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1.
Chin J Integr Med ; 30(6): 543-550, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38532151

RESUMO

OBJECTIVE: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it. METHODS: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex. RESULTS: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01). CONCLUSIONS: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Fator 4 Semelhante a Kruppel , MicroRNAs , Neovascularização Fisiológica , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica/genética , Masculino , Isquemia Encefálica/terapia , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Camundongos , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Camundongos Endogâmicos C57BL , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/genética , Microvasos/patologia , Modelos Animais de Doenças , Angiogênese
2.
Lasers Med Sci ; 38(1): 223, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37758965

RESUMO

The choice between radiotherapy (RT) and CO2 laser surgery (CO2-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in order to identify prospective trials comparing patients who had undergone CO2-LS or RT to treat early glottic cancer. Eleven studies involving 1053 patients were included. In the selected literature, the parameter setting of CO2 laser equipment can be summarized as wavelength 10.6 µm, superpulsed mode, continuous setting, power tailored on target structures (1-3 W for subtle resections and 4-15 W for cutting a larger tumor), and approximately 2080-3900 W/cm2 of laser energy. Using RevMan 5.3, we estimated pooled odds ratios (ORs) for dichotomous variables and pooled mean differences (MDs) for continuous variables, along with associated 95% confidence intervals (CIs). The heterogeneity in the treatment variables was measured using Higgins' inconsistency test and expressed as I2 values. The continuous variables were then depicted as histograms developed using PlotDigitizer 2.6.8. Compared to patients treated with CO2-LS, those treated with RT had better jitter (MD 1.27%, 95% CI 1.21 ~ 1.32, P < 0.001), and high scores on the "Grade (MD 6.54, 95% CI 5.31 ~ 7.76, P < 0.001), Breathiness (MD 9.08, 95% CI 4.02 ~ 14.13, P < 0.001), Asthenia (MD 2.13, 95% CI 0.29 ~ 3.98, P = 0.02), and Strain (MD 3.32, 95% CI 0.57 ~ 6.07, P = 0.02)" scale. Patients treated with CO2-LS had worse local control rates (OR 3.14, 95% CI 1.52 ~ 6.48, P = 0.002) while lower incidence of second primary tumor (OR 0.30, 95% CI 0.15 ~ 0.61, P < 0.001). It is hoped that retrospective analysis can provide suggestions for early glottis patients to choose personalized treatment.


Assuntos
Neoplasias Laríngeas , Terapia a Laser , Neoplasias da Língua , Humanos , Dióxido de Carbono , Resultado do Tratamento , Estudos Retrospectivos , Microcirurgia , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Estudos Prospectivos , Terapia a Laser/efeitos adversos , Glote/cirurgia , Glote/patologia , Neoplasias da Língua/patologia
3.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6434-6441, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38212001

RESUMO

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1ß(IL-1ß) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1ß and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1ß and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Wolfiporia , Ratos , Masculino , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Ratos Sprague-Dawley , Caspase 3/metabolismo , Interleucina-18 , Transdução de Sinais , Infarto do Miocárdio/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Creatina Quinase Forma MB , Apoptose , Polissacarídeos/farmacologia , Superóxido Dismutase/metabolismo
4.
BMC Neurosci ; 23(1): 56, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171542

RESUMO

BACKGROUND: Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed. RESULTS: A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM-receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA-miRNA-mRNA target pairs were confirmed in this lncRNA‒miRNA‒mRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs. CONCLUSIONS: We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.


Assuntos
MicroRNAs , RNA Longo não Codificante , Envelhecimento , Animais , Redes Reguladoras de Genes , Hipocampo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Ratos , Reprodutibilidade dos Testes , Proteína Supressora de Tumor p53/genética , Tirosina
5.
World J Gastrointest Oncol ; 13(9): 1099-1108, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34616515

RESUMO

Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process.

6.
J Neurosci ; 39(46): 9107-9118, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31597725

RESUMO

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.


Assuntos
Axônios/metabolismo , Gânglios Espinais/metabolismo , Regeneração Nervosa , Nervo Óptico/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Telomerase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Feminino , Camundongos Endogâmicos C57BL
7.
Plant Cell ; 31(12): 2947-2972, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31628167

RESUMO

Flowers are essential but vulnerable plant organs, exposed to pollinators and florivores; however, flower chemical defenses are rarely investigated. We show here that two clustered terpene synthase and cytochrome P450 encoding genes (TPS11 and CYP706A3) on chromosome 5 of Arabidopsis (Arabidopsis thaliana) are tightly coexpressed in floral tissues, upon anthesis and during floral bud development. TPS11 was previously reported to generate a blend of sesquiterpenes. By heterologous coexpression of TPS11 and CYP706A3 in yeast (Saccharomyces cerevisiae) and Nicotiana benthamiana, we demonstrate that CYP706A3 is active on TPS11 products and also further oxidizes its own primary oxidation products. Analysis of headspace and soluble metabolites in cyp706a3 and 35S:CYP706A3 mutants indicate that CYP706A3-mediated metabolism largely suppresses sesquiterpene and most monoterpene emissions from opening flowers, and generates terpene oxides that are retained in floral tissues. In flower buds, the combined expression of TPS11 and CYP706A3 also suppresses volatile emissions and generates soluble sesquiterpene oxides. Florivory assays with the Brassicaceae specialist Plutella xylostella demonstrate that insect larvae avoid feeding on buds expressing CYP706A3 and accumulating terpene oxides. Composition of the floral microbiome appears also to be modulated by CYP706A3 expression. TPS11 and CYP706A3 simultaneously evolved within Brassicaceae and form the most versatile functional gene cluster described in higher plants so far.plantcell;31/12/2947/FX1F1fx1.


Assuntos
Alquil e Aril Transferases/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Flores/metabolismo , Terpenos/antagonistas & inibidores , Alquil e Aril Transferases/genética , Animais , Arabidopsis/enzimologia , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Flores/genética , Flores/microbiologia , Expressão Gênica , Larva , Microbiota , Modelos Moleculares , Simulação de Acoplamento Molecular , Monoterpenos/metabolismo , Mariposas , Família Multigênica , Filogenia , Sesquiterpenos/metabolismo , Terpenos/química , Terpenos/metabolismo , Nicotiana/metabolismo , Leveduras/metabolismo
8.
J Cell Biochem ; 120(11): 18600-18607, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31338882

RESUMO

Lung cancer (especially, non-small cell lung cancer [NSCLC]) is one of the most malignant cancers in the world. Hinesol is the major component of the essential oil of Atractylodes lancea (Thunb.) DC and possesses the most promising anticancer function. However, the effects and molecular mechanism of hinesol on antiproliferation in NSCLC cells has not been well understood. In this study, we found that hinesol effectively inhibited the A549 and NCI-H1299 cells in a dose- and time-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. In addition, hinesol induced cell cycle arrest at G0/G1 phase and apoptosis assessed by flow cytometry in A549 cells. Furthermore, Western blot analysis showed that hinesol decreased phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, IκBα, and p65 inhibited the expressions of Bcl-2, cyclin D1 and upregulated the expression of Bax. Based on these results, hinesol might be a potential drug candidate of anti-NSCLC for therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Atractylodes/química , Proliferação de Células/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Sesquiterpenos/farmacologia , Compostos de Espiro/farmacologia , Células A549 , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estrutura Molecular , Extratos Vegetais/farmacologia , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Sesquiterpenos/química , Compostos de Espiro/química , Fatores de Tempo
9.
Clin Exp Pharmacol Physiol ; 46(1): 75-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30221384

RESUMO

Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.


Assuntos
Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Receptores ErbB/antagonistas & inibidores , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Tirfostinas/farmacologia , Animais , Progressão da Doença , Feminino , Inflamação/patologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/patologia , Tirfostinas/uso terapêutico
10.
Mediators Inflamm ; 2018: 4934592, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057486

RESUMO

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Cumarínicos/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Transporte Ativo do Núcleo Celular , Lesão Pulmonar Aguda/induzido quimicamente , Adjuvantes Imunológicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar , Ensaio de Imunoadsorção Enzimática , Lesão Pulmonar/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/metabolismo
11.
Ann Thorac Surg ; 106(4): 1251-1257, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29738756

RESUMO

BACKGROUND: In this study, we investigated the clinical significance of endobronchial ultrasound elastography for differentiating malignant and benign intrathoracic lymph nodes. METHODS: A meta-analysis was performed to evaluate the sensitivity and specificity of endobronchial ultrasound elastography in diagnosing intrathoracic lymph nodes. Publications before October 1, 2017, were included for analysis. Sensitivity, specificity, and other variables were pooled using the bivariate mixed-effects regression model. RESULTS: Seven studies met the inclusion criteria and were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio was 0.93 (95% confidence interval [CI], 0.85 to 0.97), 0.85 (95% CI, 0.78 to 0.90), 6.3 (95% CI, 4.2 to 9.2), 0.08 (95% CI, 0.04 to 0.18), and 74 (95% CI, 33 to 168), respectively. The summary receiver operating characteristic curve was 0.93 (95% CI, 0.91 to 0.95). CONCLUSIONS: The results revealed endobronchial ultrasound elastography is a new technique with high sensitivity and specificity. It has a fine performance in diagnosing intrathoracic lymph nodes.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Endossonografia/métodos , Linfonodos/diagnóstico por imagem , Cavidade Torácica/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Linfonodos/patologia , Masculino , Imagem Multimodal/métodos , Curva ROC , Sensibilidade e Especificidade , Cavidade Torácica/patologia
12.
Proc Natl Acad Sci U S A ; 115(23): E5410-E5418, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29784821

RESUMO

Gossypol and related sesquiterpene aldehydes in cotton function as defense compounds but are antinutritional in cottonseed products. By transcriptome comparison and coexpression analyses, we identified 146 candidates linked to gossypol biosynthesis. Analysis of metabolites accumulated in plants subjected to virus-induced gene silencing (VIGS) led to the identification of four enzymes and their supposed substrates. In vitro enzymatic assay and reconstitution in tobacco leaves elucidated a series of oxidative reactions of the gossypol biosynthesis pathway. The four functionally characterized enzymes, together with (+)-δ-cadinene synthase and the P450 involved in 7-hydroxy-(+)-δ-cadinene formation, convert farnesyl diphosphate (FPP) to hemigossypol, with two gaps left that each involves aromatization. Of six intermediates identified from the VIGS-treated leaves, 8-hydroxy-7-keto-δ-cadinene exerted a deleterious effect in dampening plant disease resistance if accumulated. Notably, CYP71BE79, the enzyme responsible for converting this phytotoxic intermediate, exhibited the highest catalytic activity among the five enzymes of the pathway assayed. In addition, despite their dispersed distribution in the cotton genome, all of the enzyme genes identified show a tight correlation of expression. Our data suggest that the enzymatic steps in the gossypol pathway are highly coordinated to ensure efficient substrate conversion.


Assuntos
Gossipol/biossíntese , Gossipol/metabolismo , Vias Biossintéticas , Gossypium/metabolismo , Isomerases/biossíntese , Isomerases/metabolismo , Folhas de Planta/metabolismo , Sesquiterpenos Policíclicos , Sesquiterpenos/metabolismo , Transcriptoma/efeitos dos fármacos
13.
J Ophthalmol ; 2018: 2827491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30595911

RESUMO

PURPOSE: To evaluate the efficacy, feasibility, and safety of the navigation-guided endoscopy combined with deep lateral orbitotomy for removal of small tumors at the lateral orbital apex. DESIGN: A retrospective, noncomparative case series. METHODS: Retrospective analysis of ten patients (10 eyes) with small tumors at the lateral orbital apex comprised navigation-guided endoscopy combined with deep lateral orbitotomy at the Eye Hospital of Wenzhou Medical University from November 2015 to November 2017. In each case, the indication of surgery was existing or imminent visual impairment due to the tumor. The removal was believed to be complete if the mass was removed intactly during the surgery. The tumor character was confirmed by pathological examination after surgery. Patients were followed up to 3 months after surgery. Best corrected visual acuity before and after surgery was compared. RESULTS: All tumors were completely removed by the navigation-guided endoscopic approach. The mean preoperative best corrected visual acuity was 6/15 (95% confidence interval (95% CI) 6/40-6/8.5), and the mean postoperative best corrected visual acuity was 6/10 (95% CI 6/15-6/7.5). 5 of 7 (71%) patients with vision loss gained visual improvement in different degrees after surgery, and the rest of the patients had preoperative best corrected visual acuity. Visual field of all patients also improved. 8 cavernous hemangiomas and 2 schwannomas were confirmed postoperatively by pathology. 4 patients accompanied with limitation of eye abduction, which recovered spontaneously in an average of 4 weeks. No other serious complications occurred. CONCLUSIONS: Navigation-guided endoscopy combined with deep lateral orbitotomy seems to be a feasible, efficient, and safe approach for removing small tumors at the lateral orbital apex. This trial is registered with ChiCTR1800019244.

14.
Biomed Res Int ; 2017: 4702067, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28428961

RESUMO

Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which may play a key role in the development of sepsis, and insulin has been reported to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly allocated into five groups: control group, cecal ligation and puncture (CLP) group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h after surgery. Histological and cytokine analyses, intestinal permeability tests, and western blots of intestinal epithelial tight junction component proteins and UCP2 were performed. Compared with CLP group, the CLP + GIK group had milder histological damage, lower levels of cytokines in the serum and ileum tissue samples, and lower UCP2 expression, whereas the CLP + GK group had no such effects. Moreover, the CLP + GIK group exhibited decreased epithelial permeability of the ileum and increased expression of zonula occludens-1, occludin, and claudin-1 in the ileum. The findings demonstrated that the UCP2 and NLR family-pyrin domain-containing 3/caspase 1/interleukin 1ß signaling pathway may be involved in intestinal barrier injury and that GIK treatment decreased intestinal barrier permeability. Thus, GIK may be a useful treatment for intestinal barrier injury during sepsis.


Assuntos
Coinfecção/tratamento farmacológico , Enteropatias/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Sepse/tratamento farmacológico , Proteína Desacopladora 2/genética , Animais , Caspase 1/genética , Coinfecção/microbiologia , Coinfecção/patologia , Modelos Animais de Doenças , Glucose/administração & dosagem , Humanos , Inflamassomos/genética , Insulina/administração & dosagem , Interleucina-1beta/genética , Enteropatias/microbiologia , Enteropatias/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Potássio/administração & dosagem , Domínio Pirina/genética , Ratos , Sepse/microbiologia , Sepse/patologia
15.
ACS Appl Mater Interfaces ; 9(5): 4475-4484, 2017 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-28103014

RESUMO

A dual redox and biorelevant triggered supramolecular system is developed through noncovalent supramolecular inclusion interactions between the ferrocene (Fc) modified on camptothecin (CPT) and ß-cyclodextrin (ß-CD) at the end of methoxy polyethylene glycol (mPEG). With these two segments, a stable noncovalent supramolecular structure, i.e., mPEG-ß-CD/Fc-CPT, can be formed, and then self-assembled into micellar structures in water. Interestingly, these supramolecular micelles showed uniform sphere structure, high and constant drug loading content, hyper-fast redox-responsive drug release, and exhibited equal cellular proliferation inhibition toward A549 cancer cells. The cytotoxicity evaluation of mPEG-ß-CD also indicated good biocompatibility. In vivo results revealed the mPEG-ß-CD/Fc-CPT nanoparticles had higher in vivo efficacy without side effects. It is anticipated this supramolecular complex may serve as a new kind of promising alternative for drug delivery systems.

16.
Sci Rep ; 5: 14139, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26420475

RESUMO

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD)2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11-20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum, conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.


Assuntos
Evolução Biológica , Fibra de Algodão , Genoma de Planta , Genômica , Gossypium/genética , Gossypium/metabolismo , Metabolômica , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Cromossomos de Plantas , Análise por Conglomerados , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Estudos de Associação Genética , Genômica/métodos , Metabolômica/métodos , Anotação de Sequência Molecular , Fenótipo , Filogenia , Poliploidia , Característica Quantitativa Herdável , Sesquiterpenos/metabolismo , Translocação Genética , Fitoalexinas
17.
Gene ; 550(1): 27-32, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25106857

RESUMO

To investigate the role of TLR3/PI3K signals in the occurrence and development of cervical cancer disease, TLR3-siRNA was used to block key signaling pathways involved in cervical cancer metastasis that are pivotal to metastatic tumor cells but not to normal cells under ordinary physiologic conditions. Results show that tumor U14 cell growth, migration and invasion in TLR3-siRNA treatment group were significantly decreased. Through LY294002 suppressing targeted gene, the LY294002 treatment specifically and significantly knocked down the expressions of tumor TLR3 and PI3K proteins in cervical cancer mice. Furthermore, expressions of tumor Survivin and FasL proteins were markedly suppressed, whereas expressions of Fas protein were upregulated in LY294002 treatment group mice. LY294002 treatment suppressed tumor growth and increased the thymus and spleen indeces and survival days of cervical cancer mice. This study demonstrates that TLR3-siRNA and LY294002 treatments can markedly suppress cervical cancer cell invasion and tumor growth and increase survival life by silencing targeted genes.


Assuntos
Proteína Ligante Fas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Repressoras/metabolismo , Receptor 3 Toll-Like/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Proteína Ligante Fas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/genética , Camundongos , Camundongos Endogâmicos BALB C , Morfolinas/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Interferência de RNA , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Baço/efeitos dos fármacos , Baço/patologia , Survivina , Timo/efeitos dos fármacos , Timo/patologia , Receptor 3 Toll-Like/genética , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/prevenção & controle , Receptor fas
18.
Zhonghua Fu Chan Ke Za Zhi ; 48(11): 828-32, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24444559

RESUMO

OBJECTIVE: To explore the value of transthoracic echocardiography(TTE) combined with partial pressure of end-tidal CO2 (P ETCO2) monitoring in preventing venous air embolism(VAE) during hysteroscopy operation. METHODS: From August 2010 to August 2012, 300 cases undergoing hysteroscopic surgery under general anaesthesia were enrolled in this study. With the echocardiography combined with P ETCO2 monitoring during hysteroscopic surgery, the time of VAE appearing in the right atrium , the extent of air embolism(grade 0-4), the changes of P ETCO2, peripheral oxygen saturation (SpO2), blood pressure (Bp), the amount of fluid intravasation and the blood loss were recorded in detail . Take the 24 cases that the grades of VAE in grade 3 or above and a decrease in P ETCO2 ≥ 5 mm Hg (1 mm Hg = 0.133 kPa) as intervention group. Stop operation immediately, the left side and raise your right shoulder, oxygen inhalation and dexamethasone 10 mg intravenous drip were given to the intervention group; the control group (5 cases in grade 3 or above and a decrease in P ETCO2<5 mm Hg) only stop operation immediately, observation patient's condition closely. RESULTS: (1) The occurrence of VAE: air embolism occurred in 34 patients among all 300 patients, all of 34 patients had evidence of gas embolism in the inferior vena cava, right atrium(RA) and right ventricle chamber, and 29 patients had evidence of continuous groups of gas emboli. There were 32 cases with the decrease in P ETCO2 > 2 mm Hg, 14 cases with SpO2 less than 95%, and 4 cases with a drop in Bp ≥ 20%. (2) The change of the decrease of P ETCO2 and the grades of VAE: the decrease of P ETCO2 and the grades of VAE were positively correlated (r = 0.601, P < 0.01), continuous groups of gas emboli signal in RA, when the drop of P ETCO2 ≥ 5 mm Hg, 8 of the 34 cases whose drop of P ETCO2 ≥ 10 mm Hg, 7 cases in grades 4. The decrease of P ETCO2 [(7.5 ± 2.4) mm Hg versus (11.1 ± 4.1) mm Hg], the amount of fluid intravasation[(688 ± 150) ml versus (925 ± 268) ml] and the blood loss[(71 ± 36) ml versus (127 ± 56) ml] all had statistical difference in grade 3 and 4 (P < 0.05) . The sensitivity of P ETCO2 was better than SpO2 and Bp in detecting of VAE. (3) The cases of P ETCO2 continue to decline and recovery time between the two groups:2 cases' P ETCO2 continued to decline in the intervention group, but 4 cases in the control group. The recovery time of the two groups was (4.8 ± 1.6) and (8.3 ± 1.9) min, respectively, which reached statistical difference between (P < 0.05). CONCLUSIONS: TTE combined with P ETCO2 monitoring can effectively predict the occurrence of air embolism in hysteroscopic surgery; Continuous groups of gas emboli signal in RA accompanied by a decrease in P ETCO2 ≥ 5 mm Hg indicates that the occurrence of air embolism; the more the amount of intravasation of distension fluid and the blood loss, the more the air into the body. Timely intervention can effectively prevent the development of air embolism when the VAE in grade 3 or above accompanied by a decrease in P ETCO2 ≥ 5 mm Hg.


Assuntos
Capnografia , Ecocardiografia , Embolia Aérea/prevenção & controle , Histeroscopia/efeitos adversos , Doenças Uterinas/cirurgia , Adulto , Pressão Sanguínea , Dióxido de Carbono , Embolia Aérea/diagnóstico , Feminino , Humanos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/prevenção & controle , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Oximetria , Função Ventricular Direita , Adulto Jovem
19.
Zhonghua Fu Chan Ke Za Zhi ; 47(11): 813-7, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23302120

RESUMO

OBJECTIVE: To investigate the clinical value of non-invasive prenatal diagnosis using cell free fetal DNA (cff-DNA) in maternal blood. METHODS: From Sep. 2010 to Mar. 2012, 103 pregnant women who came to Henan Province People's Hospital in the first trimester for prenatal diagnosis of sex-linked inherited diseases were included in the first trimester group. From Oct. 2010 to Jan. 2012, 205 pregnant women undergoing amniotic fluid sampling for fetal karyotype analysis in the same hospital were included in the second trimester group. Real time quantitative PCR and fluorescent PCR were used to detect sex determining region of Y chromosome gene (SRY) and amelogenin gene (AML) on cff-DNA of the first trimester group. Moreover, 12 Y chromosome STR loci analysis were performed for 33 male fetuses and their fathers. Massively Parallel Signature Sequencing (MPSS) was used for aneuploidy analysis in cff-DNA of the second trimester group. RESULTS: (1) In the first trimester group, there were 53 SRY positive and 50 SRY negative. Compared with the results of cff-DNA of chorionic villus samples, there was one SRY false positive and one false negative results, with a sensitivity of 98% and specificity of 98%. For the AML gene test, there were two PCR products of male fetuses:102 bp fragment originating from X chromosome (AML X) and 108 bp fragment from Y chromosome (AML Y); but only AML X was found in products from female fetuses. In the first trimester group, 102 bp and 108 bp fragments were detected in 52 cases, and only 102 bp fragment was found in the other cases. Compared to AML results from chorionic villus samples, there were 2 false negative results, with a sensitivity of 96% and specificity of 100%. (2) For cff-DNA with plasma SRY over 30 copy/ml, Y STR loci were analyzed on cff-DNA of 33 fetuses and their fathers. The Y STR loci less then 200 bp were successfully detected, while Y STR loci with PCR products between 200-300 bp showed low signal or could not be amplicated; and no PCR products more than 300 bp were detected from cff-DNA. Comparing the detected Y STR loci of cff-DNA to the fathers, 32 fetuses were concordant with their fathers'. Exogenous contamination was found in the rest one sample. (3) In the second trimester group, 6 fetuses with abnormal karyotype (two trisomy 21, three trisomy 18 and one 45, XO) were detected by cff-DNA and were proved by karyotype analysis. Moreover, the MPSS results of cff-DNA revealed one 45, Y and one trisomy 16 whose karyotype analysis showed normal results. And in one case, MPSS suggested less chrX or chrY, that was proved to be 47, XYY by karyotype analysis. CONCLUSIONS: (1) Cff-DNA in maternal blood can be used to determine fetal gender in early prenancy with considerable sensitivity and specificity. But the trace cff-DNA and the high maternal DNA background might have impact on the result. (2) Analysis of cff-DNA in maternal blood of the second trimester women showed that MPSS could be used for prenatal screening of trisomy 21 and trisomy 18. However, further research should be done for other chromosomes aneuploidy detection.


Assuntos
Aneuploidia , Transtornos Cromossômicos/diagnóstico , DNA/sangue , Cariotipagem , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/sangue , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Y/genética , Feminino , Humanos , Masculino , Testes para Triagem do Soro Materno , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Sensibilidade e Especificidade , Trissomia/diagnóstico
20.
Zhonghua Jie He He Hu Xi Za Zhi ; 34(12): 919-22, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22333505

RESUMO

OBJECTIVE: To explore the clinical characteristics, complications and prognosis of Peutz-Jeghers syndrome. METHODS: The clinical manifestations, imaging characteristics and pathological data of one patient with Peutz-Jeghers syndrome treated in Shaoxing People's Hospital were presented, and 3 cases of Peutz-Jeghers syndrome complicated with lung cancer reported in the literature were reviewed. The literature review was carried out by searching the Pubmed and CBMdisc database with Peutz-Jeghers syndrome and lung cancer as the key words. RESULTS: The patient treated in our hospital was a 30-year-old female. The primary manifestations were cough, sputum production and hemoptysis. Multiple gastrointestinal hamartomatous polyps were found, and associated with melanin pigmentation of the buccal mucosa, the lips, the hands and the feet. Therefore the diagnosis of Peutz-Jeghers syndrome was made. Chest CT scan showed a peripheral nodule at the right lower lobe, which was confirmed to be lung mucinous adenocarcinoma by surgery and pathology. The 3 cases reported in the literature were males aging from 22 to 43 years old. Cough, expectoration and hemoptysis were defined as the manifestations for 2 patients, and another case was found by physical check-up. They all died within a short period. Pathological study revealed adenocarcinoma of the lung in all the cases. CONCLUSION: Peutz-Jeghers syndrome complicated with lung cancer is rare and has a poor prognosis.


Assuntos
Adenocarcinoma Mucinoso/complicações , Neoplasias Pulmonares/complicações , Síndrome de Peutz-Jeghers/complicações , Adulto , Feminino , Humanos , Prognóstico
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