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1.
Technol Health Care ; 32(S1): 313-320, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38669497

RESUMEN

BACKGROUND: With the widespread use of low-dose spiral computed tomography (LDCT) and increasing awareness of personal health, the detection rate of pulmonary nodules is steadily rising. OBJECTIVE: To evaluate the success rate and safety of two different models of Hook-Wire needle localization procedures for pulmonary small nodule biopsy. METHODS: Ninety-four cases with a total of 97 pulmonary small nodules undergoing needle localization biopsy were retrospectively analyzed. The cases were divided into two groups: Group A, using breast localization needle steel wire (Bard Healthcare Science Co., Ltd.); Group B, using disposable pulmonary nodule puncture needle (SensCure Biotechnology Co., Ltd.). All patients underwent video-assisted thoracoscopic surgery (VATS) for nodule removal on the same day after localization and biopsy. The puncture localization operation time, success rate, complications such as pulmonary hemorrhage, pneumothorax, hemoptysis, and postoperative comfort were observed and compared. RESULTS: In Group A, the average localization operation time for 97 nodules was 15.47 ± 5.31 minutes, with a success rate of 94.34%. The complication rate was 71.69% (12 cases of pneumothorax, 35 cases of pulmonary hemorrhage, 2 cases of hemoptysis), and 40 cases of post-localization discomfort were reported. In Group B, the average localization operation time was 25.32 ± 7.83 minutes, with a 100% success rate. The complication rate was 29.55% (3 cases of pneumothorax, 15 cases of pulmonary hemorrhage, 0 cases of hemoptysis), and 3 cases reported postoperative discomfort. According to the data analysis in this study, Group B had a lower incidence of puncture-related complications than Group A, along with a higher success rate and significantly greater postoperative comfort. CONCLUSIONS: The disposable pulmonary nodule puncture needle is safer and more effective in pulmonary small nodule localization biopsy, exhibiting increased comfort compared to the breast localization needle. Additionally, the incidence of complications is significantly lower.


Asunto(s)
Nódulo Pulmonar Solitario , Cirugía Torácica Asistida por Video , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/métodos , Cirugía Torácica Asistida por Video/instrumentación , Nódulo Pulmonar Solitario/cirugía , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/diagnóstico por imagen , Anciano , Adulto , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Biopsia con Aguja/métodos , Biopsia con Aguja/instrumentación , Agujas , Tempo Operativo , Tomografía Computarizada Espiral/métodos
2.
J Biomol Struct Dyn ; : 1-18, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37668086

RESUMEN

As a pivotal node in modulating various cell behaviors, Rho-associated kinase-1 (ROCK1) has attracted significant attention as a promising therapeutic target in a variety of diseases. Benzamide has been widely reported as a ROCK1 inhibitors in recent years. To better understand its pharmacological properties and to explore its potential inhibitors, a series of ROCK1 inhibitors derived from N-methyl-4-(4-pyrazolidinyl) benzamides (MPBs) were investigated by using three-dimensional quantitative structure-activity relationship (3D-QSAR) models, pharmacophore models, molecular docking, and molecular dynamics (MD) simulation. The comparative Molecular Field Analysis (CoMFA) model (q2 = 0.616, R2 = 0.972, ONC = 4, and r2pred = 0.983) and the best Comparative Molecular Similarity Indices Analysis (CoMSIA) model (q2= 0.740, R2 = 0.982, ONC = 6, and r2pred = 0.824) exhibited reliable predictability with satisfactory validation parameters. In the subsequent virtual screening, VS03 and VS05 were identified to have superior predicted activities and higher docking scores, meanwhile they demonstrated to be reasonably stable in the binding pocket through MD simulations. These results provide a significant theoretical direction for the rational design and development of novel ROCK1 inhibitors.Communicated by Ramaswamy H. Sarma.

3.
JGH Open ; 7(6): 419-423, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37359110

RESUMEN

Background and Aim: A pyogenic liver abscess (PLA) is an infectious disease with high in-hospital mortality. It has no specific symptoms and is difficult to be diagnosed early in the emergency department. Ultrasound is commonly used to detect PLA lesions of PLA, but its sensitivity can be affected by lesion size, location, and clinician experience. Therefore, early diagnosis and prompt treatment (especially abscess drainage) are crucial for better patient outcomes and should be prioritized by clinical physicians. Methods: We conducted a retrospective study to compare the effect of early and late (i.e., receiving CT scanning within 48 h and >48 h after admission) adoption of nonenhanced computed tomography (CT) scanning regarding the hospitalization days and interval between admission and drainage of patients with PLA. Results: This study included 76 hospitalized patients with PLA in the Department of Digestive Disease of Xiamen Chang Gung Hospital in China who underwent CT examinations from 2014 to 2021. We conducted CT scans on 56 patients within 48 h of admission and on 20 patients more than 48 h after admission. The early CT group had a significantly shorter hospitalization length compared with the late CT group (15.0 days vs. 20.5 days; P = 0.035). Besides, the median time to initiate drainage after admission was also significantly shorter in the early CT group than in the late CT group (1.0 days vs. 4.5 days; P < 0.001). Conclusion: Early CT scanning within 48 h of admission may aid in early PLA diagnosis and benefit disease recovery, as revealed by our findings.

4.
Chin J Traumatol ; 26(3): 125-130, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36990837

RESUMEN

The wound mechanism, injury characteristics and treatment principles of anti-armored vehicle ammunition against armored crew in the past 20 years are summarized in this paper. Shock vibration, metal jet, depleted uranium aerosol and post armor breaking effect are the main factors for wounding armored crew. Their prominent characteristics are severe injury, high incidence of bone fracture, high rate of depleted uranium injury, and high incidence of multiple/combined injuries. During the treatment, attention must be paid on that the space of armored vehicle is limited, and the casualties should be moved outside of the cabin for comprehensive treatment. Especially, the management of depleted uranium injury and burn/inhalation injury are more important than other injuries for the armored wounds.


Asunto(s)
Quemaduras , Traumatismo Múltiple , Uranio , Humanos , Uranio/análisis , Aerosoles y Gotitas Respiratorias , Vehículos a Motor , Quemaduras/terapia
5.
Chin J Traumatol ; 26(3): 139-146, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36344366

RESUMEN

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION: The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.


Asunto(s)
Traumatismos por Explosión , Lesión Pulmonar , Animales , Lesión Pulmonar/etiología , Cabras , Explosiones , Pulmón/patología
6.
Pharmacol Res ; 187: 106636, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36586643

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and limited therapeutic options. The immune checkpoint PD1/PD-L1 axis is related to the pathogenesis of pulmonary fibrosis, and upregulated expression levels of PD-L1 have been demonstrated in IPF patients. However, the mechanism of PD-L1 in pulmonary fibrosis is not fully understood. Here, we demonstrated upregulated expression of PD-L1 in fibrotic lung tissues and sera of IPF patients. Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs). Silencing PD-L1 attenuated BLM-induced EMT and fibrosis-like morphology changes in HPAEpiCs. In addition, we identified that PD-L1 directly binds to vimentin and inhibits vimentin ubiquitination, thereby increasing vimentin levels in HPAEpiCs. Silencing of vimentin inhibited BLM- and PD-L1-induced fibrosis in HPAEpiCs. The correlation between PD-L1 and EMT or vimentin expression was further confirmed in clinical samples and animal models. Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.


Asunto(s)
Antígeno B7-H1 , Fibrosis Pulmonar Idiopática , Animales , Humanos , Regulación hacia Arriba , Vimentina/genética , Vimentina/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Pulmón , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Transición Epitelial-Mesenquimal , Bleomicina
7.
Am J Cancer Res ; 11(7): 3575-3593, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34354861

RESUMEN

Human hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Tumor-specific pyruvate kinase M2 (PKM2) is essential for cancer metabolism and tumorigenesis. Shikonin, a specific inhibitor of PKM2, but not PKM1, exhibits significant anticancer effect in HCC, and was deemed as a promising drug for cancer therapy. However, shikonin-mediated bypass signaling in HCC remained unclear. Here, we performed forward/reverse stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics to identify the early molecular events controlled by shikonin. We demonstrated for the first time that shikonin could induce the nuclear translocation of PKM2 for recruiting Nrf2, and transcriptionally activated Nrf2 downstream target gene BAG3, therefore increasing protective effect to sustain cell survival. Knockdown of BAG3 by si-RNA significantly potentiated the anticancer effect of shikonin. These findings provided the first evidence of a new noncanonical function of inhibited PKM2 could act as a transcriptional coactivator of Nrf2 in cancer survival, highlight that shikonin in combined with BAG3 inhibitor could be a promising therapeutic strategy for HCC therapy.

8.
Ecotoxicol Environ Saf ; 224: 112634, 2021 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-34392153

RESUMEN

Nickel is a heavy metal element extensively distributed in the environment and widely used in modern life. Divalent nickel is one of the most widespread forms of nickel and has been reported as toxic to various tissues. However, whether exposure to divalent nickel negatively affects ovarian homeostasis and oocyte quality remains unclear. In this study, we found that 3 weeks of nickel sulfate exposure affected body growth and decreased the weight and coefficient of the ovary, and increased atretic follicles exhibiting enhanced apoptosis in granulosa cells. Further studies have found that nickel sulfate triggered ovarian fibrosis and inflammation via transforming growth factor-ß1 and nuclear factor-κB pathways, and reduced oocyte development ability. In addition, nickel sulfate increased the level of reactive oxygen species, which induced DNA damage and early apoptosis. Moreover, it was found that nickel sulfate caused damage to the mitochondria showing aberrant morphology, distribution and membrane potential while decreased levels of histone methylation. To summarize, our results indicated that nickel sulfate exposure triggered ovarian fibrosis and inflammation and caused structural and functional disorders of mitochondria in oocytes, which consequently disturbed ovarian homeostasis and follicle development and decreased oocyte quality.

9.
Comb Chem High Throughput Screen ; 23(9): 955-971, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32407262

RESUMEN

BACKGROUND AND OBJECTIVE: Mycoplasmal pneumonia (MP) can lead to inflammation, multiple system immune damage, and mixed infection in children. The pathogenesis is still unclear. Shuang-Huang-Lian (SHL) oral liquid can treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. However, our current understanding of the molecular mechanisms supporting its clinical application still lags behind due to the lack of researches. It is difficult to understand the overall sensitization mechanism of SHL oral liquid. The purpose is to explain the mechanism of action of drugs in this study, which is useful to ensure the safety of medication for children. METHODS: The therapeutic mechanism of SHL oral liquid was investigated by a system pharmacology approach integrating drug-likeness evaluation, oral bioavailability prediction, ADMET, protein-protein interaction worknet, Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes database pathway performance, C-T-P network construction and molecular docking. RESULTS: A total of 18 active ingredients contained in SHL oral liquid and 53 major proteins were screened out as effective players in the treatment of M. pneumoniae disease through some related pathways and molecular docking. The majority of targets, hubs and pathways were highly related to anti-mycoplasma therapy, immunity and inflammation process. CONCLUSION: This study shows that the anti-bacterial effect of SHL oral liquid has multicomponent, multi-target and multi-pathway phenomena. The proposed approach may provide a feasible tool to clarify the mechanism of traditional Chinese medicines and further develop their therapeutic potentials.


Asunto(s)
Antiinfecciosos/química , Medicamentos Herbarios Chinos/química , Neumonía por Mycoplasma/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas/química , Antiinfecciosos/farmacocinética , Bases de Datos Genéticas , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacocinética , Regulación de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Unión Proteica , Transducción de Señal , Bibliotecas de Moléculas Pequeñas/farmacología
10.
Zhongguo Zhong Yao Za Zhi ; 44(18): 3924-3934, 2019 Sep.
Artículo en Chino | MEDLINE | ID: mdl-31872726

RESUMEN

Lotus( Nelumbo nucifera) is a traditional medicinal plant,and nowadays it is regarded both as medicine and food. It is widespread across China and rich in natural resources. Almost every part of N. nucifera could be used for medical or edible purpose,including seeds( Lianzi),black ripe fruits( Shilianzi),seed coats( Lianyi),green embryos of mature seed( Lianzixin),flowers( Lianhua),stamens( Lianxu),receptacles( Lianfang),leaves( Heye),leaf or flower stalks( Hegeng),leaf bases( Heyedi),rhizomes( Ou) and rhizome nodes( Oujie). Therefore,this plant is praised as a commercial crop with great economic values. Isoquinoline type alkaloids are the main chemical components of lotus. Smooth muscles usually exist in the digestive tract,respiratory tract and vascular,urinary,reproductive and other human systems. Dysfunction of smooth muscle contraction will induce many diseases including hypertension,asthma and gastrointestinal disorder,etc.,and most of current therapeutic strategies rely on relaxation of smooth muscle by drugs.Previous studies have shown that alkaloids of lotus have strong relaxation activity on smooth muscle. The present paper reviews phytochemistry and smooth muscle relaxation activity of 59 isoquinoline alkaloids from N. nucifera through accessing CNKI,PubMed and multiple databases for biomedical sciences.


Asunto(s)
Alcaloides/farmacología , Isoquinolinas/farmacología , Relajación Muscular , Músculo Liso/efectos de los fármacos , Nelumbo/química , China , Humanos , Fitoquímicos/farmacología , Extractos Vegetales
11.
Front Pharmacol ; 10: 979, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31572175

RESUMEN

Smooth muscle (SM) contraction is one of the important physiological functions of the human body, and SM abnormal contraction will induce many diseases. The phosphorylated regulatory light chains (p-RLC) play a decisive role in SM contraction, and dephosphorylation of p-RLC is an effective way to relax SM. Our previous study showed that the novel benzylisoquinoline alkaloid, neoliensinine (Neo), could relax microvascular SM contracted by KCl hyperpolarization. In this study, mesenteric capillaries isolated from 45 mice were divided into normal tension group (Control), 124 mM KCl induced contraction model group (Model), and KCl and Neo-treatment group (Drug). The dephosphorylation levels of RLC in the three groups were measured. Compared with the model group, the phosphorylation of RLC in the drug group was decreased dramatically as expected, suggesting that the relaxation effect of Neo was caused by downregulating p-RLC of microvessel SM. In order to fully understand its fundamental mechanism, our research focused on the identification of target proteins in mice with KCl-induced contractile mesenteric capillary. Isobaric tags for relative and absolute quantification (ITRAQ) tagging was carried out by nanospray liquid chromatography-tandem mass spectrometry. The results allowed the upregulation of 164 differential abundance proteins (DAPs) among the 3,474 protein abundance disturbances identified from the model/control samples. Further comparison showed that there were 16 DAP convergences associated with vascular SM contraction between the drug/model and the drug/control samples. Among them, two proteins with known function, PLCß and RhoGEF12, were selected as target proteins of the relaxation effect of Neo. The two selective target DAPs were verified by Western blot at protein level. The results suggested that changes of the two proteins were consistent with that of the iTRAQ results. Our present work reveals that Neo relaxes vascular smooth muscle via inhibition of RLC phosphorylation, and PLCß and RhoGEF12 may be potential biomarkers for evaluating the effects mediated by Neo.

12.
J Trauma Acute Care Surg ; 87(6): 1336-1345, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31389921

RESUMEN

BACKGROUND: Vascular dysfunction is a major cause of sepsis-induced multiple-organ dysfunction. Resveratrol is a polyphenol compound with extensive pharmacological effects including anti-inflammation. The aim of this study was to determine the role and mechanism of resveratrol in protecting vascular function following sepsis. METHODS: The cecal ligation and puncture method was used to establish a septic shock rat model. Resveratrol (5 mg/kg and 10 mg/kg) was administered intravenously immediately and at 12 hours after cecal ligation and puncture, respectively. The effects of resveratrol on vasodilatation function, blood flow velocity, hemodynamics, and vital organ function and its relationship to Rac-1 and HIF-1α were observed. RESULTS: Vascular relaxation reactivity and blood flow velocity were significantly decreased after septic shock, both were significantly improved by resveratrol 5 mg/kg and 10 mg/kg, and the effect of 10 mg/kg was greater. The relaxation reactivity of the superior mesenteric artery to acetylcholine (Ach) was increased by 43.2%. The blood flow velocity of mesenteric arterioles and venules was increased by 47.1% and 51%, respectively, after resveratrol (10 mg/kg) administration compared with the septic shock group. The hemodynamics and both liver and kidney blood flow were significantly decreased after septic shock, which were significantly improved them by resveratrol, which enhanced the vascular relaxation reactivity in septic shock rats. The 72-hour survival rate of septic shock rats in the resveratrol group (62.5%) was significantly higher than that in the septic shock group (6.3%). Resveratrol significantly upregulated the expression of endothelial nitric oxide synthase (eNOS) and downregulated the expression of inducible NOS, Rac-1, and HIF-1α. Inhibitors of Rac-1 and HIF-1α significantly improved the expression of eNOS, and inhibition of eNOS (L-NAME, 5 mg/kg) antagonized the resveratrol-induced improvement in vascular relaxation reactivity and survival. CONCLUSION: Resveratrol was beneficial for vasodilatation function in rats with septic shock, which is the major contribution to resveratrol improving hemodynamics and organ perfusion. The mechanism involved resveratrol upregulating the expression of eNOS by inhibiting Rac-1 and HIF-1α.


Asunto(s)
Resveratrol/farmacología , Choque Séptico/fisiopatología , Vasodilatación/efectos de los fármacos , Animales , Velocidad del Flujo Sanguíneo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Hemodinámica/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/irrigación sanguínea , Hígado/irrigación sanguínea , Masculino , Microcirculación/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismo , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Resveratrol/uso terapéutico , Choque Séptico/tratamiento farmacológico , Choque Séptico/metabolismo , Circulación Esplácnica/efectos de los fármacos , Regulación hacia Arriba , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Proteína de Unión al GTP rac1/metabolismo
13.
Chem Commun (Camb) ; 55(28): 4059-4062, 2019 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-30882124

RESUMEN

Two new 2D Zn(ii) metal-organic frameworks (MOFs) {[Zn2(L)2(µ2-O)(H2O)3]·3DMA}n (Zn-1) and [Zn2(L)2(2,2'-bipy)(µ2-O)(H2O)2]n (Zn-2) (H2L = 2,5-thiophene dicarboxylic acid, bipy = 2,2'-dipyridyl) were designed and synthesized. Through the strategy of introducing bipy as a "lock", Zn-1 was transferred to Zn-2via a crystal-to-crystal process, which showed significantly enhanced solvent and air stability compared to that of Zn-1. Without post modification, Zn-2 was used as an electrode modified material to construct sensors for the electrochemical recognition and distinction of S-containing amino acids, including l-cysteine, l-methionine and l-cystine.

14.
Mol Carcinog ; 58(1): 55-65, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30182377

RESUMEN

Liver cancer stem cells (CSCs) were involved in tumorigenesis, progression, recurrence, and drug resistance of hepatocellular carcinoma (HCC). miR-365 was downregulated in hepatocellular carcinoma and inhibited HCC cell proliferation and invasion. However, the role of miR-365 in liver cancer stem cells was unknown. Herein, we observed a remarkable decrease of miR-365 expression in CD133 or EpCAM-positive liver CSCs as well as in CSC-enriched hepatoma spheres. Up-regulated miR-365 suppressed liver CSC expansion by inhibiting the dedifferentiation of hepatoma cells and decreasing the self-renewal ability of liver CSCs. Mechanistically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in hepatoma cells downregulated the RAC1 mRNA and protein expression. RAC1 also could promote the expansion of liver CSCs. The special RAC1 inhibitor EHop-106 or RAC1 overexpression abolished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-365 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-365-suppressed liver CSCs expansion. miR-365 was downregulated in liver CSCs and could inhibit HCC cells dedifferentiation and liver CSCs expansion by targeting RAC1 signaling.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , MicroARNs/genética , Células Madre Neoplásicas/patología , Proteína de Unión al GTP rac1/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/metabolismo , Pronóstico , Células Tumorales Cultivadas , Proteína de Unión al GTP rac1/genética
15.
J Vis Exp ; (138)2018 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-30176012

RESUMEN

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.


Asunto(s)
Contracción Isométrica/fisiología , Arterias Mesentéricas/fisiopatología , Miografía/métodos , Animales , Masculino , Ratones
16.
Inorg Chem ; 57(20): 12475-12479, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30256113

RESUMEN

Two new iron(II) complexes with 1D chain and 2D network structures have been successfully synthesized and characterized. One of the complexes exhibits a pressure-induced spin-crossover property with a reversible color change from white to purple at room temperature. The special property makes it a suitable candidate as a pressure sensor.

17.
Fitoterapia ; 124: 58-65, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29108933

RESUMEN

A new skeleton benzylisoquinoline (BI) named neoliensinine (1) was isolated from embryos of lotus seed (Nelumbo nucifera Gaertn.), a traditional Chinese herb. The tribenzylisoquinoline (TBI) structure of 1 was confirmed by interpreting spectroscopic data of UV, IR, MS, 1D and 2D NMR. The stereo-configurations of the new compound, together with two known bisbenzylisoquinolines (BBI), neferine and isoliensinine were established by analyzing 1H NMR and 13C NMR spectra. The relaxation of 1, neferine, isoliensinine and liensinine in isolated mesenteric vascular smooth muscle (VSM) was evaluated. All the four BIs could efficiently inhibit MVSM contraction induced by 124mM KCl, with IC50 values of 2.407µM (1), 1.169µM (neferine), 3.504µM (isoliensinine) and 3.583µM (liensinine), respectively, suggesting that they were all potential relaxants for abnormal smooth muscle contractions. Interestingly, VSM treated by the three BBIs could re-contract when being stimulated by KCl after the drugs were removed, while VSM dealt with the TBI couldn't. It indicated that 1 has much high affinity with the molecular targets on relaxation of VSM contraction, which may relate to the unique skeleton with three BI groups.


Asunto(s)
Alcaloides/aislamiento & purificación , Músculo Liso/efectos de los fármacos , Nelumbo/química , Fármacos Neuromusculares/aislamiento & purificación , Animales , Bencilisoquinolinas/aislamiento & purificación , Femenino , Técnicas In Vitro , Isoquinolinas/aislamiento & purificación , Masculino , Ratones Endogámicos C57BL , Estructura Molecular , Fenoles/aislamiento & purificación , Semillas/química
18.
Inorg Chem ; 56(6): 3414-3420, 2017 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-28263612

RESUMEN

The materials Ag@MIL-100(Fe) and Ag@UIO-66(Zr) are obtained for the capture and transformation of CO2 into alkynyl carboxylic acids, which are environmental friendly, facile to synthesize, and exhibit excellent efficiency and reusability. The influence on the catalytic activity of such Ag@MOF systems by metal-organic frameworks' (MOFs) surface area, thermal, and chemical stability, especially the acid-base characteristics of the pores, are compared and discussed systematically.

19.
Ying Yong Sheng Tai Xue Bao ; 27(11): 3698-3704, 2016 Nov 18.
Artículo en Chino | MEDLINE | ID: mdl-29696870

RESUMEN

To evaluate the sublethal effects of spinetoram and azadirachtin on western flower thrips, Frankliniella occidentalis, leaf dipping method was used to determine their sublethal concentrations (LC25) on the 2nd instar nymph, and their influences on development and reproduction of F. occidentalis were studied. The results showed exposure of sublethal concentrations of spinetoram and azadirachtin to F. accidentalis had different degrees of effects on this insect pest. Under bisexual reproduction, the LC25 spinetoram had no significant influences on pre-oviposition period, female adult longevity and fecundity, but male adult longevity was significantly shorter than the control. The LC25 azadirachtin significantly reduced fecundity and prolonged pre-oviposition period. Under parthenogenesis, the LC25 spinetoram and azadirachtin extended the pre-oviposition duration, whereas the LC25 azadirachtin shortened the female adult longevity and significantly decreased fecundity. The LC25 spinetoram and azadirachtin had different influences on developmental duration of each stage of next generation. The immature stage in treatment group of the LC25 spinetoram was shorter than that in treatment group of the LC25 azadirachtin, under bisexual reproduction or parthenogenesis. Intrinsic rate of increase (rm) and finite rate of increase (λ) of population treated by the LC25 spinetoram were higher than those of the control, whereas the rm, R0, and λ of population treated by the LC25 azadirachtin were lower than those of the control. The findings indicated that the effects of the LC25 spinetoram and azadirachtin on the development and reproduction of F. accidentalis were different. The LC25 spinetoram had certain stimulating effect, whereas the LC25 azadirach-tinon had significant inhibitory effect. Two biopesticides' influences were related with the reproductive patterns of F. accidentalis.


Asunto(s)
Insecticidas , Limoninas , Macrólidos , Thysanoptera/fisiología , Animales , Femenino , Fertilidad , Longevidad , Masculino , Reproducción
20.
Am J Physiol Lung Cell Mol Physiol ; 309(11): L1323-32, 2015 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-26342084

RESUMEN

Connexin (Cx)43 has been shown to participate in several cardiovascular diseases. Increased vascular permeability is a common and severe complication in sepsis or septic shock. Whether or not Cx43 takes part in the regulation of vascular permeability in severe sepsis is not known, and the underlying mechanism has not been described. With cecal ligation and puncture-induced sepsis in rats and lipopolysaccharide (LPS)-treated vascular endothelial cells (VECs) from pulmonary veins, the role of Cx43 in increased vascular permeability and its relationship to the RhoA/Rock1 pathway were studied. It was shown that vascular permeability in the lungs, kidneys, and mesentery in sepsis rats and LPS-stimulated monolayer pulmonary vein VECs was significantly increased and positively correlated with the increased expression of Cx43 and Rock1 in these organs and cultured pulmonary vein VECs. The connexin inhibitor carbenoxolone (10 mg/kg iv) and the Rock1 inhibitor Y-27632 (2 mg/kg iv) alleviated the vascular leakage of lung, mesentery, and kidney in sepsis rats. Overexpressed Cx43 increased the phosphorylation of 20-kDa myosin light chain (MLC20) and the expression of Rock1 and increased the vascular permeability and decreased the transendothelial electrical resistance of pulmonary vein VECs. Cx43 RNA interference decreased the phosphorylation of MLC20 and the expression of Rock1 and decreased LPS-stimulated hyperpermeability of cultured pulmonary vein VECs. The Rock1 inhibitor Y-27632 alleviated LPS- and overexpressed Cx43-induced hyperpermeability of monolayer pulmonary vein VECs. This report shows that Cx43 participates in the regulation of vascular permeability in sepsis and that the mechanism is related to the Rock1-MLC20 phosphorylation pathway.


Asunto(s)
Permeabilidad Capilar , Conexina 43/metabolismo , Cadenas Ligeras de Miosina/inmunología , Sepsis/metabolismo , Sepsis/fisiopatología , Quinasas Asociadas a rho/metabolismo , Animales , Ciego/patología , Células Endoteliales/metabolismo , Femenino , Interleucina-6/sangre , Riñón/irrigación sanguínea , Lentivirus/metabolismo , Ligadura , Lipopolisacáridos , Pulmón/irrigación sanguínea , Masculino , Mesenterio/irrigación sanguínea , Peso Molecular , Fosforilación , Proteína Quinasa C/metabolismo , Venas Pulmonares/patología , Punciones , Interferencia de ARN , Ratas Sprague-Dawley , Sepsis/sangre , Transducción de Señal , Fibras de Estrés/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Proteína de Unión al GTP rhoA/metabolismo
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