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OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.
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Neoplasias del Cuello Uterino , Femenino , Niño , Humanos , Neoplasias del Cuello Uterino/patología , Quimioradioterapia/efectos adversos , Ganglios Linfáticos/patología , Supervivencia sin Enfermedad , Escisión del Ganglio Linfático , Estudios Retrospectivos , Estadificación de Neoplasias , HisterectomíaRESUMEN
To assess the application potential of sewage sludge biochar produced by industrial-scale pyrolysis (ISB), the release characteristics of nutrients (NH4+, PO43-, K, Ca, Mg and Fe) and heavy metals (Mn, Cu, Zn, Pb, Ni and Cr) were investigated. Their release amounts increased with decreasing initial pH and increasing solid-liquid ratios (RS-L) and temperature. The release types of NH4+, K, Mg, and Mn were diffusion/dissolution, while those of Cu, Zn, Pb, Ni, and Cr were diffusion/resorption. The release types of PO43- and Ca varied with initial pH and RS-L, respectively. The chemical actions played dominant roles in their release, while particle surface diffusion and liquid film diffusion determined the rates of diffusion and resorption phases, respectively. The release of NH4+, PO43-, K, Ca, Mg, Mn and Zn was a non-interfering, spontaneous (except PO43-), endothermic, and elevated randomness process. The release efficiency of NH4+, PO43- and K met the Chinese standard for slow-release fertilizers, while the total risk of ISB was low. The eutrophication and potential ecological risks of ISB were acceptable when the dose was less than 3 g L-1 and the initial pH was no lower than 3. In conclusion, ISB had potential as a slow-release fertilizer and adsorbent.
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Carbón Orgánico , Fertilizantes , Metales Pesados , Nutrientes , Pirólisis , Aguas del Alcantarillado , Fertilizantes/análisis , Metales Pesados/análisis , Aguas del Alcantarillado/química , Carbón Orgánico/química , Nutrientes/análisis , Adsorción , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisisRESUMEN
Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized almost every habitat on Earth. Here we report the draft genome sequence of Apostasia shenzhenica, a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel third-generation genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms.
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Evolución Molecular , Genoma de Planta/genética , Orchidaceae/genética , Filogenia , Genes de Plantas/genética , Orchidaceae/anatomía & histología , Orchidaceae/clasificación , TranscriptomaRESUMEN
BACKGROUND: Numerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable. OBJECTIVE: To assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning. METHODS: Forty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT). RESULTS: Eleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up. CONCLUSION: RNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics.
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Precursores del ARN , Empalme del ARN , Femenino , Asesoramiento Genético , Pruebas Genéticas/métodos , Humanos , Embarazo , Diagnóstico Prenatal , Empalme del ARN/genéticaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the therapeutic value and treatment-related complications of adjuvant chemotherapy after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). DESIGN: The medical records of LACC patients who underwent CCRT were reviewed retrospectively. METHODS: A total of 1,138 patients with LACC who had been treated at our hospital between January 2013 and December 2017 were included in the study and classified into two groups: the CCRT group, comprising 726 patients who had received only CCRT, and the CCRT + adjuvant chemotherapy (ACT) group, comprising 412 patients who had received three cycles of adjuvant chemotherapy after CCRT. 39 patients in the CCRT group and 50 patients in the CCRT + ACT group had undergone lymphadenectomy, which revealed pathology-positive lymph nodes in 22 patients and 35 patients, respectively. Progression-free survival (PFS), overall survival (OS), and adverse events were compared. RESULTS: The median follow-up time was 61 months (range: 2-96 months). No significant differences in PFS and OS were found between the two groups (p > 0.05), but more grade 3-4 acute hematologic toxicities were observed in the CCRT + ACT group than in the CCRT group (24.8% vs. 31.8%, p = 0.01). A subgroup analysis of patients with pathology-positive lymph nodes showed that the 5-year PFS and OS rates were 76.5% and 74.9%, respectively, for the CCRT + ACT group and 45.0% and 49.2%, respectively, for the CCRT group; the differences were statistically significant (p = 0.015 and 0.042, respectively). LIMITATIONS: First, the sample size of the subgroup of patients with pathology-positive lymph nodes was too small for a confirmative conclusion. The heterogeneous population and the selection bias resulting from the retrospective design were the other flaws of our study. CONCLUSION: The application of adjuvant chemotherapy after CCRT may be worth investigating further for women with LACC and pathology-positive lymph nodes, but this approach is associated with an increase in acute hematology toxicities.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Neoplasias del Cuello Uterino/terapia , Quimioradioterapia , Quimioterapia Adyuvante , HospitalesRESUMEN
Immunotherapy has provided a promising strategy for the treatment of cancers. However, even in tumors with high antigen burdens, the systemic inhibition of the antigen presentation still greatly restricts the application of immunotherapy. Here, we construct a tumor protein-engineering system based on the functional tripeptide, Asp-Phe-Tyr (DFY), which can automatically collect and deliver immunogenetic tumor proteins from targeted cells to immune cells. Through a tyrosinase-catalyzed polymerization, the DFY tripeptide selectively accumulates in tyrosinase high-expressed melanoma cells. Then quinone-rich intermediates are covalently linked with tumor-specific proteins by Michael addition and form tumor protein-carried microfibers that could be engulfed by antigen-presenting cells and exhibited tumor antigenic properties for boosting immune effect. In melanoma cells with deficient antigen presentation, this system can successfully enrich and transport tumor antigen-containing proteins to immune cells. Furthermore, in the in vivo study on murine melanoma, the transdermal delivery of the DFY tripeptide suppressed the tumor growth and the postsurgery recurrence. Our findings provide an avenue for the regulation of the immune system on an organism by taking advantage of certain polymerization reactions by virtue of chemical biology.
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Inmunoterapia/métodos , Melanoma Experimental/terapia , Monofenol Monooxigenasa/metabolismo , Oligopéptidos/uso terapéutico , Administración Cutánea , Animales , Células Presentadoras de Antígenos/inmunología , Catálisis , Melanoma Experimental/inmunología , Ratones , Oligopéptidos/administración & dosificación , Oligopéptidos/metabolismo , PolimerizacionRESUMEN
BACKGROUND: Angiogenesis, the formation of blood vessel from pre-existing ones, plays an important role in many pathophysiological diseases, such as cancer. Opioids are often used in clinic for the management of chronic pain in cancer patients at terminal phases. Here, we investigated and compared the effects and mechanisms of four opioids on angiogenesis. METHODS: We performed angiogenesis assays on human umbilical vein endothelial cells (HUVEC) that represent an in vitro model to assess the toxicity of drugs to endothelium. RESULTS: Morphine and oxycodone at 0.1 µM to 100 µM dose-dependently increased endothelial cell tube formation and proliferation. We observed the same in endothelial cells exposed to fentanyl at 0.1 µM to 10 µM but there was a gradual loss of stimulation by fentanyl at 100 µM and 1000 µM. Morphine and fentanyl reduced endothelial cell apoptosis-induced by serum withdrawal whereas oxycodone did not display anti-apoptotic effect, via decreasing Bax level. Oxycodone at the same concentrations was less potent than morphine and fentanyl. Different from other three opioids, codeine at all tested concentrations did not affect endothelial cell tube formation, proliferation and survival. Mechanism studies demonstrated that opioids acted on endothelial cells via µ-opioid receptor-independent pathway. Although we observed the increased phosphorylation of mitogen-activated protein kinase (MAPK) in cells exposed to morphine, fentanyl and oxycodone, the rescue studies demonstrated that the stimulatory effects of morphine but not fentanyl nor oxycodone were reversed by a specific MAPK inhibitor. CONCLUSION: Our work demonstrates the differential effects and mechanisms of opioids on angiogenesis.
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Analgésicos Opioides/farmacología , Células Endoteliales/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fentanilo/farmacología , Humanos , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Morfina/farmacología , Oxicodona/farmacología , Fosforilación , Venas Umbilicales/citologíaRESUMEN
To improve the efficiency of the Fe(II)/Fe(III) cycle and continuous reactivity of pyrite, a pyrite/H2O2/hydroxylamine (HA) system was proposed to treat rhodamine B (RhB). The results showed that near-complete decolorization and 52.8% mineralization 50 mg L-1 RhB were achieved under its optimum conditions: HA 0.8 mM, H2O2 1.6 mM, pyrite 0.4 g L-1, and initial pH 4.0. The degradation reaction was dominated by an â¢OH radical produced by the reaction of Fe2+ with H2O2 in solution. HA primarily had two roles: in solution, HA could accelerate the Fe(II)/Fe(III) cycle through its strong reducibility to enhance RhB decolorization; on the pyrite surface, HA could improve the continuous reactivity of pyrite by inhibiting the oxidation of pyrite. In addition, the dosing manner of HA had a significant effect on RhB decolorization. In addition, the high decolorization and mineralization efficiency of other dye pollutants suggested that the pyrite/H2O2/HA system might be widely used in textile wastewater treatment.
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Peróxido de Hidrógeno , Contaminantes Químicos del Agua , Compuestos Férricos , Hidroxilamina , Hidroxilaminas , Hierro , Oxidación-Reducción , Rodaminas , Sulfuros , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVE: Post-operative concurrent chemoradiotherapy has become the standard treatment for patients with positive lymph nodes after radical surgery. The aim of this study was to explore the efficiency and safety of consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy. METHOD: We reviewed the medical records of patients with early-stage cervical cancer with lymph node metastasis after radical hysterectomy from January 2010 to January 2017. All patients underwent adjuvant concurrent chemoradiotherapy (n=49) or three cycles of platinum-based consolidation chemotherapy following concurrent chemoradiotherapy (n=89). The primary end points of the study were disease-free survival and overall survival. RESULTS: The median follow-up time was 51 months (range 10-109). No significant difference was noted in disease-free survival, overall survival, or grade 3/4 gastrointestinal disorder between the consolidation chemotherapy group (78.1% vs 83.1% vs 6.7%) and the concurrent chemoradiotherapy alone group (75.4% vs 75.3% vs 4.1%), (p=0.42, 0.26, 0.80, respectively). However, the grade 3/4 myelosuppression rate in the consolidation group was higher than in the concurrent chemoradiotherapy alone group (40.4% vs 22.4%, p=0.03). For patients with >3 positive lymph nodes or patients with >2 positive lymph nodes+lymphovascular space invasion/≥1/3 stromal invasion, disease-free survival and overall survival were superior in the consolidation chemotherapy group compared with the concurrent chemoradiotherapy alone group (p<0.05). CONCLUSION: In patients with >3 positive lymph nodes or patients with >2 positive lymph nodes, lymphovascular space invasion, and greater than 1/3 stromal invasion, disease-free survival and overall survival were superior with consolidation chemotherapy. However, consolidation chemotherapy was also associated with an increased grade 3/4 myelosuppression rate.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ganglios Linfáticos/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/cirugía , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Quimioterapia de Consolidación , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Femenino , Humanos , Histerectomía , Liposomas/administración & dosificación , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
Oxidative stress, inflammation, and hypertension constitute a self-perpetuating vicious circle to exacerbate hypertension and subsequent hypertensive cardiac hypertrophy. NADPH oxidase (Nox) 1/4 inhibitor GKT137831 alleviates hypertensive cardiac hypertrophy in models of secondary hypertension; however, it remains unclear about its effect on hypertensive cardiac hypertrophy in models of essential hypertension. This study is aimed at determining the beneficial role of GKT137831 in hypertensive cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and its mechanisms of action. Treating with GKT137831 prevented cardiac hypertrophy in SHRs. Likewise, decreasing production of reactive oxygen species (ROS) with GKT137831 reduced epidermal growth factor receptor (EGFR) activity in the left ventricle of SHRs. Additionally, EGFR inhibition also reduced ROS production in the left ventricle and blunted hypertensive cardiac hypertrophy in SHRs. Moreover, inhibition of the ROS-EGFR pathway with Nox1/4 inhibitor GKT137831 or selective EGFR inhibitor AG1478 reduced protein and mRNA levels of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß), as well as the activities of Akt and extracellular signal-regulated kinase (ERK) 1/2 in the left ventricle of SHRs. In summary, GKT137831 prevents hypertensive cardiac hypertrophy in SHRs, Nox-deprived ROS regulated EGFR activation through positive feedback in the hypertrophic myocardium, and inhibition of the ROS-EGFR pathway mediates the protective role of GKT137831 in hypertensive cardiac hypertrophy via repressing cardiac inflammation and activation of Akt and ERK1/2. This research will provide additional details for GKT137831 to prevent hypertensive cardiac hypertrophy.
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Cardiomegalia/tratamiento farmacológico , Cardiomegalia/metabolismo , Inflamación/tratamiento farmacológico , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirazolonas/uso terapéutico , Piridonas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Western Blotting , Ecocardiografía , Ensayo de Inmunoadsorción Enzimática , Hemodinámica/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Inmunohistoquímica , Inflamación/metabolismo , Masculino , Malondialdehído/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Rutaecarpine attenuates hypertensive cardiac hypertrophy in the rats with abdominal artery constriction (AAC); however, its mechanism of action remains largely unknown. Our previous study indicated that NADPH oxidase 4 (Nox4) promotes angiotensin II (Ang II)-induced cardiac hypertrophy through the pathway between reactive oxygen species (ROS) and a disintegrin and metalloproteinase-17 (ADAM17) in primary cardiomyocytes. This research aimed to determine whether the Nox4-ROS-ADAM17 pathway is involved in the protective action of rutaecarpine against hypertensive cardiac hypertrophy. AAC-induced hypertensive rats were adopted to evaluate the role of rutaecarpine in hypertensive cardiac hypertrophy. Western blotting and real-time PCR were used to detect gene expression. Rutaecarpine inhibited hypertensive cardiac hypertrophy in AAC-induced hypertensive rats. These findings were confirmed by the results of in vitro experiments that rutaecarpine significantly inhibited Ang II-induced cardiac hypertrophy in primary cardiomyocytes. Likewise, rutaecarpine significantly suppressed the Nox4-ROS-ADAM17 pathway and over-activation of extracellular signal-regulated kinase (ERK) 1/2 pathway in the left ventricle of AAC-induced hypertensive rats and primary cardiomyocytes stimulated with Ang II. The inhibition of Nox4-ROS-ADAM17 pathway and over-activation of ERK1/2 might be associated with the beneficial role of rutaecarpine in hypertensive cardiac hypertrophy, thus providing additional evidence for preventing hypertensive cardiac hypertrophy with rutaecarpine.
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Proteína ADAM17/genética , Cardiomegalia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Alcaloides Indólicos/farmacología , NADPH Oxidasa 4/genética , Quinazolinas/farmacología , Angiotensina II/genética , Animales , Aorta Abdominal/patología , Cardiomegalia/etiología , Constricción Patológica/complicaciones , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipertensión/etiología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Ratas , Ratas Endogámicas Dahl , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The biological effects of sevoflurane, a volatile anesthetics, on cancer cells seem to be contradictory and are not fully understood. While some studies demonstrate that sevoflurane promotes tumor growth, other studies report that sevoflurane displays anti-cancer activities. In this work, we systematically investigated the effects of sevoflurane at clinically relevant dose on the multiple biological aspects of cervical cancer cells and analyzed the underlying mechanism. Using a panel of cell lines, we found that sevoflurane significantly inhibited proliferation and migration of cervical cancer cells regardless of cellular origin and genetic background. In contrast, sevoflurane did not affect cervical cancer survival. Additionally, sevoflurane significantly enhanced chemosensitivity of cervical cancer cells. Mechanistically, we show that sevoflurane inhibits Ras and RhoA GTPase activities, leading to the blockade of their downstream signaling pathways, such as Ras/Erk/Akt and Rho/MYPT1/MLC. The rescue studies using Rho activator calpeptin or constitutively active Ras further confirm that Ras and RhoA are the targets of sevoflurane in cervical cancer. Interestingly, we found that the anti-proliferative effect of sevoflurane was via targeting Ras whereas the anti-migratory effect of sevoflurane was mediated via targeting RhoA. Our data clearly demonstrates the anti-cancer effects of sevoflurane. These findings provide preclinical evidence into the potential mechanisms by which sevoflurane may negatively affect cervical cancer growth and metastasis.
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Antineoplásicos/farmacología , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Sevoflurano/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células HeLa , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
INTRODUCTION: Impaired mitochondrial function is a key factor attributing to the lung ischemia reperfusion injury (LIRI). Methylene blue (MB) has been reported to attenuate brain and renal ischemia-reperfusion injury. We hypothesized that MB also could have a protective effect against LIRI by preventing mitochondrial oxidative damage. METHODS: Isolated rat lungs were assigned to the following four groups (n = 6): a sham group: perfusion for 105 min without ischemia; I/R group: shutoff of perfusion and ventilation for 45 min followed by reperfusion for 60 min; and I/R + MB group and I/R + glutathione (GSH) group: 2 mg/kg MB or 4 µM glutathione were intraperitoneally administered for 2 h, and followed by 45 min of ischemia and 60 min of reperfusion. RESULTS: MB lessened pulmonary dysfunction and severe histological injury induced by ischemia-reperfusion injury. MB reduced the production of reactive oxygen species and malondialdehyde and enhanced the activity of superoxide dismutase. MB also suppressed the opening of the mitochondrial permeability transition pore and partly preserved mitochondrial membrane potential. Moreover, MB inhibited the release of cytochrome c from the mitochondria into the cytosol and decreased apoptosis. Additionally, MB downregulated the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-18). CONCLUSION: MB protects the isolated rat lungs against ischemia-reperfusion injury by attenuating mitochondrial damage.
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Inhibidores Enzimáticos/farmacología , Azul de Metileno/farmacología , Mitocondrias/fisiología , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Apoptosis/efectos de los fármacos , Transporte Biológico/efectos de los fármacos , Citocromos c/metabolismo , Citocinas/genética , Pulmón/patología , Pulmón/fisiopatología , Masculino , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Poro de Transición de la Permeabilidad Mitocondrial , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Superóxido Dismutasa , Transcripción Genética/efectos de los fármacosRESUMEN
Calcitonin gene-related peptide (CGRP) has a potent protective action on the cardiovascular system; however, little is known about the role of CGRP in angiotensin II- (Ang II-) induced inflammation of vascular smooth muscle cells (VSMCs). This study is aimed at determining the anti-inflammatory effect of CGRP in Ang II-treated VSMCs and whether a disintegrin and metalloproteinase 17 (ADAM17) modulates this protective action. Small interference RNA (siRNA) and inhibitors of CGRP, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase 1/2 (ERK1/2) were adopted to investigate their effect on Ang II-induced inflammation in VSMCs. Here, we found that CGRP could inhibit inflammation and decrease ADAM17 expression and activation of EGFR and ERK1/2 in VSMCs stimulated with Ang II. Results of siRNA demonstrated that ADAM17 siRNA attenuated Ang II-induced inflammation and up-regulation of activities of EGFR and ERK1/2 in VSMCs. Furthermore, the EGFR-ERK1/2 pathway promoted Ang II-induced VSMC inflammation. In summary, these findings identify the anti-inflammatory effect of CGRP in VSMCs stimulated by Ang II and suggest that ADAM17 is involved in the protective effect of CGRP against Ang II-induced inflammation via the EGFR-ERK1/2 pathway in VSMCs.
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Proteína ADAM17/metabolismo , Angiotensina II/efectos adversos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Inflamación/metabolismo , Miocitos del Músculo Liso/metabolismo , Animales , Línea Celular , Receptores ErbB/metabolismo , Inflamación/inducido químicamente , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Músculo Liso Vascular/citología , ARN Interferente Pequeño/metabolismo , Ratas , Sistema Renina-AngiotensinaRESUMEN
An efficient solvent-free protocol for the Buchwald-Hartwig cross-coupling reaction of aryl and heteroaryl chlorides with primary and secondary amines using the Pd(dba)2/ligand 1 catalytic system has been developed. Notably, the catalytic system also efficiently catalyzed the reaction under aqueous conditions.
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An easily available Pd(OAc)2/(2-(anthracen-9-yl)-1H-inden-3-yl) dicyclohexylphosphine/toluene/iPrOH/water catalytic system was developed, which shows high catalytic activity in the Suzuki-Miyaura cross-coupling reactions of a diverse array of aryl and heteroaryl chlorides with Pd loadings down to 0.01 mol%.
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OBJECTIVE: We investigated the effects of fluoxetine on the short-term and long-term neural functional prognoses after ischemic stroke. METHODS: In this prospective randomized controlled single-blind clinical study in China, eligible patients afflicted with ischemic stroke were randomized into control and treatment groups. Patients in the treatment group received fluoxetine in addition to the basic therapies in the control group over a period of 90 days. The follow-up period was 180 days. We evaluated the effects of fluoxetine on the National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score after ischemic stroke through single- and multiple-factor analysis. RESULTS: The mean NIHSS score on day 180 after treatment was significantly lower in the treatment group than in the control group (P = .009). The mean BI scores on days 90 and 180 were significantly higher in the treatment group (P = .026) than in the control group (P = .011). The improvements in the NIHSS and BI scores on days 90 and 180 compared with baseline in the treatment group were all significantly greater than that in the control group (P = .033, P = .013, P = .013, P = .019, respectively). Treatment with fluoxetine was an independent factor affecting the NIHSS and BI scores on day 180 after treatment. CONCLUSION: Treatment with fluoxetine for 90 days after ischemic stroke can improve the long-term neural functional outcomes.
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Fluoxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , Isquemia Encefálica/complicaciones , China , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Índice de Severidad de la Enfermedad , Método Simple Ciego , Accidente Cerebrovascular/etiología , Factores de TiempoRESUMEN
We theoretically study high-order harmonic generation (HHG) and attosecond pulses from an atom irradiated synchronically by a terahertz (THz) pulse and an infrared laser pulse. For the HHG spectrum from the THz pulse alone and the combined pulse, an apparent peak-valley structure appears the platform region. Specially, for the periodic structure generated by an atom under the action of the combined pulse is originated from the interference between the electrons ionized at different instants in the laser field, which undergo many recollision and return to the core at the same time. Therefore, continuum harmonics with few chirps from the interference enhancement region can be achieved, which result in a chirp-free isolated attosecond pulse.