Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
Dig Dis Sci ; 69(6): 2096-2108, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653946

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver malignancy. Despite significant progress in HCC treatment, resistance to chemotherapy and tumor metastasis are the main reasons for the unsatisfactory prognosis of HCC. Circular RNAs (circRNAs) have been extensively documented to play a role in the development of various types of cancer. AIMS: Here, we investigated the role of DEAD-box helicase 17 circRNA (circDDX17) in HCC and its underlying molecular mechanisms. METHODS: Our research employed various techniques including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8), flow cytometry, dual luciferase reporter assay, RNA immunoprecipitation (RIP), and western blot analysis. Additionally, we conducted a tumor xenograft assay to investigate the in vivo function of circDDX17. RESULTS: Firstly, the expression of circDDX17 was downregulated in HCC tissues and cells. Through functional experiments, it was observed that the overexpression of circDDX17 enhanced the sensitivity of sorafenib, promoted apoptosis, and inhibited the process of epithelial-mesenchymal transition (EMT) in vitro. Additionally, in vivo studies revealed that circDDX17 reduced tumor growth and increased sorafenib sensitivity. Mechanically, circDDX17 competitively combined miR-21-5p to suppress PTEN expression and activate the PI3K/AKT pathway. Furthermore, our rescue assays demonstrated that circDDX17 act as a tumor suppressor by blocking sorafenib resistance and tumorigenesis, while the inhibitory effect caused by circDDX17 upregulation was neutralized when miR-21-5p was overexpressed, PTEN was silenced, or the PI3K/AKT pathway was activated. CONCLUSION: Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.


Asunto(s)
Carcinoma Hepatocelular , ARN Helicasas DEAD-box , Resistencia a Antineoplásicos , Neoplasias Hepáticas , ARN Circular , Sorafenib , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , ARN Circular/genética , ARN Circular/metabolismo , Resistencia a Antineoplásicos/genética , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinogénesis/genética , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Apoptosis/efectos de los fármacos , Masculino , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Acta Radiol ; 64(9): 2526-2534, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37464809

RESUMEN

BACKGROUND: Some peripheral small cell lung cancers (pSCLCs) and benign lung tumors (pBLTs) have similar morphological features but different treatment and prognosis. PURPOSE: To determine the significance of marginal vessels in differentiating pSCLCs and pBLTs. MATERIAL AND METHODS: A total of 57 and 95 patients with pathological confirmed nodular (≤3 cm) pSCLC and pBLT with similar morphological features were enrolled in this study retrospectively. The patients' clinical characteristics and computed tomography (CT) features of tumors and marginal vessels (vessels connecting with tumors) were analyzed and compared. RESULTS: Compared with pBLTs, pSCLCs had a larger diameter (P = 0.001) but lower enhancement (P = 0.015) and fewer had calcification (P = 0.013). Compared with pBLTs, more lesions had proximal (70.2% vs. 22.1%) and distal (59.6% vs. 4.2%) marginal vessels in pSCLCs (each P < 0.0001). In addition, in pSCLCs, the numbers of proximal (1.3 ± 1.4 vs. 0.3 ± 0.6), distal (2.4 ± 3.1 vs. 0.1 ± 0.5), and total (3.6 ± 3.5 vs. 0.4 ± 1.0) marginal vessels were all more than those in pBLTs (each P < 0.001). Receiver operating characteristic curve analysis revealed the positive distal marginal vessel sign had the highest specificity (95.8%), and the number of total marginal vessels had the best performance in discriminating pSCLC from pBLT (cutoff value = 1.5, AUC = 0.80, 95% CI = 0.72-0.89, sensitivity = 70.2%, and specificity = 91.6%). CONCLUSION: For peripheral solid nodules similar to pBLTs but without any calcification, the possibility of pSCLC should be considered if they have multiple marginal vessels (≥2), especially the distal ones.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Estudios Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Curva ROC
3.
Opt Lett ; 47(24): 6456-6459, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36538461

RESUMEN

Large deformation measurement is one of the main issues faced by the digital image correlation method, and the specially designed speckle pattern offers a promising solution. This Letter suggests an extremely simple method to fabricate an optimized speckle pattern for large deformation problems. It demonstrates a more effective large deformation initial estimation capability and measurement accuracy when combined with the pre-deformation assist strategy. A series of simulated and real experiments are used to test the effectiveness of the proposed method, and the results reveal that it performs significantly better than the traditional method in large deformation problems.

4.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5351-5361, 2021 Oct.
Artículo en Zh | MEDLINE | ID: mdl-34738439

RESUMEN

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P<0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1ß(IL-1ß), IL-6 and tumor necrosis factor α(TNF-α)(P<0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P<0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.


Asunto(s)
Medicamentos Herbarios Chinos , Sepsis , Animales , Ontología de Genes , Extractos Vegetales , Sepsis/tratamiento farmacológico , Sepsis/genética
5.
Appl Opt ; 59(35): 11123-11129, 2020 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-33361941

RESUMEN

The displacement hypothesis of eight-node cubic elements is selected as the shape function of digital volume correlation (DVC), and the Newton-Raphson iterative method is selected to solve the partial differential equation to measure the displacement field. In order to ensure that the DVC algorithm is usable under the large rotation condition, the spherical shell template matching technique is presented to perform the integer-voxel displacement searching for nodes, which can provide the optimal initial values for the Newton-Raphson iterative method due to the rotation and translation invariance of the spherical shell template. Simulated volume images are used to verify the reliability of the proposed method, and the results show that the proposed DVC method can be used to measure the deformation with an arbitrary rigid body rotation angle. This work is expected to be useful to measure deformation with large rotation of the internal structure of materials.

6.
Cytogenet Genome Res ; 157(4): 197-202, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30991391

RESUMEN

Uniparental disomy (UPD) is a rare type of chromosomal aberration that has sometimes been detected in paternity testing. We examined a 3-person family (father, mother, daughter) first by using short tandem repeat markers, which revealed 4 markers, TPOX, D2S1338, D2S1772, and D2S441, on chromosome 2 that were not transmitted in a Mendelian style. We then performed whole genome sequencing (WGS) to determine the range of the UPD. Chromosome 2 in the daughter showed a complete paternal UPD. To the best of our knowledge, this is the 4th case of complete paternal UPD of chromosome 2 with no clinical phenotype. Our study suggests that WGS, when performed to enhance the accuracy and reliability of parentage testing, can provide a powerful method to detect an UPD.


Asunto(s)
Pueblo Asiatico/genética , Repeticiones de Microsatélite , Disomía Uniparental/diagnóstico , Secuenciación Completa del Genoma/métodos , Adolescente , Cromosomas Humanos Par 2/genética , Padre , Femenino , Humanos , Masculino , Madres , Linaje , Disomía Uniparental/genética
7.
Appl Opt ; 58(25): 6873-6881, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31503662

RESUMEN

Considerable errors are encountered when the digital image correlation (DIC) method is used in a stress corrosion test. In this paper, the stress corrosion test system was built first. The applied maximum strain was accurately measured by DIC. Then, the effect of bubbles on DIC measurement results was analyzed. The bubbles induced additional errors in the measurement results, leading to local concentrations in measured displacement and strain fields. Finally, in order to reduce the displacement and strain errors caused by the bubbles, a twice subtraction method (TSM) was developed. The results of the application example show that TSM is an effective method to reduce the effect of bubbles on measurement accuracy of DIC for a stress corrosion test.

8.
Zhongguo Zhong Yao Za Zhi ; 44(24): 5336-5344, 2019 Dec.
Artículo en Zh | MEDLINE | ID: mdl-32237377

RESUMEN

Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.


Asunto(s)
Medicamentos Herbarios Chinos/efectos adversos , Frutas/toxicidad , Xanthium/toxicidad , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicina Tradicional China
9.
BMC Vet Res ; 14(1): 369, 2018 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-30482199

RESUMEN

BACKGROUND: MicroRNAs can regulate gene expression at the posttranscriptional level through translational repression or target degradation. Our previous investigations examined the differential expression levels of chi-miR-3031 in caprine mammary gland tissues in colostrum and common milk stages. RESULTS: The present study detected the role of chi-miR-3031 in the lactation mechanisms of GMECs. High-throughput sequencing was used to analyze transcriptomic landscapes of GMECs transfected with chi-miR-3031 mimics (MC) and a mimic negative control (NC). In the MC and NC groups, we acquired 39,793,503 and 36,531,517 uniquely mapped reads, respectively, accounting for 85.85 and 81.66% of total reads. In the MC group, 180 differentially expressed unigenes were downregulated, whereas 157 unigenes were upregulated. KEGG pathway analyses showed that the prolactin, TNF and ErbB signaling pathways, including TGFα, PIK3R3, IGF2, ELF5, IGFBP5 and LHß genes, played important roles in mammary development and milk secretion. Results from transcriptome sequencing, real-time PCR and western blotting showed that chi-miR-3031 suppressed the expression of IGFBP5 mRNA and protein. The expression levels of ß-casein significantly increased in the MC and siRNA-IGFBP5 groups. We observed that the down-regulation of IGFBP5 activated mTOR at the Ser2448 site in GMECs transfected with MC and siRNA-IGFBP5. Previous findings and our results showed that chi-miR-3031 activated the PI3K-AKT-mTOR pathway and increased ß-casein expression by down-regulating IGFBP5. CONCLUSIONS: These findings will afford valuable information for improving milk quality and contribute the development of potential methods for amending lactation performance.


Asunto(s)
Caseínas/metabolismo , Cabras/fisiología , Lactancia/fisiología , Glándulas Mamarias Animales/metabolismo , MicroARNs/metabolismo , Transducción de Señal , Animales , Células Epiteliales/metabolismo , Cabras/metabolismo , Lactancia/genética , Glándulas Mamarias Animales/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
10.
Cryobiology ; 81: 81-87, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29448018

RESUMEN

Intracellular ice formation (IIF) is the major cause of death in cells subjected to freezing. The occurrence of intracellular ice prevents the penetration of light into the camera and makes the image dark. Therefore, the gray-level variation can reflect the IIF. However, cell deformation is accompanied with IIF, especially for larger cells. It is necessary to account this entire phenomenon together in a single method. In this paper, the normalized parameter C defined by the gray-level variation depending on the displacement was defined to reflect the gray-level change of each pixel point in the region of interest of the image. The process of IIF of onion epidermal cells and 293T cells was analyzed by this method.


Asunto(s)
Microscopía por Crioelectrón/métodos , Criopreservación/métodos , Células Epiteliales/ultraestructura , Congelación , Procesamiento de Imagen Asistido por Computador/métodos , Células HEK293 , Humanos , Hielo , Cebollas , Grabación en Video
11.
Sensors (Basel) ; 18(11)2018 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-30441764

RESUMEN

Evaluation of impact damage to mango (Mangifera indica Linn) as a result of dropping from three different heights, namely, 0.5, 1.0 and 1.5 m, was conducted by hyperspectral imaging (HSI). Reflectance spectra in the 900⁻1700 nm region were used to develop prediction models for pulp firmness (PF), total soluble solids (TSS), titratable acidity (TA) and chroma (∆b*) by a partial least squares (PLS) regression algorithm. The results showed that the changes in the mangoes' quality attributes, which were also reflected in the spectra, had a strong relationship with dropping height. The best predictive performance measured by coefficient of determination (R²) and root mean square errors of prediction (RMSEP) values were: 0.84 and 31.6 g for PF, 0.9 and 0.49 oBrix for TSS, 0.65 and 0.1% for TA, 0.94 and 0.96 for chroma, respectively. Classification of the degree of impact damage to mango achieved an accuracy of more than 77.8% according to ripening index (RPI). The results show the potential of HSI to evaluate impact damage to mango by combining with changes in quality attributes.


Asunto(s)
Frutas/fisiología , Mangifera/fisiología , Algoritmos , Análisis de los Mínimos Cuadrados
12.
Opt Lett ; 42(21): 4247-4250, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-29088144

RESUMEN

Optical visualization of pathological changes in Alzheimer's disease (AD) can facilitate exploration of disease mechanisms and treatments. However, existing optical imaging methods have limitations on mapping pathological evolution in the whole mouse brain. Previous research indicated endogenous fluorescence contrast of senile plaques. Therefore, we develop cryo-micro-optical sectioning tomography (cryo-MOST) to capture intrinsic fluorescence distribution of senile plaques at a micrometer-level resolution in the whole brain. Validation using immunofluorescence demonstrates the capacity of cryo-MOST to visualize and distinguish senile plaques with competent sensitivity and spatial resolution. Compared with imaging in room temperature, cryo-MOST provides better signal intensity and signal-to-noise ratio. Using cryo-MOST, we obtained whole-brain coronal distribution of senile plaques in a transgenic mouse without exogenous dye. Capable of label-free brainwide visualization of Alzheimer's pathology, cryo-MOST may be potentially useful for understanding neurodegenerative disease mechanisms and evaluating drug efficacy.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/patología , Placa Amiloide , Tomografía Óptica , Enfermedad de Alzheimer/fisiopatología , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Relación Señal-Ruido
13.
Exp Parasitol ; 165: 95-102, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26993085

RESUMEN

Toxoplasma gondii (T. gondii) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T. gondii in vitro and in vivo. In our study, the anti-T. gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo, mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti-T. gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism.


Asunto(s)
Alcaloides/farmacología , Antiprotozoarios/farmacología , Quinolizinas/farmacología , Toxoplasma/efectos de los fármacos , Toxoplasmosis Animal/tratamiento farmacológico , Alcaloides/uso terapéutico , Alcaloides/toxicidad , Animales , Antiprotozoarios/uso terapéutico , Antiprotozoarios/toxicidad , Supervivencia Celular/efectos de los fármacos , Femenino , Células HeLa , Humanos , Concentración 50 Inhibidora , Hígado/química , Hígado/efectos de los fármacos , Hígado/parasitología , Hígado/patología , Ratones , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Quinolizinas/uso terapéutico , Quinolizinas/toxicidad , Sophora/química , Espiramicina/farmacología , Espiramicina/uso terapéutico , Espiramicina/toxicidad , Bazo/efectos de los fármacos , Bazo/parasitología , Bazo/patología , Tasa de Supervivencia , Toxoplasmosis Animal/mortalidad , Matrinas
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(6): 854-856, 2016 Dec 10.
Artículo en Zh | MEDLINE | ID: mdl-27984621

RESUMEN

OBJECTIVE: To report on a rare D13S317-off-ladder (OL) allele identified in an ethnic Han Chinese from Hainan. METHODS: The rare allele D13S317-OL was detected with a short tandem repeat (STR)-PCR method and DNA sequencing. RESULTS: The core repeat sequence of the rare allele was found to be [TATC]5. CONCLUSION: The rare D13S317-5 allele also exists among ethnic Hans from Hainan, which may have a significant value for personal identification and paternity testing.


Asunto(s)
Pueblo Asiatico/genética , Repeticiones de Microsatélite/genética , Alelos , Secuencia de Bases , Femenino , Humanos , Masculino , Paternidad , Reacción en Cadena de la Polimerasa/métodos
15.
Cell Biol Int ; 39(12): 1418-24, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26289388

RESUMEN

Dibenzocyclooctadiene lignans, the major active components of fruit of Schisandra chinensis (Turcz.) Baill., have been found to have activities that could prevent prostate and thyroid cancer, hepatotoxicity, oxidative stress-induced cerebral injury, etc. This study was conducted to evaluate the effects of seven dibenzocyclooctadiene lignans of Schisandra chinensis and explore the possible mechanisms in the human neuroblastoma SH-SY5Y cells exposed on serum and glucose deprivation (SGD) injury. The structure-activity relationships were also analyzed. Cell viability and lactate dehydrogenase (LDH) release were determined to evaluate cell injury. Inflammation and apoptosis-related protein levels were detected to elucidate the possible mechanisms. Schisantherin A, schizandrin C, and schizandrol B were found to have stronger protective effects than schizandrin A, schizandrin B, and schisanhenol in SH-SY5Y cells against SGD injury. Moreover, the protective effects of these lignans were possibly exhibited by regulating inflammation and apoptosis-related proteins in SH-SY5Y cells after SGD injury, supporting their beneficial effects for the prevention of cell injury in the pathogenesis of the central nervous system diseases, including ischemia stroke. The number and position of hydroxyl group and methylenedioxy in these lignans may be required for their effects.


Asunto(s)
Medio de Cultivo Libre de Suero/toxicidad , Ciclooctanos/farmacología , Glucosa/deficiencia , Lignanos/farmacología , Schisandra , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Ciclooctanos/aislamiento & purificación , Humanos , Lignanos/aislamiento & purificación
16.
Org Biomol Chem ; 13(26): 7257-64, 2015 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-26055070

RESUMEN

1-Benzyl-3-(substituted aryl)-5-methylfuro[3,2-c]pyrazole (YC-1) is a well-known synthetic compound with various satisfactory pharmacological activities, such as the activation of soluble guanylate cyclase (sGC) and the inhibition of hypoxia-induced factor-1α (HIF-1α). Recently, YC-1 has been demonstrated to have a potent activity on anti-fibrotic activity. However, the mechanism underlying its anti-fibrotic activity is still largely unknown. To this end, we presented here the design and synthesis of YC-1 and its novel derivatives, as well as the evaluation of their anti-fibrotic effects on activated human hepatic stellate cells (HSCs) LX-2. Moreover, the possible underlying mechanism of anti-fibrotic activity was also investigated for the first time by means of a CCK-8 assay, cell apoptosis analysis, and western blot analysis. Our study revealed that YC-1 and its derivatives suppressed activated LX-2 cell viability and induced cell apoptosis in a time- and dose-dependent manner. Western blot data demonstrated that these derivatives not only decreased the expression of α-smooth muscle actin (α-SMA), but also increased the expression of caspase-3, resulting in cell apoptosis. These findings strongly indicated that YC-1 and its derivatives, especially AC, could significantly inhibit LX-2 cell activation and induce LX-2 cell apoptosis by inhibiting α-SMA protein expression and promoting caspase-3 expression, respectively. In summary, our findings suggested that YC-1 derivatives might be potential agents for hepatic fibrosis therapy.


Asunto(s)
Diseño de Fármacos , Indazoles/síntesis química , Indazoles/farmacología , Cirrosis Hepática/tratamiento farmacológico , Actinas/metabolismo , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular , Supervivencia Celular , Técnicas de Química Sintética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Indazoles/química , Indazoles/uso terapéutico , Relación Estructura-Actividad
17.
Appl Opt ; 54(4): 934-9, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25967808

RESUMEN

A gray change detection method has been proposed to monitor damage in materials. The normalized parameter C has been defined by the displacement and the gray level value, which can reflect the gray change of each pixel point in the region of interest of the image. A zero deformation experiment has been done to discuss the feature of gray change caused by many factors except the damage. The results show that local expanded regions with concentrations of C can be considered as the damage regions. The uniaxial tensile experiments for an artificial rock specimen and a polycarbonate specimen have been done to verify the performance of the proposed method. The results show that the proposed method is effective for monitoring surface cracks in rocks and the shear band in polymers. This work provides a useful method for damage monitoring in materials.

18.
J Neurosci Res ; 92(7): 944-54, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24687774

RESUMEN

Mulberroside A is a natural polyhydroxylated stilbene compound present at relatively high abundance in the roots and twigs of Morus alba L. It is known for its nephroprotective, hypoglycemic, and antidiabetic effects. Because its metabolite, oxyresveratrol, possessed purported anti-inflammatory and neuroprotective effects, we proposed that mulberroside A may elicit neuroprotective effects that can be used in the treatment of brain ischemic injury. Therefore, we decided to investigate the pharmacological properties of mulberroside A in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion (OGD/R), evaluating its ability to counteract the hypoxia-ischemia impairment. The results showed that mulberroside A elicited neuroprotective effects comparable to nimodipine. The mechanistic studies showed that mulberroside A decreased the expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 and inhibited the activation of NALP3, caspase-1, and nuclear factor-κB and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38, exhibiting anti-inflammatory antiapoptotic effects. Our results also further demonstrate that the proinflammatory cytokines of IL-1ß, IL-6, and TNF-α are promising targets for treatment of cerebral ischemic injury. Although further investigation is required for its development, all of these findings led us to speculate that mulberroside A is a candidate for the treatment of ischemic stroke, which would act as a multifactorial neuroprotectant.


Asunto(s)
Corteza Cerebral/citología , Disacáridos/farmacología , Glucosa/deficiencia , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estilbenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteínas Portadoras , Caspasa 1/metabolismo , Hipoxia de la Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Embrión de Mamíferos , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos
19.
J Agric Food Chem ; 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37027486

RESUMEN

Flavonoids are a class of bioactive phytochemicals containing a core 2-phenylchromone skeleton and are widely found in fruits, vegetables, and herbs. Such natural compounds have gained significant attention due to their various health benefits. Ferroptosis is a recently discovered unique iron-dependent mode of cell death. Unlike traditional regulated cell death (RCD), ferroptosis is associated with excessive lipid peroxidation on cellular membranes. Accumulating evidence suggests that this form of RCD is involved in a variety of physiological and pathological processes. Notably, multiple flavonoids have been shown to be effective in preventing and treating diverse human diseases by regulating ferroptosis. In this review, we introduce the key molecular mechanisms of ferroptosis, including iron metabolism, lipid metabolism, and several major antioxidant systems. Additionally, we summarize the promising flavonoids targeting ferroptosis, which provides novel ideas for the management of diseases such as cancer, acute liver injury, neurodegenerative diseases, and ischemia/reperfusion (I/R) injury.

20.
J Ethnopharmacol ; 317: 116805, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37355082

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Growing evidence indicates that hyperuricemia is closely associated with gut microbiota dysbiosis. Orthosiphon aristatus (Blume) Miq. (O. aristatus), as a traditional Chinese medicine, has been widely used to treat hyperuricemia in China. However, the mechanism by which O. aristatus treats hyperuricemia has not been clarified. AIM OF THE STUDY: In this study, we investigated whether the molecular mechanism underlying the anti-hyperuricemia effect of O. aristatus is related to the regulation of gut microbiota by 16S rDNA gene sequencing combined with widely targeted metabolomics. MATERIALS AND METHODS: Hyperuricemia was induced in rats by administration of 10% fructose and 20% yeast, and the uricosuric effect was assessed by measuring the uric acid (UA) levels in serum and cecal contents. Intestinal morphology was observed by hematoxylin and eosin (HE) staining. To explore the effects of O. aristatus on the gut microbiota and its metabolites, we utilized 16S rDNA gene sequencing combined with widely targeted metabolomics. Furthermore, metabolic pathway enrichment analysis was performed on the screened differential metabolites. The real time quantitative polymerase chain reaction (RT-PCR) and western blotting (WB) were used to detect the expression of relevant proteins in the key pathway. RESULTS: Our results indicated that O. aristatus intervention decreased serum UA levels and increased the UA levels in cecal contents in hyperuricemic rats. Additionally, O. aristatus improved intestinal morphology and altered the composition of the gut microbiota and its metabolites. Specifically, 16S rDNA revealed that O. aristatus treatment significantly reduced the abundance of unidentified-Ruminococcaceae and Lachnospiraceae-NK4A136-group. Meanwhile, widely targeted metabolomics showed that 17 metabolites, including lactose, 4-oxopentanoate and butyrate, were elevated, while 55 metabolites, such as flavin adenine dinucleotide and xanthine, were reduced. Metabolic pathway enrichment analysis found that O. aristatus was mainly involved in purine metabolism. Moreover, RT-PCR and WB suggested that O. aristatus could significantly up-regulate the expression of UA excretion transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the intestine. CONCLUSION: O. aristatus exerts UA-lowering effect by regulating the gut microbiota and ABCG2 expression, indicating that this herb holds great promise in the treatment of hyperuricemia.


Asunto(s)
Microbioma Gastrointestinal , Hiperuricemia , Orthosiphon , Ratas , Animales , Orthosiphon/química , Orthosiphon/metabolismo , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Intestinos , Ácido Úrico/metabolismo , Metabolómica
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA