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1.
Front Hum Neurosci ; 15: 777043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744673

RESUMO

Introduction: Cognitive decline is the core schizophrenia symptom, which is now well accepted. Holding a role in various aspects of cognition, lentiform nucleus (putamen and globus pallidus) dysfunction contributes to the psychopathology of this disease. However, the effects of lentiform nucleus function on cognitive impairments in schizophrenia are yet to be investigated. Objectives: We aim to detect the fractional amplitude of low-frequency fluctuation (fALFF) alterations in patients with schizophrenia, and examine how their behavior correlates in relation to the cognitive impairments of the patients. Methods: All participants underwent magnetic resonance imaging (MRI) and cognitive assessment (digit span and digit symbol coding tests). Screening of brain regions with significant changes in fALFF values was based on analysis of the whole brain. The data were analyzed between Jun 2020 and Mar 2021. There were no interventions beyond the routine therapy determined by their clinicians on the basis of standard clinical practice. Results: There were 136 patients (75 men and 61 women, 24.1 ± 7.4 years old) and 146 healthy controls (82 men and 64 women, 24.2 ± 5.2 years old) involved in the experiments seriatim. Patients with schizophrenia exhibited decreased raw scores in cognitive tests (p < 0.001) and increased fALFF in the bilateral lentiform nuclei (left: 67 voxels; x = -24, y = -6, z = 3; peak t-value = 6.90; right: 16 voxels; x = 18, y = 0, z = 3; peak t-value = 6.36). The fALFF values in the bilateral lentiform nuclei were positively correlated with digit span-backward test scores (left: r = 0.193, p = 0.027; right: r = 0.190, p = 0.030), and the right lentiform nucleus was positively correlated with digit symbol coding scores (r = 0.209, p = 0.016). Conclusion: This study demonstrates that cognitive impairments in schizophrenia are associated with lentiform nucleus function as revealed by MRI, involving working memory and processing speed.

2.
J Asian Nat Prod Res ; : 1-10, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042537

RESUMO

In our previous studies, a kind of novel benzenesulfonamides was found to be a candidate insecticidal compounds. It was shown that propargyloxy and sulfonamide groups are pharmacodynamic groups. One hundred and twenty-six (126) naphthalenesulfonamides derivatives with propargyloxy functionality were designed and synthesized, and their insecticidal activities were determined. Some of them showed outstanding activity, with LC50 values as low as 0.202 mg ml-1, much lower than that of the positive control celangulin V (23.9 mg ml-1). In addition, the structure-activity relationships were discussed, and molecular docking was used to verify the binding mode of the compound and the target receptor.

3.
BMJ Open ; 11(4): e043415, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795300

RESUMO

OBJECTIVES: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT). DESIGN: Analysis of a multicentre prospective registry. SETTING: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively. PARTICIPANTS: 224 patients with AIS were treated by MT. RESULTS: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality. CONCLUSIONS: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052).


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Isquemia Encefálica/terapia , Humanos , Sistema de Registros , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Trombectomia , Resultado do Tratamento
4.
J Neurol ; 268(7): 2560-2569, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33555418

RESUMO

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.


Assuntos
Isquemia Encefálica , Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
5.
J Cell Physiol ; 236(2): 1148-1157, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32686156

RESUMO

Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.


Assuntos
Proteína 5 Relacionada à Autofagia/genética , Benzodioxóis/farmacologia , Caspase 7/genética , Inibidores Enzimáticos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/farmacologia , Quinases da Família src/genética , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Proteínas Fúngicas/química , Proteínas Fúngicas/farmacologia , Ganoderma/química , Humanos , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Mutações Sintéticas Letais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/antagonistas & inibidores
6.
Curr Neurovasc Res ; 17(4): 464-470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32748746

RESUMO

OBJECTIVE: This study aims to explore in detail, the mechanism of the carbon monoxide releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation brain injury (RBI). METHODS: The brain injury models of BV2 cells and Balb/C mice were established and randomly divided into three groups: the normal control group (CON), the single radiation group (RAD), and the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to observe the effects on activation of the MG. The expressions of inflammatory factors, such as intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI) model were detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris water maze was used to assess the spatial learning and memory of the mice. RESULTS: Within 48 h after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might alleviate MG-mediated neuronal apoptosis and promote neural regeneration in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase the swimming distance and platform-stay time of the mice in the target platform quadrant after radiation. CONCLUSION: CORM-3 could effectively improve the inflammatory response induced by activation of the MG, reduce neuronal apoptosis, promote neural regeneration, and improve the learning and memory performance of mice after radiation.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Memória/efeitos da radiação , Microglia/efeitos da radiação , Neurônios/efeitos da radiação , Compostos Organometálicos/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Animais , Linhagem Celular , Técnicas de Cocultura , Hipocampo/efeitos dos fármacos , Hipocampo/efeitos da radiação , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Compostos Organometálicos/uso terapêutico
7.
Front Immunol ; 11: 848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536911

RESUMO

To investigate the fine epitope(s) of anti-C1q A08 antibodies and their roles in complement activation in lupus nephritis, C1q A08 and related peptides with various amino acid sequences around A08 were synthesized. Anti-C1q A08 antibodies from 10 lupus nephritis patients were purified from plasmapheresis samples, and four monoclonal antibodies against C1q A08 were screened and identified from mouse hybridoma cells, to study the fine epitope(s) of C1q A08 using ELISA and Biolayer Interferometry (BLI). The biofunction of anti-C1q A08 antibodies for complement classical pathway activation was investigated by C3 activation assay. Anti-C1q A08 antibodies and anti-C1q antibodies were also detected in the sera of female BALB/C mice immunized by C1q A08 peptides. None of the anti-C1q A08 antibodies, which were affinity purified from the 10 lupus nephritis patients, could bind intact C1q coated on microtitre plates, neither could the anti-C1q antibodies bind to C1q A08 peptides coupled on resin, indicating that the human anti-C1q antibodies and anti-C1q A08 antibodies may recognize different epitopes of C1q. One of the four C1q A08 mAbs (32-4) bound to the six amino acids of N-terminus of C1q A08, while another C1q A08 mAb (17-9) bound to eight or 10 amino acids of C-terminus of A08. The third and fourth C1q A08 mAb (1A12 and 4B11) bound to the whole sequence of A08. Only 32-4 mAb bound to the intact C1q coating on an ELISA plate, whereas 17-9 mAb, 1A12 mAb, and 4B11 mAb could not. However, using a BLI assay, 17-9 mAb, 1A12 mAb, and 4B11 mAb, but not 32-4 mAb, could bind to intact C1q. Furthermore, 1A12 mAb and 4B11 mAb, but not 32-4 and 17-9 mAb, could inhibit the activation of complement classical pathway. Anti-C1q A08 antibodies were detected in all the female BALB/C mice in the experimental group but not in the control group. Two out of six in the experimental group developed anti-C1q antibodies. C1q A08 is a half-cryptic epitope of C1q involving N-terminal six amino acids of C1q A08, and this is important to the activation of a complement classical pathway, and some anti-C1q A08 antibodies were able to prevent this process. Epitope spreading of C1q occurred in the mice immunized with C1q A08 peptides.


Assuntos
Autoanticorpos/imunologia , Ativação do Complemento , Complemento C1q/química , Complemento C1q/imunologia , Via Clássica do Complemento , Epitopos/imunologia , Nefrite Lúpica/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Afinidade de Anticorpos , Complemento C1q/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hibridomas/imunologia , Hibridomas/metabolismo , Imunização/métodos , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C
8.
Br J Cancer ; 123(3): 449-458, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32448867

RESUMO

BACKGROUND: Adaptive drug resistance is an unfavourable prognostic factor in cancer therapy. Pemetrexed-resistant lung cancer cells possess high-metastatic ability via ERK-ZEB1 pathway-activated epithelial-mesenchymal transition. GMI is a fungal immunomodulatory protein that suppresses the survival of several cancer cells. METHODS: Cell viability was analysed by MTT, clonogenic, tumour spheroid, and cancer stem cell sphere assays. Western blot assay was performed to detect the protein expression. Chemical inhibitors and ATG5 shRNA were used to inhibit autophagy. Tumour growth was investigated using xenograft mouse model. RESULTS: GMI decreased the viability with short- and long-term effects and induced autophagy but not apoptosis in A549/A400 cells. GMI downregulated the expression levels of CD133, CD44, NANOG and OCT4. GMI induces the protein degradation of CD133 via autophagy. CD133 silencing decreased the survival and proliferation of A549/A400 cells. GMI suppressed the growth and CD133 expression of A549/A400 xenograft tumour. CONCLUSIONS: This study is the first to reveal the novel function of GMI in eliciting cytotoxic effect and inhibiting CD133 expression in pemetrexed-resistant lung cancer cells via autophagy. Our finding provides evidence that CD133 is a potential target for cancer therapy.


Assuntos
Antígeno AC133/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ganoderma/metabolismo , Fatores Imunológicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Antígeno AC133/genética , Animais , Autofagia , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas Fúngicas/administração & dosagem , Proteínas Fúngicas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Pemetrexede/administração & dosagem , Pemetrexede/farmacologia , Proteólise , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Asian J Psychiatr ; 51: 101992, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32145674

RESUMO

AIM: The aim of this study was to determine the efficacy and safety of cranial electrotherapy stimulation (CES) as an add-on treatment for TD. METHODS: A randomized, double-blind, sham-controlled trial was conducted at an outpatient, single-center academic setting. A total of 62 patients aged 6-17 years with TD and lack of clinical response to 4 weeks' pharmacotherapy were enrolled. Patients were divided randomly into 2 groups and given 4 weeks' treatment, including 30 min sessions of active CES (500 µA-2 mA) or sham CES (lower than 100 µA) per day for 40 d on weekdays. Change in Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression-severity of illness-severity (CGI-S) and Hamilton Anxiety Scale-14 items (HAMA-14) were performed at baseline, week 2, week 4. Adverse events (AEs) were also evaluated. RESULTS: 53 patients (34 males and 9 females) completed the trial, including 29 in the active CES group and 24 in the sham CES group. Both groups showed clinical improvement in tic severities compared to baseline respectively at week 4. Participants receiving active CES showed a reduction of 31.66 % in YGTSS score, compared with 23.96 % in participants in sham CES group, resulting in no significant difference between the two groups (t = 1.54, p = 0.13). CONCLUSION: Four-week's treatment of CES for children and adolescents with TD is effective and safe, but the improvement for tic severity may be related to placebo effect.


Assuntos
Terapia por Estimulação Elétrica , Transtornos de Tique , Síndrome de Tourette , Adolescente , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Transtornos de Tique/terapia , Síndrome de Tourette/terapia , Resultado do Tratamento
10.
Nat Prod Res ; 34(11): 1521-1527, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30445866

RESUMO

A new ester (1) and a terpenoid (2) were isolated from the dried whole plant of Disporopsis aspersa (HUA) ENGL. ex DIELS for the first time and their structures were elucidated, as well as their biological activities are described. The two compounds all showed good antifungal activities, especially furanone (2) exhibited better antifungal activity against Pseudoperonospora cubensis and Phytophthora infestans with EC50 value of 22.82, 18.90 µg/mL, respectively. Compound 1 exhibited a significant promotion on the neurite outgrowth in NGF-induced PC-12 cells, and moderate inhibition on the NO production induced by lipopolysaccharide (LPS) in BV-2 microglial cells.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Antifúngicos/isolamento & purificação , Asparagaceae/química , Crescimento Neuronal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Ésteres/isolamento & purificação , Ésteres/farmacologia , Microglia/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Células PC12/efeitos dos fármacos , Células PC12/ultraestrutura , Phytophthora infestans/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Terpenos/isolamento & purificação , Terpenos/farmacologia
11.
Oncol Lett ; 18(4): 4328-4336, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579427

RESUMO

The aim of the present study was to examine the role of ABT-737, an inhibitor of B-cell lymphoma 2 (Bcl-2), in enhancing the effect of irradiation on uterine cervical cancer. Based on The Cancer Genomic Atlas (TCGA), Bcl-2 mRNA expression was associated with the Tumor-Node-Metastasis stage of cervical cancer. Therefore, it was hypothesized that Bcl-2 inhibition may decrease the progression of cervical cancer. ABT-737 was added to irradiation treatment to evaluate its effectiveness in inhibiting cancer cell progression. SiHa and CaSki cervical cancer cells were selected for in vitro assays. Patients with advanced stage III uterine cancer had slightly increased mRNA expression levels of Bcl-2 compared with patients with stage I cancer, although the difference was not significant. ABT-737 and radiation administration induced a synergistic cytotoxic effect based on the MTT assay and flow cytometry results, where an increase in apoptosis was observed. The apoptotic percentages were significantly increased in the cells treated with a combination of ABT-737 and irradiation. Loss of mitochondrial membrane potential and gain of reactive oxygen species (ROS) were detected by flow cytometry in CaSki and SiHa cells treated with ABT-737 and radiation. Additionally, the protein expression levels of the cleaved forms of poly ADP ribose polymerase and caspase-7 were increased following the combined treatment. In conclusion, ABT-737 and irradiation may induce apoptosis via loss of mitochondrial membrane potential and a ROS-dependent apoptotic pathway in CaSki and SiHa cells. The present study indicates that ABT-737 may be a potential irradiation adjuvant when treating cervical cancer.

12.
Int J Oncol ; 55(1): 21-34, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180559

RESUMO

Emerging studies have indicated that leucine­rich repeat kinase 2 (LRRK2) is associated with thyroid cancer (TC). The present study investigated the effect of LRRK2 on the cell cycle and apoptosis in TC, and examined the underlying mechanisms in vitro. To screen TC­associated differentially expressed genes, gene expression microarray analysis was conducted. Retrieval of pathways associated with TC from the Kyoto Encyclopedia of Genes and Genomes database indicated that the c­Jun N­terminal kinase (JNK) signaling pathway serves an essential role in TC. SW579, IHH­4, TFC­133, TPC­1 and Nthy­ori3­1 cell lines were used to screen cell lines with the highest and lowest LRRK2 expression for subsequent experiments. The two selected cell lines were transfected with pcDNA­LRRK2, or small interfering RNA against LRRK2 or SP600125 (a JNK inhibitor). Subsequently, flow cytometry, terminal deoxynucleotidyl transferase­mediated dUTP­biotin nick end labeling, a 5­ethynyl­2'­deoxyuridine assay and a scratch test was conducted to detect the cell cycle distribution, apoptosis, proliferation and migration, respectively, in each group. The LRRK2 gene was determined to be elevated in TC based on the microarray data of the GSE3678 dataset. The SW579 cell line was identified to exhibit the highest LRRK2 expression, while IHH­4 cells exhibited the lowest LRRK2 expression. LRRK2 silencing, through inhibiting the activation of the JNK signaling pathway, increased the expression levels of genes and proteins associated with cell cycle arrest and apoptosis in TC cells, promoted cell cycle arrest and apoptosis, and inhibited cell migration and proliferation in TC cells, indicating that LRRK2 repression could exert beneficial effects through the JNK signaling pathway on TC cells. These observations demonstrate that LRRK2 silencing promotes TC cell growth inhibition, and facilitates apoptosis and cell cycle arrest. The JNK signaling pathway may serve a crucial role in mediating the anti­carcinogenic activities of downregulated LRRK2 in TC.


Assuntos
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/biossíntese , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Sistema de Sinalização das MAP Quinases , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/genética , Antracenos/farmacologia , Apoptose/fisiologia , Pontos de Checagem do Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Regulação para Baixo , Ativação Enzimática , Humanos , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/metabolismo , Neoplasias da Glândula Tireoide/patologia , Transfecção
13.
Environ Pollut ; 249: 676-685, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30933765

RESUMO

Economic development puts pressure on environment through air, water and land degradation, which in turn brings real costs to the economy. Actual economy growth should therefore consider the environmental degradation cost resulted from economic activities. Pearl River Delta (PRD) region as a typical delta area with rapid development in China, is with great significance to understand the loses resulted from environmental pollution. This study conducts an environmental economic accounting within the PRD region from 2011 to 2015 using the environmental degradation cost accounting approach. We identified and calculated the economic, agricultural, industrial and social losses resulting from air, water and waste pollution with different valuation methods, which includes shadow price, replacement costs, market value method, etc. The results showed the total environmental degradation cost ranged from 18.1 to 19.8 billion US$ and the environmental degradation index declined slightly over the years, with significant differences among cities. It implied that the environmental condition of PRD region has been continuously improved over the years, but the capacity of environment control between cities had large differences. Cities in PRD region should therefore take measures tailored to their current situation to optimize their resource endowment and industrial structure, to overcome the conflicts between economic development and environmental protection. For cities with relatively high degradation cost, it is urgent to accelerate the efforts in improving the quality of the environment and ecosystem. For cities with lower degradation cost, it is important to take actions to keep on a sustainable and ecological efficient developing path. MAIN FINDINGS: The total environmental degradation cost of the PRD region is firstly calculated with insights on environmental management.


Assuntos
Conservação dos Recursos Naturais/métodos , Desenvolvimento Econômico , Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Rios/química , Agricultura , China , Cidades , Conservação dos Recursos Naturais/economia , Ecossistema , Monitoramento Ambiental/economia , Poluição Ambiental/economia , Indústrias
14.
Medicine (Baltimore) ; 98(1): e13741, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608386

RESUMO

Mantle cell lymphoma (MCL) is an invasive B-cell lymphoma with significant individual differences. Currently, MCL international prognostic index (MIPI) score and tumor cell proliferation index Ki-67 have been proved to be the most important prognostic factors. But the prognostic effect of these factors in Asian population is uncertain. This study aimed to analyze the disease characteristics and prognostic factors of Chinese MCL patients.A total of 83 cases of newly-diagnosed MCL patients diagnosed by the Department of Pathology of our hospital between January 1, 2011, and May 31, 2016, were enrolled. The disease characteristics, treatment effects, and outcomes of the patients were collected and analyzed.According to our analysis, MCL cases accounted for 6.2% of non-Hodgkin lymphoma (NHL) cases and mainly occurred in elderly males. But the proportion of patients at stage IV by Ann Arbor staging system and high-risk group by simplified-MIPI (s-MIPI) were significantly lower than that among European patients. Immunochemotherapy containing rituximab was significantly more effective than chemotherapy (overall response rate, [ORR]: 88.5% vs 65.2%, P = .021) and significantly prolonged patient survival (progression free survival [PFS]: 45.5 m vs 16.2 m, P = .001; overall survival [OS]: 58.3 m vs 22.8 m, P = .001). The multivariate analysis showed that the B symptoms, s-MIPI and administration of immunochemotherapy were independent prognostic factors that affected PFS and OS of the patients. s-MIPI and B symptom make up s-MIPI-B stratification method, by which patients in low-risk group of s-MIPI without B symptom were classified as low-risk, patients in high-risk group of s-MIPI and patients in low-risk group of s-MIPI with B symptom as high-risk, the rest as middle-risk. 3-year PFS of the 3 groups were 74.9%, 43.4% and 16.1%, respectively (P = .001). 3-year OS were 84.4%, 62.2%, 27.6% (P <.001).Chinese MCL was male predominance. We have a minor proportion of late-stage and high-risk patients compared to European patients. Immunochemotherapy was proved to significantly improve the prognosis of MCL patients. B symptoms, s-MIPI, and administration of rituximab independently influenced the outcome. s-MIPI-B prognostic stratification method may better predict the prognosis of Asian MCL patients. Still, further confirmation in larger populations is needed.


Assuntos
Linfoma de Célula do Manto/diagnóstico , Medição de Risco/métodos , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Criança , China , Feminino , Humanos , Antígeno Ki-67/análise , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto Jovem
15.
J Cell Biochem ; 120(3): 4582-4598, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30320918

RESUMO

Advanced glycation end products (AGEs) play a causative role in the complications involved with diabetes mellitus (DM). Nowadays, DM with hypothyroidism (DM-hypothyroidism) is indicative of an ascended tendency in the combined morbidity. In this study, we examine the role of the receptor (RAGE) played for AGEs in thyroid hormone (TH) secretion via the silent information regulator 1 (SIRT1)/nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) pathway. Blood samples were collected from patients with type 2 DM (T2DM)-hypothyroidism and from patients with T2DM, followed by detection of serum AGEs level. The underlying regulatory mechanisms of RAGE were analyzed in association with the treatment of high glucose, siRNA against RAGE, AGE, SIRT1, or Nrf2 vector in normal immortalized thyroid Nthy-ori 3-1 cells. Serum of patients with T2DM-hypothyroidism indicated promoted levels of AGEs vs those with just T2DM. Both AGEs and high glucose triggered cellular damage, increased oxidative stress, as well as displayed a decreased survival rate along with TH secretion in the Nthy-ori 3-1 cells. Moreover, AGEs and high glucose also led to RAGE upregulation, both SIRT1 and NRF2 downregulation, and the decreased expression of TH secretion-related proteins in Nthy-ori 3-1 cells. Notably, these alternations induced by the AGEs can be reserved by silencing RAGE or upregulating either SIRT1 or Nrf2, indicating a mechanism of regulating TH secretion through the SIRT1/Nrf2 pathway. Collectively, our data proposed that AGEs and high glucose exerted a potent effect on cellular damage and TH deficiency in Nthy-ori 3-1 cells through the RAGE upregulation as well as SIRT1/Nrf2 pathway inactivation. This mechanism may underlie the occurrence of DM-hypothyroidism.


Assuntos
Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Hipotireoidismo/metabolismo , Fator 2 Relacionado a NF-E2/biossíntese , Transdução de Sinais , Sirtuína 1/biossíntese , Hormônios Tireóideos/metabolismo , Adulto , Idoso , Linhagem Celular , Complicações do Diabetes/patologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Hipotireoidismo/patologia , Masculino , Pessoa de Meia-Idade
16.
J Cell Biochem ; 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30324763

RESUMO

Despite the administration of exogenous insulin and other medications used to control many aspects of diabetes mellitus (DM), increased oxidative stress has been increasingly acknowledged in DM development and complications. Therefore, this study aims to investigate the role of advanced glycation end-products (AGEs) in oxidative stress (OS) of thyroid cells in patients with DM. Patients with DM with or without thyroid dysfunction (TD) were enrolled. Thyroid toxic damage was induced by adding AGE-modified bovine serum albumin (AGE-BSA) to normal human thyroid follicular epithelial cells. The cell viability, cell cycle, and cell apoptosis, as well as the content of reactive oxygen species (ROS), catalase (CAT), and malondialdehyde (MDA) in cells were measured. Thyroid hormones, T3, T4, FT3, and FT4 levels were measured by enzyme-linked immunosorbent assay. Receptor for advanced glycation end products (RAGE), sirtuin1 ( Sirt1), and NF-E2-related factor 2 ( Nrf2) expressions were detected, and the mitochondrial membrane potential was measured. We found increased AGEs in the serum of DM patients with TD. By increasing AGE-BSA concentration, cell viability; the thyroid hormones T3, T4, FT3, and FT4 levels; and mitochondrial membrane potential all significantly decreased. However, the increase in AGE-BSA concentration led to an increase in cell apoptosis, RAGE, and nuclear factor-κB expressions but produced the opposite effect on Sirt1, Nrf2, and heme oxygenase-1 expressions, as well as a decrease in antioxidant response element protein levels. The AGE-BSA increased ROS and MDA levels and reduced CAT level in normal human thyroid follicular epithelial cells on a dose independence basis. Our results demonstrated that AGEs-mediated direct increase of RAGE produced OS in thyroid cells of DM by inactivating the Sirt1/Nrf2 axis.

17.
Curr Med Sci ; 38(5): 925-931, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30341531

RESUMO

Klippel-Trénaunay syndrome (KTS) is a rare angio-osteo-hypertrophic syndrome characterized by vascular malformations, soft tissue and/or bone hypertrophy, and varicose veins. For the purpose of describing the imaging findings and elucidating the role of medical imaging in the diagnosis and assessment of patient with KTS, we have reviewed the imaging data of 14 KTS patients. The imaging features on different imaging modalities were analyzed. Unilateral lower limb involvement was evident in 71% of cases (n=10) and bilateral but asymmetric lower limb involvement in the remaining 29% of cases (n=4). The most commonly depicted imaging features were varicosities in 93% (n=13), muscle hypertrophy in 79% (n=11) and venous anomalies in 64% (n=9). Other less common imaging findings included lymphedema in 29% (n=4), arterial malformations 29% (n=4), soft tissue hemangiomas 21% (n=3), pelvic and thigh phleboliths 21% (n=3), venous aneurysms 21% (n=3), bone abnormalities 14% (n=2) and lymphadenopathy 14% (n=2). A severe unilateral lower limb deformity resulting in contractures and muscle atrophy of the whole limb was depicted in 1 case. The pathognomonic marginal vein of Servelle was identified in 2 cases. AV shunt was highly suspected in 4 cases and was confirmed by DSA in 1 case, making Klippel-Trénaunay-Weber syndrome a more apt diagnosis. Associated ipsilateral duplicated renal artery was found in 1 case. We have concluded that medical imaging is the cornerstone in the diagnosis and assessment of severity and complications, follow-up and differentiation of KTS from other similar conditions. Different imaging modalities play complementary roles in the evaluation of KTS patients.


Assuntos
Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagem , Radiografia , Varizes/diagnóstico por imagem , Malformações Vasculares/diagnóstico por imagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Síndrome de Klippel-Trenaunay-Weber/fisiopatologia , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Varizes/diagnóstico , Varizes/fisiopatologia , Malformações Vasculares/diagnóstico , Malformações Vasculares/fisiopatologia , Adulto Jovem
18.
Int J Med Sci ; 15(12): 1312-1319, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30275757

RESUMO

Up to date, no study explores the relationship of single nucleotide polymorphisms (SNPs) of long non-coding RNAs HOTAIR (lncRNAs HOTAIR) with cancer recurrence and patient survival in uterine cervical cancer for Taiwanese women. We therefore designed this study to investigate the clinical roles of lncRNAs HOTAIR SNPs in cervical cancer. One hundred and sixteen patients with cervical invasive cancer and 96 patients with preinvasive lesions as well as 318 control women were consecutively recruited. LncRNAs HOTAIR SNPs rs920778, rs12427129, rs4759314 and rs1899663 were analyzed and their genotypic frequencies were examined by real-time polymerase chain reaction. The results indicated that there were no genotypic differences between patients with cervical neoplasia and normal controls as well as among patients with invasive and invasive cancer, and normal controls. However, genotype GG in lncRNAs HOTAIR SNP rs920778 was demonstrated to be a predictor for poorer cancer recurrence probability [p=0.001, hazard ratio (HR): 7.25, 95% CI: 2.19-23.96]. Furthermore, cervical cancer patients with genotype GG in lncRNAs HOTAIR rs920778 had worse overall survival (p =0.002, HR: 7.22, 95% CI: 2.09-24.92). No significant associations exhibited between lncRNAs HOTAIR SNP rs920778 and clinicopathological parameters. In conclusion, this studied lncRNAs HOTAIR SNPs are not associated with cervical carcinongensis. However, lncRNAs HOTAIR SNP rs920778 may be regarded as an independent predictor of cancer recurrence probability and overall survival in cervical cancer patients.


Assuntos
Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Feminino , Predisposição Genética para Doença , Humanos , Prognóstico , Análise de Sobrevida , Taiwan
19.
Environ Toxicol ; 33(12): 1237-1244, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30187994

RESUMO

To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Chalconas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Chalconas/administração & dosagem , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Neoplasias Hepáticas/patologia , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Sorafenibe/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Mol Cells ; 41(9): 853-867, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30165731

RESUMO

As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the Wnt/ß-catenin signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, Wnt/ß-catenin signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated Wnt/ß-catenin signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway. Besides, si-ß-catenin was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the Wnt/ß-catenin signaling pathway in human PTC.


Assuntos
Apoptose/genética , Transição Epitelial-Mesenquimal/genética , Sindecana-4/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Via de Sinalização Wnt/genética , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Inativação Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Sindecana-4/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
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