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1.
Environ Toxicol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747344

RESUMO

Breast cancer (BC) is a heterogeneous malignancy with a dismal prognosis. Disulfidptosis is a novel type of regulated cell death that happens in the presence of glucose deficiency and is linked to the metabolic process of glycolysis. However, the mechanism of action of disulfidptosis and glycolysis-related genes (DGRG) in BC, as well as their prognostic value in BC patients, remain unknown. After identifying the differentially expressed DGRG in normal and BC tissues, a number of machine learning algorithms were utilized to select essential prognostic genes to develop a model, including SLC7A11, CACNA1H, SDC1, CHST1, and TFF3. The expression characteristics of these genes were then examined using single-cell RNA sequencing, and BC was classified into three clusters using "ConsensusClusterPlus" based on these genes. The DGRG model's median risk score can categorize BC patients into high-risk and low-risk groups. Furthermore, we investigated variations in clinical landscape, immunoinvasion analysis, tumor immune dysfunction and rejection (TIDE), and medication sensitivity in patients in the DGRG model's high- and low-risk groups. Patients in the low-risk group performed better on immunological and chemotherapeutic therapies and had lower TIDE scores. In conclusion, the DGRG model we developed has significant clinical application potential because it can accurately predict the prognosis of BC, TME, and pharmacological treatment responses.

3.
Mar Drugs ; 21(6)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37367654

RESUMO

Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3ß signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3ß, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3ß signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.


Assuntos
Glioblastoma , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Caspase 3/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Pelados , Proliferação de Células , Transdução de Sinais , Apoptose , Glioblastoma/patologia , Linhagem Celular Tumoral
4.
Endocr Connect ; 12(2)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36524799

RESUMO

Background: Papillary thyroid carcinoma is the most common thyroid carcinoma worldwide. Papillary thyroid carcinoma metastasis to the cervical region increases the probability of local or regional recurrence and the requirement for further surgery. Contrast-enhanced ultrasound has been suggested as a possible adjunct diagnostic technique for evaluating papillary thyroid carcinoma metastatic lymph nodes in several studies. This meta-analysis aims to evaluate the diagnostic accuracy of contrast-enhanced ultrasound for cervical lymph nodes metastatic in papillary thyroid carcinoma patients. Methods: A search for studies evaluating the role of contrast-enhanced ultrasound for assessing cervical lymph nodes metastatic in papillary thyroid carcinoma patients from January 2000 to May 2022 was performed in PubMed, Embase, OVID, and Web of Science databases. The Quality Assessment of Diagnostic Accuracy Studies 2 evaluated the quality of the studies. All analyses were performed using Review Manager 5.3 and Stata 17.0. Results: A total of seven articles were finally included in this study. Perfusion type, enhancement homogeneous, hilum absent, and perfusion defect were involved in the meta-analysis as the standard of contrast-enhanced ultrasound, among which, perfusion type showed the best diagnostic performance. The pooled estimated sensitivity, specificity, positive likelihood, negative likelihood ratio, and diagnostic odds ratio of perfusion type in contrast-enhanced ultrasound for detecting lymph node metastasis were 0.95 (0.91, 0.97), 0.87 (0.69, 0.96), 7.51 (2.80, 20.14), 0.06 (0.03, 0.10), and 124.17 (42.78, 360.46), respectively. Heterogeneity was moderate. Conclusion: The perfusion type in contrast-enhanced ultrasound has good diagnostic performance for cervical lymph nodes metastasis in papillary thyroid carcinoma patients.

5.
Pharmacol Res ; 187: 106565, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36414124

RESUMO

A primary strategy employed in cancer therapy is the inhibition of topoisomerase II (Topo II), implicated in cell survival. However, side effects and adverse reactions restrict the utilization of Topo II inhibitors. Thus, investigations focus on the discovery of novel compounds that are capable of inhibiting the Topo II enzyme and feature safer toxicological profiles. Herein, we upgrade an old antibiotic chrysomycin A from Streptomyces sp. 891 as a compelling Topo II enzyme inhibitor. Our results show that chrysomycin A is a new chemical entity. Notably, chrysomycin A targets the DNA-unwinding enzyme Topo II with an efficient binding potency and a significant inhibition of intracellular enzyme levels. Intriguingly, chrysomycin A kills KRAS-mutant lung adenocarcinoma cells and is negligible cytotoxic to normal cells at the cellular level, thus indicating a capability of potential treatment. Furthermore, mechanism studies demonstrate that chrysomycin A inhibits the Topo II enzyme and stimulates the accumulation of reactive oxygen species, thereby inducing DNA damage-mediated cancer cell apoptosis. Importantly, chrysomycin A exhibits excellent control of cancer progression and excellent safety in tumor-bearing models. Our results provide a chemical scaffold for the synthesis of new types of Topo II inhibitors and reveal a novel target for chrysomycin A to meet its further application.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Inibidores da Topoisomerase II , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , DNA Topoisomerases Tipo II/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase II/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia
6.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234681

RESUMO

Chrysomycin A (Chr-A), an antibiotic from Streptomyces, is reported to have anti-tumor and anti-tuberculous activities, but its anti-glioblastoma activity and possible mechanism are not clear. Therefore, the current study was to investigate the mechanism of Chr-A against glioblastoma using U251 and U87-MG human cells. CCK8 assays, EdU-DNA synthesis assays and LDH assays were carried out to detect cell viability, proliferation and cytotoxicity of U251 and U87-MG cells, respectively. Transwell assays were performed to detect the invasion and migration abilities of glioblastoma cells. Western blot was used to validate the potential proteins. Chr-A treatment significantly inhibited the growth of glioblastoma cells and weakened the ability of cell migration and invasion by down regulating the expression of slug, MMP2 and MMP9. Furthermore, Chr-A also down regulated Akt, p-Akt, GSK-3ß, p-GSK-3ß and their downstream proteins, such as ß-catenin and c-Myc in human glioblastoma cells. In conclusion, Chr-A may inhibit the proliferation, migration and invasion of glioblastoma cells through the Akt/GSK-3ß/ß-catenin signaling pathway.


Assuntos
Glioblastoma , beta Catenina , Aminoglicosídeos , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , DNA/farmacologia , Glioblastoma/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo
7.
Anal Bioanal Chem ; 414(27): 7911-7922, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36138121

RESUMO

To investigate the diagnostic efficiency of Raman spectroscopy for the diagnosis of breast cancer, we searched PubMed, Web of Science, Cochrane Library, and Embase for articles published from the database establishment to May 20, 2022. Pooled sensitivity, specificity, diagnostic odds ratio, and area under the receiver pooled operating characteristic curve were derived for the included studies as outcome measures. The methodological quality was assessed according to the questionnaires and criteria suggested by the Diagnostic Accuracy Research Quality Assessment-2 tool. Sixteen studies were included in this meta-analysis. The pooled sensitivity and specificity of Raman spectroscopy for breast cancer diagnosis were 0.97 (95% CI, [0.92-0.99]) and 0.96 (95% CI, [0.91-0.98]). The diagnostic odds ratio was 720.89 (95% CI, [135.73-3828.88]) and the area under the curve of summary receiver operating characteristic curves was 0.99 (95% CI, [0.98-1]). Subgroup analysis revealed that all subgroup types in our analysis, including different races, sample types, diagnostic algorithms, number of spectra, instrument types, and laser wavelengths, turned out to have a sensitivity and specificity greater than 0.9. Significant heterogeneity was found between studies. Deeks' funnel plot demonstrated that publication bias was acceptable. This meta-analysis suggests that Raman spectroscopy may be an effective and accurate tool to differentiate breast cancer from normal breast tissue, which will help us diagnose and treat breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Curva ROC , Sensibilidade e Especificidade , Análise Espectral Raman/métodos
8.
Front Endocrinol (Lausanne) ; 13: 952113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966062

RESUMO

Background: Papillary thyroid cancer (PTC) is the most common thyroid tumor, and early diagnosis and treatment can effectively improve prognosis. Many controversies surround the treatment method of T1N0M0 PTC. Recently, thermal ablation (TA) has shown some benefits in the treatment of PTC patients, but the safety and efficacy of its treatment remain controversial. This article performs a meta-analysis of TA in patients with T1aN0M0 and T1bN0M0 PTC. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for retrospective or prospective studies of TA for treating patients with T1N0M0 PTC from the database establishment to May 1, 2022. Data on volume reduction rate (VRR), disease progress, and complication rate were collected. In addition, a meta-analysis was performed using the Stata 12.0 and Review Manager 5.3. Results: A total of 9 eligible studies were included. Our study demonstrated the effectiveness of VRR and disease progress. The VRR was reduced after 3 months (-75.90%; 95% CI [-118.46-33.34%]), 6 months (34.33%; 95% CI [15.01-53.65%]), 12 months (78.69%; 95% CI [71.69-85.68%]), and 24 months (89.97%; 95% CI [84.00-95.94%]). The disease progress was 1.9% (95% CI [1.1-3.0]). Safety is justified by the complication rate, which was 6.5% (95% CI [3.5-10.2]). Pain and hoarseness were the most common complications, and no life-threatening complications were reported. Egger's test demonstrated that publication bias was acceptable. Conclusions: TA is an effective and safe method for managing T1aN0M0 and T1bN0M0 papillary thyroid nodules.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Ultrassonografia de Intervenção
10.
J Clin Ultrasound ; 50(2): 224-226, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34889462

RESUMO

This case illustrates the untypical presentation of primary bladder malacoplakia. The patient was in her mid-50s have impaired immunity by the long-term hyperglycemic condition. She presented with symptoms of urinary tract infection and dysuria, and had multiple nodulars in bladder and significantly mass in urethra. Although the diagnosis of bladder malacoplakia was established on bladder biopsy, transperineal ultrasound examination can find its distinct clinical presentation.


Assuntos
Malacoplasia , Infecções Urinárias , Feminino , Humanos , Malacoplasia/diagnóstico por imagem , Masculino , Ultrassonografia , Uretra/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem
11.
Front Genet ; 13: 1104338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685904

RESUMO

Background: Circadian dysregulation is linked to the onset and progression of cancer, but current knowledge of the role of circadian rhythm-related genes (CRRGs) in breast cancer (BC) is limited and incomplete. The purpose of this study was to investigate the potential role and immune-related prognostic significance of CRRGs in BC. Methods: The Cancer Genome Atlas breast cancer (TCGA-BRCA) genetic data were combined with 1369 CRRGs to create a model of BC prognosis-related CRRGs. To validate the model's predictive power in TCGA and other external datasets, the Kaplan-Meier survival curve and receptor operation characteristic curve were plotted. The relationship between CRRGs model and gene enrichment pathways, immune cell infiltration, and differences in patient response to immune checkpoint inhibitors (ICIs) therapy was then discussed. Results: A CRRG-based eighteen-gene model was developed that accurately predicted the survival time of BC patients. Based on this model, BC patients can be classified as high or low risk. The high-risk group has negative immune cell infiltration (such as macrophages M0 and M2) and a poor therapeutic response to ICIs due to lower immune checkpoint gene expression. Furthermore, TCF7 and IFNG were found to be strongly associated with immune checkpoints in CRRGs model. Conclusion: The 18 CRRGs may be useful in assessing the prognosis of BC patients, studying immune infiltration, and developing more effective immunotherapy strategies.

12.
Environ Microbiol ; 23(11): 6981-6992, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34490968

RESUMO

Bacterial secondary metabolites are rich sources of novel drug leads. The diversity of secondary metabolite biosynthetic gene clusters (BGCs) in genome-sequenced bacteria, which will provide crucial information for the efficient discovery of novel natural products, has not been systematically investigated. Here, the distribution and genetic diversity of BGCs in 10 121 prokaryotic genomes (across 68 phyla) were obtained from their PRISM4 outputs using a custom python script. A total of 18 043 BGCs are detected from 5743 genomes with non-ribosomal peptide synthetases (25.4%) and polyketides (15.9%) as the dominant classes of BGCs. Bacterial strains harbouring the largest number of BGCs are revealed and BGC count in strains of some genera vary greatly, suggesting the necessity of individually evaluating the secondary metabolism potential. Additional analysis against 102 strains of discovered bacterial genera with abundant amounts of BGCs confirms that Kutzneria, Kibdelosporangium, Moorea, Saccharothrix, Cystobacter, Archangium, Actinosynnema, Kitasatospora, and Nocardia, may also be important sources of natural products and worthy of priority investigation. Comparative analysis of BGCs within these genera indicates the great diversity and novelty of the BGCs. This study presents an atlas of bacterial secondary metabolite BGCs that provides a lot of key information for the targeted discovery of novel natural products.


Assuntos
Vias Biossintéticas , Cianobactérias , Família Multigênica , Vias Biossintéticas/genética , Cianobactérias/genética , Metabolismo Secundário/genética
13.
Food Chem ; 341(Pt 1): 128148, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33038776

RESUMO

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.


Assuntos
Hipoglicemiantes/farmacologia , Polissacarídeos/farmacologia , Alga Marinha/química , Undaria/química , Animais , Fracionamento Químico , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Glucose/farmacocinética , Células Hep G2 , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Hipoglicemiantes/química , Insulina/farmacologia , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Micro-Ondas , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Período Pós-Prandial , Sulfatos/química
14.
J Cell Mol Med ; 24(18): 10604-10614, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32735065

RESUMO

Inflammatory cell infiltration contributes to the pathogenesis of acute respiratory distress syndrome (ARDS). Protectin DX (PDX), an endogenous lipid mediator, shows anti-inflammatory and proresolution bioactions. In vivo, the mice were intraperitoneally injected with PDX (0.1 µg/mouse) after intratracheal (1 mg/kg) or intraperitoneal (10 mg/kg) LPS administration. Flow cytometry was used to measure inflammatory cell numbers. Clodronate liposomes were used to deplete resident macrophages. RT-PCR, and ELISA was used to measure MIP-2, MCP-1, TNF-α and MMP9 levels. In vitro, sorted neutrophils, resident and recruited macrophages (1 × 106 ) were cultured with 1 µg/mL LPS and/or 100 nmol/L PDX to assess the chemokine receptor expression. PDX attenuated LPS-induced lung injury via inhibiting recruited macrophage and neutrophil recruitment through repressing resident macrophage MCP-1, MIP-2 expression and release, respectively. Finally, PDX inhibition of neutrophil infiltration and transmembrane was associated with TNF-α/MIP-2/MMP9 signalling pathway. These data suggest that PDX attenuates LPS-stimulated lung injury via reduction of the inflammatory cell recruitment mediated via resident macrophages.


Assuntos
Lesão Pulmonar Aguda/patologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Administração Intranasal , Animais , Quimiocina CCL2/biossíntese , Quimiocina CCL2/genética , Quimiocina CXCL2/biossíntese , Quimiocina CXCL2/genética , Quimiocina CXCL2/fisiologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Ácido Clodrônico/administração & dosagem , Ácido Clodrônico/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/fisiologia , Inflamação , Injeções Intraperitoneais , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/toxicidade , Lipossomos , Macrófagos/fisiologia , Metaloproteinase 9 da Matriz/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Receptores CCR2/antagonistas & inibidores , Receptores de Interleucina-8B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/fisiologia
15.
J Cell Mol Med ; 24(17): 9646-9657, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32757380

RESUMO

Acute respiratory distress syndrome (ARDS) is a fatal disease characterized by excessive infiltration of inflammatory cells. MCTR1 is an endogenously pro-resolution lipid mediator. We tested the hypothesis that MCTR1 accelerates inflammation resolution through resident M2 alveolar macrophage polarization. The mice received MCTR1 via intraperitoneal administration 3 days after LPS stimulation, and then, the bronchoalveolar lavage (BAL) fluid was collected 24 hours later to measure the neutrophil numbers. Flow cytometry was used to sort the resident and recruited macrophages. Post-treatment with MCTR1 offered dramatic benefits in the resolution phase of LPS-induced lung injury, including decreased neutrophil numbers, reduced BAL fluid protein and albumin concentrations and reduced histological injury. In addition, the expression of the M2 markers Arg1, FIZZ1, Remlα, CD206 and Dectin-1 was increased on resident macrophages in the LPS + MCTR1 group. Resident macrophage depletion abrogated the therapeutic effects of MCTR1, and reinjection of the sorted resident macrophages into the lung decreased neutrophil numbers. Finally, treatment with MCTR1 increased STAT6 phosphorylation. The STAT6 inhibitor AS1517499 abolished the beneficial effects of MCTR1. In conclusion, MCTR1 promotes resident M2 alveolar macrophage polarization via the STAT6 pathway to accelerate resolution of LPS-induced lung injury.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Polaridade Celular/fisiologia , Lipopolissacarídeos/farmacologia , Macrófagos Alveolares/metabolismo , Proteínas Oncogênicas/metabolismo , Fator de Transcrição STAT6/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Inflamação/metabolismo , Pulmão/metabolismo , Ativação de Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Transdução de Sinais/fisiologia
16.
Eur Spine J ; 29(4): 786-793, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32112152

RESUMO

PURPOSE: No study so far has paid attention to strabismus-related spinal imbalance. This study aimed to determine the epidemiology of thoracic scoliosis in children and adolescents with strabismus and investigate the association of two diseases. METHODS AND DESIGN: A cross-sectional study. Study group consists of 1935 consecutive candidates for strabismus surgery (4-18 years); Control group consists of the age- and sex-matched patients with respiratory diseases. All subjects underwent a screening program based on chest plain radiographs using the Cobb method. Their demographic information, clinical variables and results of Cobb angle were recorded and analyzed. RESULTS: A significantly higher prevalence of thoracic scoliosis (289/1935, 14.94% versus 58/1935, 3.00%) was found in study group compared with control group. Among strabismic patients, the coronal thoracic scoliosis curve mainly distributed in right and in main thoracic (198/289) and in the curves 10°-19° (224/289); Age range 7-9 years (103/1935), female (179/1935) and concomitant exotropia patients (159/851) were more likely to have thoracic scoliosis. According to the logistic regression, thoracic scoliosis had no significant association with age, BMI, duration of illness and onset age (p > 0.05). However, gender, BCVA, type of strabismus and degree of strabismus showed a significant relationship with the prevalence of thoracic scoliosis (p < 0.05). CONCLUSIONS: With a pooled prevalence of 14.94%, strabismus patients showed a great higher risk of developing thoracic scoliosis. Screening for scoliosis in strabismus patients can be helpful to discover a high prevalence of potential coronal scoliosis. More attention should be paid to ophthalmological problems in patients with scoliosis. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Escoliose , Fusão Vertebral , Estrabismo , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Escoliose/cirurgia , Estrabismo/epidemiologia , Estrabismo/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento
17.
Chin J Nat Med ; 17(10): 778-784, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31703758

RESUMO

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC50 39.6 ± 1.9 µmol·L-1) and HepG2 cells(IC50 41.5 ± 1.1 µmol·L-1), respectively. Compound 9 (23S, 24S)-24-[(O-ß-D-fucopyranosyl)oxy]-3ß, 23-dihydroxy-spirosta-5, 25(27)-diene-1ß-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[ß-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC50 33.6 ± 2.1 µmol·L-1).


Assuntos
Citotoxinas/química , Medicamentos de Ervas Chinesas/química , Helleborus/química , Esteroides/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxinas/isolamento & purificação , Citotoxinas/toxicidade , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Estrutura Molecular , Raízes de Plantas/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
18.
Int Immunopharmacol ; 76: 105877, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522017

RESUMO

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are life-threatening critical syndromes characterized by the infiltration of a large number of inflammatory cells that lead to an excessive inflammatory response. Resolvin D1 (RvD1), an endogenous lipid mediator, is believed to have anti-inflammatory and proresolving effects. In the present study, we examined the impact of RvD1 on the pulmonary inflammatory response, neutrophil influx, and lung damage in a murine model of lipopolysaccharide (LPS)-induced ALI. Treatment with RvD1 protected mice against LPS-induced ALI, and compared to untreated mice, RvD1-treated mice exhibited significantly ameliorated lung pathological changes, decreased tumor necrosis factor-α (TNF-α) concentrations and attenuated neutrophil infiltration. In addition, treatment with RvD1 attenuated LPS-induced neutrophil infiltration via the downregulation of CXCL2 expression on resident alveolar macrophages. Finally, BOC-2, which inhibits the RvD1 receptor lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2), reversed the protective effects of RvD1. These data demonstrate that RvD1 ameliorates LPS-induced ALI via the suppression of neutrophil infiltration by an ALX/FPR2-dependent reduction in CXCL2 expression on resident alveolar macrophages.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Quimiocina CXCL2/antagonistas & inibidores , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Macrófagos Alveolares/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Quimiocina CXCL2/genética , Quimiocina CXCL2/imunologia , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Macrófagos Alveolares/imunologia , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/efeitos dos fármacos
19.
Chin J Nat Med ; 17(8): 624-630, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472900

RESUMO

Five new polyhydroxylated furostanol saponins were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as tupistrosides J-N (1-5), together with four known furostanol saponins (6-9), on the basis of physico-chemical properties and spectral analysis. Among them, compounds 3 and 5 showed cytotoxicity against human cancer cell lines SW620 with IC50 values of 72.5 ± 2.4 and 77.3 ± 2.5 µmol·L-1, respectively. Compound 4 showed cytotoxicity against human cancer cell line HepG2 with IC50 value of 88.6 ± 2.1 µmol·L-1.


Assuntos
Antineoplásicos/química , Liliaceae/química , Saponinas/química , Esteróis/química , Células A549 , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/química , Rizoma/química , Saponinas/farmacologia , Esteróis/farmacologia
20.
Lab Invest ; 97(5): 543-554, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28218740

RESUMO

Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Canais Epiteliais de Sódio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Lipoxinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Animais , Lipopolissacarídeos , Pulmão/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Ubiquitina-Proteína Ligases Nedd4 , Alvéolos Pulmonares/metabolismo , Ratos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo
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