge and the problems and prospects of various repair methods, including nerve transfer, neural transplantation, tissue engineering and genetic engineering. Our findings should help in the study and development of repair methods for peripheral nerve injury.

15.
Int J Clin Exp Med ; 8(9): 15383-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26629027

RESUMO

PURPOSE: Mild cognitive impairment is common in Parkinson's disease, but the underlying pathological mechanism has not been fully understood. To examine the gray matter changes in patients with Parkinson's disease and those with mild cognitive impairment (MCI) using voxel based Morphometry (VBM). METHODS: Magnetic resonance images were obtained from 35 patients with PD and 20 age and sex-matched healthy control subjects. In the PD group, 14 subjects had no MCI and 21 had MCI. MRI 3D structural images were acquired and analyzed by means of the optimized VBM procedure with Statistical Parametric Mapping (SPM5). RESULTS: Widespread areas of cortical atrophy were found in patients with PD compared with normal controls (in both temporal, occipital, parietal, frontal lobes and right limbic lobes, posterior lobes of the cerebellum and left caudate nucleus). Gray matter reductions were found in bilateral fusiform gyrus and lingual gyrus, left anterior cingulate cortex and insula, and right superior temporal gyrus, orbitofrontal cortex, central gyrus and precuneus in patients with PD with MCI compared with normal controls. Inpatients with PD with MCI, areas of reduced gray matter were found in both precentral gyrus and middle temporal gyrus, right cuneus, precuneus, and orbitofrontal cortex, and left fusiform gyrus compared with those without MCI. CONCLUSIONS: These findings suggest that PD is associated with the gray matter atrophy in the neocortical areas, and that cognitive impairment in patients with PD may be associated with gray matter changes in the parieto-occipital association cortex, right orbitofrontal cortex, and middle temporal gyrus.

16.
Int Immunopharmacol ; 28(1): 487-93, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26208317

RESUMO

Conditionally replicating adenoviruses (CRAds) selectively replicate in cancer cells and induce cell lysis, which represents a potential platform for cancer immunotherapy. The chemokine CCL20 exerts antitumor activity via chemoattraction of immature dendritic cells (DCs) and lymphocytes. However, the activation and maturation status of DCs is a limiting factor in the DCs -based immunity response. CD40L induces the phenotypic maturation of DCs, mediates DCs cytokine secretion, and increases the expression of FasL, which mediates apoptosis. We constructed a CCL20/CD40L co-expression CRAds (Ad-CCL20-CD40L) based on the AdEasy system. Ad-CCL20-CD40L was constructed from three plasmids, pGTE-CD40L, pShuttle-CMV-CCL20 and AdEasy-1, and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Ad-CCL20-CD40L selectively replicates in TERT-positive tumor cells because the pGTE-CD40L plasmid contains the telomerase reverse transcriptase promoter (TERTp). Our results showed that Ad-CCL20-CD40L induced oncolytic effects and tumor-specific cytotoxicity of cytotoxic T lymphocytes (CTLs) in vitro. This study suggests that Ad-CCL20-CD40L can induce the antitumor immune response and that this platform can be modified to generate novel CRAds with other transgenes.


Assuntos
Adenoviridae/genética , Ligante de CD40/genética , Quimiocina CCL20/genética , Vírus Oncolíticos/genética , Telomerase/genética , Linhagem Celular Tumoral , Terapia Genética , Humanos , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia
17.
Sheng Li Xue Bao ; 54(2): 165-70, 2002 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-11973599

RESUMO

Proliferation of vascular smooth muscle cells (VSMCs) is often accompanied by changes in intracellular actin distribution. The changes are controlled by the signal transduction pathways of protein kinase C/mitogenic activated protein kinase (PKC-MAPK), but the mechanism is unclear. In order to study the effect of insulin on the intracellular signal transduction (PKC-MAPK) probably involved in the modulation of proliferation and redistribution of actins in the VSMCs, the DNA synthesis, MAPK activities and its gene expression, and the redistribution of intracellular actins were investigated in the isolated VSMCs of SHR pretreated with PKC inhibitor and/or insulin, respectively. We found that insulin treatment resulted in proliferation of the VSMCs and an increase in [(3)H] TdR incorporation. Meanwhile, the activities and expression of MAPK increased significantly compared to the control group. These effects of insulin were blocked by PKC inhibitor. In addition, insulin caused a redistribution of the intracellular actins in VSMCs, which was also inhibited by PKC inhibitor. It is, therefore, suggested that these effects of insulin on VSMCs proliferation and distribution of the intracellular actins may be mediated by the MAPK signal transduction pathway.


Assuntos
Actinas/metabolismo , Insulina/farmacologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Proteína Quinase C/fisiologia , Animais , Divisão Celular/efeitos dos fármacos , Técnicas In Vitro , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/metabolismo , Ratos , Ratos Endogâmicos SHR , Distribuição Tecidual
18.
Di Yi Jun Yi Da Xue Xue Bao ; 24(1): 81-4, 2004 Jan.
Artigo em Zh | MEDLINE | ID: mdl-14724106

RESUMO

OBJECTIVE: To compare the efficacy and safety of unfractionated heparin with a low-molecular-weight heparin (parnaparin) in the management of anticoagulation following thrombolytic therapy for acute ST-segment elevation myocardial infarction. METHODS: One hundred and eighty-six patients with acute ST-segment elevation myocardial infarction undergoing thrombolytic therapy were randomly assigned to receive either unfractionated heparin (100 U/kg x b.w. intravenous bolus, 1,000 U/h continuous infusion for 3 days just 12 h after thrombolysis to maintain the activated partial thromboplastin time at 1.5 to 2.0 times as normal, then subcutaneous 7500 U every 12 h for 4 days, n=90) or parnaparin (0.4 ml subcutaneously every 12 h for 7 days 12 h after thrombolysis, n=96) in conjunction with routine therapy. The patients enrolled stayed in hospital for at least 14 days and were followed for 45 days after admission into the hospital. RESULTS: The composite triple end-point (death, recurrent myocardial infarction, emergency revascularization assessed at 2, 7, 14, 45 days) was significantly reduced in patients receiving parnaparin 42.22% vs 37.08%, P=0.03 . Compared with unfractionated heparin group, the incidences of hemorrhage 10.00% vs 3.13%, P=0.06 and heparin-induced thrombocytopenia (3.33% vs 0, P=0.07) were also lower in parnaparin group. CONCLUSION: Parnaprin is more effective in reducing composite cardiac events, hemorrhage and heparin-induced thrombocytopenia at least in 45 days as compared with unfractionated heparin during anticoagulation following thrombolytic therapy for acute ST-segment elevation myocardial infarction.


Assuntos
Eletrocardiografia , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia
19.
J Cancer Res Ther ; 10(4): 927-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25579530

RESUMO

OBJECTIVE: This study evaluates the magnetic resonance imaging (MRI) manifestation of intradural extramedullary (IDEM) tumors to improve the imaging diagnostic level. MATERIALS AND METHODS: From January 2005 to December 2012, a retrospective analysis of the MRI examination was performed on 108 patients with IDEM tumors confirmed by surgical pathology postoperatively in our hospital. According to the pathological classification; the gender, age, location, size, foraminal state extension, signal intensity (compared with the spinal cord), and enhancement were recorded and statistically analyzed. RESULTS: A total of 108 cases (111 lesions) were reported; 69 (70 lesions), 31 (31 lesions), three (five lesions), four (four lesions), and one (one lesion) of which were schwannoma, meningioma, neurofibroma, teratoma, and metastatic tumor, respectively. MRI manifestations of different IDEM tumors have certain specificities. CONCLUSION: MRI is the preferred examination method for to diagnose IDEM tumors and provide a reliable imaging basis for clinical treatment and prognosis judgment.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Neurilemoma/diagnóstico , Neurofibroma/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Teratoma/diagnóstico , Adolescente , Adulto , Idoso , Artefatos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Neurilemoma/patologia , Neurofibroma/patologia , Prognóstico , Estudos Retrospectivos , Medula Espinal/patologia , Neoplasias da Medula Espinal/patologia , Teratoma/patologia , Adulto Jovem
20.
Oncol Lett ; 7(5): 1669-1672, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24765198

RESUMO

The aim of this study was to investigate the microsurgical techniques of hemilaminectomy, used in the excision of intradural extramedullary (IDEM) tumors, and to illustrate its clinical effects. Clinical data obtained from 16 patients (seven males, nine females) with IDEM tumors, which were treated at the China-Japan Union Hospital between January 2009 and December 2011, were retrospectively analyzed. The mean age of patients was 49 years, ranging from 34-72 years. The IDEM tumors were located cervically in three patients, thoracically in four patients and at the thoracico-lumbar level in nine patients. Fourteen patients underwent hemilaminectomy, while two patients were treated with laminectomy during surgery. The clinical effect of hemilaminectomy was evaluated based on Frankel grade. The mean bleeding volume was 300 ml (range, 150-500 ml) and the mean duration of surgery was 140 min (range, 90-200 min). The maximum and minimum tumor volumes were 4×1.5×1.5 cm and 1.5×1.0×1.0 cm, respectively. Neurinoma was evident in 11 patients, meningioma in four cases and neurofibroma in one case. Three cases improved from Frankel grade B to C, five cases improved from grade C to D and seven cases improved from grade D to grade E. All patients were followed up for a period of 6-40 months, with a mean follow-up time of 23.7 months. None of the patients exhibited tumor recurrence or spinal instability. The mean bleeding volume of patients that underwent hemilaminectomy and laminectomy was 275 and 475 ml, respectively. The advantages of hemilaminectomy are minor invasion, less bleeding and retention of spinal stability. In general, hemilaminectomy for the excision of IDEM tumors has a satisfactory outcome.

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