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This study examined the spatial and monthly variations in reproductive dynamics of Pacific saury collected in the high sea (40°N-49°N, 149°E-168°E) of the northwestern Pacific during the fishing season of the Taiwanese stick-held dip-net fisheries (July-November) from 2018 to 2019. Generalized additive mixed-effects models (GAMMs) were applied to explore the relationship between the probability of maturing and spawning occurrence (PMOS ) and the explanatory variables (month, body length, sea-surface temperature [SST] as fixed effects, and fishing set as a random effect) for the age 0 and age 1 fish, respectively. In addition, the impact of the geographical difference in growth rates of age 0 fish, quantified as the radius of the otolith annual ring, on the PMOS of age 1 fish was explored in the GAMMs. Results showed that the mean values of the condition factor (CF) varied by months, and higher mean CFs were observed north of 45°N. However, the mean values of the gonado-somatic index did not show a clear spatiotemporal pattern. The spatial distribution of the ovarian maturation states revealed that the spawning ground of Pacific saury during July-November was broader than that previously known and had partly overlapped with the high-sea fishing ground. The best GAMM showed that the predicted PMOS of the age 0 fish were generally low (mean = 19%, standard deviation [SD] = 10%) and tended to increase with increasing body length. In contrast, the predicted PMOS were relatively higher (mean = 37%, SD = 10%) for the age 1 fish and increased with increasing SST and decreasing latitude. Two candidate GAMMs, which are equally supported as the best model (ΔAIC < 2), provide evidence that a higher growth rate of age 0 fish may result in higher reproductive activity in age 1 fish. This is one of few studies focusing on the reproductive dynamics of Pacific saury during the fishing season; current limitations, future directions, and conservation implications were discussed.
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Explotaciones Pesqueras , Peces , Reproducción , Animales , Estaciones del Año , Análisis Espacio-TemporalRESUMEN
AIMS: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. METHODS: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re-grade ESCCs. RESULTS: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression-free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4-tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. CONCLUSIONS: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Supervivencia sin Enfermedad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Clasificación del Tumor , Pronóstico , Estudios RetrospectivosRESUMEN
The selective N-alkylation of indole substrates remains an ongoing research challenge for the relative attenuated nucleophilicity toward nitrogen. Herein, we developed the hydroxymethylation of indole derivatives to afford N-alkylated indole products with formic acid. This metal-free process was promoted by the organic base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) using phenylsilane as the reductant under mild conditions. Besides, this strategy represents an alternative way for indirect utilization of CO2, considering the facile hydrogenation of CO2 to produce HCOOH.
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Dióxido de Carbono , Formiatos , Catálisis , Indoles , MetalesRESUMEN
Ocean warming induced by climate change is the greatest threat to the persistence of coral reefs globally. Given the current rate of ocean warming, there may not be sufficient time for natural acclimation or adaptation by corals. This urgency has led to the exploration of active management techniques aimed at enhancing thermal tolerance in corals. Here, we test the capacity for transgenerational acclimation in the reef-building coral Pocillopora acuta as a means of increasing offspring performance in warmer waters. We exposed coral colonies from a reef influenced by intermittent upwelling and constant warm-water effluent from a nuclear power plant to temperatures that matched (26 °C) or exceeded (29.5 °C) season-specific mean temperatures for three reproductive cycles; offspring were allowed to settle and grow at both temperatures. Heated colonies reproduced significantly earlier in the lunar cycle and produced fewer and smaller planulae. Recruitment was lower at the heated recruitment temperature regardless of parent treatment. Recruit survival did not differ based on parent or recruitment temperature. Recruits from heated parents were smaller and had lower maximum quantum yield (Fv/Fm), a measurement of symbiont photochemical performance. We found no direct evidence that thermal conditioning of adult P. acuta corals improves offspring performance in warmer water; however, chronic exposure of parent colonies to warmer temperatures at the source reef site may have limited transgenerational acclimation capacity. The extent to which coral response to this active management approach might vary across species and sites remains unclear and merits further investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00338-021-02123-9.
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Compounds bearing organophosphorus motifs and 2-oxazolidinone have found numerous applications in pharmaceutical chemistry, homogeneous catalysis, and organic materials. Here, we describe an efficient and selective protocol for straightforward access to a series of 5-((diarylphosphoryl)methyl)oxazolidin-2-ones via the copper-catalyzed difunctionalization of the C≡C bond of propargylic amines with CO2 and phosphine oxide. Notably, copper catalysis is a sustainable and benign catalytic mode. This reaction proceeds under mild reaction conditions, which is operationally simple and scalable with a broad scope, exclusive selectivity, and good functional group compatibility. Mechanistic studies suggest a one-pot tandem cyclization/radical addition sequence, along with the phosphorylation/cyclization scheme.
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Anetodermia/diagnóstico por imagen , Enfermedades del Cabello/diagnóstico por imagen , Pilomatrixoma/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Adolescente , Anetodermia/complicaciones , Anetodermia/patología , Dermoscopía , Enfermedades del Cabello/patología , Humanos , Inmunohistoquímica , Masculino , Pilomatrixoma/complicaciones , Pilomatrixoma/patología , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: This study aims to evaluate concentrations of pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF)-A in aqueous of patients with neovascular glaucoma prior to, and shortly after, an intravitreal ranibizumab injection. DESIGN: Interventional comparative study. PARTICIPANTS: The study included patients undergoing an intravitreal ranibizumab injection about one week before anti-glaucomatous surgery (study group) or who underwent routine cataract surgery (control group). METHODS: Aqueous and blood samples were collected at the occasions of intravitreal injections, anti-glaucomatous surgery or cataract surgery. They were analysed by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Concentrations of PEDF and VEGF-A in aqueous. RESULTS: At baseline, concentrations VEGF-A (3698 ± 2105 pg/mL vs. 233 ± 98 pg/mL) and PEDF (18.9 ± 11.9 ug/mL vs. 2.2 ± 0.6 ug/mL) were higher (P < 0.001) in the study group (n = 20 patients) than control group (n = 20 patients). The VEGF-A/PEDF concentration ratio was higher in the study group (396 ± 554 vs. 110 ± 49; P = 0.02). One week after the ranibizumab injection, iris neovascularization had completely regressed in 17 (85%) eyes, and VEGF-A concentration decreased significantly (P < 0.001) to 184 ± 130 pg/mL. The PEDF concentration remained unchanged (19 ± 12 ug/mL). The VEGF-A/PEDF concentration ratio decreased to 13.2 ± 13.6. Plasma concentrations of VEGF-A and PEDF did not differ significantly between both groups (P = 0.65 and P = 0.15, respectively) nor were they significantly correlated with the aqueous concentrations (all P > 0.15). CONCLUSIONS: Aqueous concentrations of VEGF-A and PEDF were significantly elevated in eyes with neovascular glaucoma. Within one week after intravitreal injection of ranibizumab, VEGF-A concentration decreased to subnormal levels, while the PEDF concentration remained unchanged and the VEGF-A/PEDF ratio decreased.
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Inhibidores de la Angiogénesis/uso terapéutico , Humor Acuoso/metabolismo , Proteínas del Ojo/metabolismo , Glaucoma Neovascular/tratamiento farmacológico , Factores de Crecimiento Nervioso/metabolismo , Ranibizumab/uso terapéutico , Serpinas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Angiografía con Fluoresceína , Glaucoma Neovascular/metabolismo , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza VisualRESUMEN
The increasing presence of aquatic contaminants, such as the pharmaceutical fluoxetine, has raised concerns over potentially disrupting effects on several aspects of fish reproduction. However, the effects of fluoxetine on reproductive and paternal behavior in fish remain understudied, particularly at environmentally relevant concentrations. In the current study, we therefore tested the hypothesis that waterborne fluoxetine at an environmentally relevant concentration (540 ng/l), disrupts specific reproductive and paternal behaviors in male Siamese fighting fish at distinct reproductive phases. A pre-post test design was adopted to investigate specific behavioral responses at the individual fish level in response to male conspecific intruders at two different distances from the nest across four distinct reproductive phases (before bubblenest construction, following bubblenest construction, after spawning and after hatching of the larvae). In the control specimens, the measured behaviours were not different between the spawning times and among the interactions in either distance to nest at the different reproduction phases. Our results indicate that fluoxetine specifically disrupts characteristic paternal territorial aggression behaviour only after spawning and hatching of the larvae, while male behaviour in previous reproductive phases is unaffected by fluoxetine exposure. Results of comparison between males at 1st spawning and specimens exposed to fluoxetine at 2nd spawning showed that the first reaction of the nest-holding males to the intruders, duration of fin spreading, number of bites, and 90° turn, and the frequency of sweeps were different between the spawning times after spawning or hatching of embryos. However, interaction of spawning time and reproduction phase was significant on biting behaviour. These results demonstrate that fluoxetine exposure at environmental concentrations negatively affects territorial defense behaviour in fighting fish during parental care after larval hatching, which may have possible implications on reproductive success and population dynamics.
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Agresión/efectos de los fármacos , Fluoxetina/toxicidad , Perciformes/fisiología , Conducta Sexual Animal/efectos de los fármacos , Territorialidad , Animales , MasculinoRESUMEN
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Over the past two decades, numerous researchers have provided important evidence regarding the role of tight junction (TJ) proteins in the occurrence and progression of CRC. The causal relationship between the presence of specific TJ proteins and the development of CRC has also been confirmed. Despite the large number of publications in this field, a bibliometric study to review the current state of research and highlight the research trends and hotspots in this field has not yet been performed. AIM: To analyze research on TJs and CRC, summarize the field's history and current status, and predict future research directions. METHODS: We searched the Science Citation Index Expanded database for all literature on CRC and TJs from 2001-2023. We used bibliometrics to analyze the data of these papers, such as the authors, countries, institutions, and references. Co-authorship, co-citation, and co-occurrence analyses were the main methods of analysis. CiteSpace and VOSviewer were used to visualize the results. RESULTS: A total of 205 studies were ultimately identified. The number of publications on this topic has steadily increased since 2007. China and the United States have made the largest contributions to this field. Anticancer Research was the most prolific journal, publishing 8 articles, while the journal Oncogene had the highest average citation rate (68.33). Professor Dhawan P was the most prolific and cited author in this field. Co-occurrence analysis of keywords revealed that "tight junction protein expression", "colorectal cancer", "intestinal microbiota", and "inflammatory bowel disease" had the highest frequency of occurrence, revealing the research hotspots and trends in this field. CONCLUSION: This bibliometric analysis evaluated the scope and trends of TJ proteins in CRC, providing valuable research perspectives and future directions for studying the connection between the two. It is recommended to focus on emerging research hotspots, such as the correlations among intestinal microbiota, inflammatory bowel disease, TJ protein expression, and CRC.
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Potent P2Y12 receptor antagonists have been used widely for patients undergoing percutaneous coronary intervention with different results. Benefits from different regimens various between trials. Randomized controlled trials (RCTs) have restrictive inclusion and exclusion criteria; thus, they may limit the generalizability of the findings to a broader population. This study was aimed to comprehensively investigate the outcomes of potent P2Y12 inhibitors in patients undergoing PCI, including RCTs and real-world evidence (RWE) studies. Multiple electronic databases were systemically reviewed and searched on compared potent P2Y12 inhibitors with clopidogrel. The primary efficacy end point was composite ischemic cardiovascular event and primary safety endpoint was major bleeding. Overall estimates of proportions and incidence rates with 95 % confidence intervals (CI) were calculated using fixed-effects models. Total 24 studies (140,986 patients) underwent coronary intervention were included in this meta-analysis, including 18 RCTs and 6 large cohort studies with propensity score matching. The potent P2Y12 inhibitors including cangrelor, prasugrel, and ticagrelor, significantly decreased the risk of composite adverse cardiovascular ischemic events (95 % CI 0.89-0.96, p < 0.001), but increased major bleeding (95 % CI 1.15-1.33, p < 0.001) or any bleeding (95 % CI 1.21-1.33, p < 0.001) compared with Clopidogrel. This meta-analysis merges RCTs and RWE studies and comprehensively evidences newer potent P2Y12 inhibitors are significantly more effective than clopidogrel in reduction of composite adverse thrombotic events, but the incidence of major or any bleeding was higher compared with clopidogrel.
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Geographical background and dispersal ability may strongly influence assemblage dissimilarity; however, these aspects have generally been overlooked in previous large-scale beta diversity studies. Here, we examined whether the patterns and drivers of taxonomic beta diversity (TBD) and phylogenetic beta diversity (PBD) of breeding birds in China vary across (1) regions on both sides of the Hu Line, which demarcates China's topographical, climatic, economic, and social patterns, and (2) species with different dispersal ability. TBD and PBD were calculated and partitioned into turnover and nestedness components using a moving window approach. Variables representing climate, habitat heterogeneity, and habitat quality were employed to evaluate the effects of environmental filtering. Spatial distance was considered to assess the impact of dispersal limitation. Variance partitioning analysis was applied to assess the relative roles of these variables. In general, the values of TBD and PBD were high in mountainous areas and were largely determined by environmental filtering. However, different dominant environmental filters on either side of the Hu Line led to divergent beta diversity patterns. Specifically, climate-driven species turnover and habitat heterogeneity-related species nestedness dominated the regions east and west of the line, respectively. Additionally, bird species with stronger dispersal ability were more susceptible to environmental filtering, resulting in more homogeneous assemblages. Our results indicated that regions with distinctive geographical backgrounds may present different ecological factors that lead to divergent assemblage dissimilarity patterns, and dispersal ability determines the response of assemblages to these ecological factors. Identifying a single universal explanation for the observed pattern without considering these aspects may lead to simplistic or incomplete conclusions. Consequently, a comprehensive understanding of large-scale beta diversity patterns and effective planning of conservation strategies necessitate the consideration of both geographical background and species dispersal ability.
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Biodiversidad , Ecosistema , Animales , Filogenia , China , Aves/genéticaRESUMEN
OBJECTIVE: To survey the distribution pattern and subject domain knowledge of worldwide glaucoma research based on literatures in Pubmed database. METHODS: Literatures on glaucoma published in 2007 to 2011 were identified in Pubmed database. The analytic items of an article include published year, country, language author, and journal. After core mesh terms had been characterized by BICOMS, the co-occurrence matrix was built. Cluster analysis was finished by SPSS 20.0. Then visualized network was drawn using ucinet 6.0. RESULTS: Totally 6427 literatures were included, the number of annual articles changed slightly between 2007 and 2011. The United States, England, Germany, Australia, and France together accounted for 77.63% of articles. There were 52 high-frequency subjects and hot topics were clustered into the following 10 categories: (1) Pathology of optic disc and nerve fibers and OCT application, (2) METHODS: of visual field (VF) and visual function examination, (3) Glaucoma drug medications, (4) Pathology and physiology of primary open angle glaucoma (POAG) including VF and intraocular pressure (IOP), (5) Glaucoma surgery, (6) Gene research related to POAG, (7) Glaucoma disease pathology and animal models, (8) Ocular hypertension (OHT) induced complications and corneal changes, (9) Etiology of congenital glaucoma and complications, (10) Etiology and epidemiology of glaucoma. The visualized domain knowledge mapping was successfully built. The pathology of optic disc and nerve fibers, medications, and surgery were well developed. Study on IOP and visual field was in the core domain, which have an important link to etiology, diagnosis, and therapy. The researches on glaucomatous gene, disease pathology model, congenital glaucoma, etiology and epidemiology were not developed well, which are of great promotion space. CONCLUSIONS: The distribution pattern and subject domain knowledge of worldwide glaucoma research in the recent five years were shown by using bibliometric analysis.Western developed countries play a leading role in the field of glaucoma research, the international influence of related research in China needs to be strengthened.
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Bibliometría , Glaucoma , PubMed , Análisis por Conglomerados , HumanosRESUMEN
Ocean warming and marine heatwaves induced by climate change are impacting coral reefs globally, leading to coral bleaching and mortality. Yet, coral resistance and resilience to warming are not uniform across reef sites and corals can show inter- and intraspecific variability. To understand changes in coral health and to elucidate mechanisms of coral thermal tolerance, baseline data on the dynamics of coral holobiont performance under non-stressed conditions are needed. We monitored the seasonal dynamics of algal symbionts (family Symbiodiniaceae) hosted by corals from a chronically warmed and thermally variable reef compared to a thermally stable reef in southern Taiwan over 15 months. We assessed the genera and photochemical efficiency of Symbiodiniaceae in three coral species: Acropora nana, Pocillopora acuta, and Porites lutea. Both Durusdinium and Cladocopium were present in all coral species at both reef sites across all seasons, but general trends in their detection (based on qPCR cycle) varied between sites and among species. Photochemical efficiency (i.e., maximum quantum yield; Fv/Fm) was relatively similar between reef sites but differed consistently among species; no clear evidence of seasonal trends in Fv/Fm was found. Quantifying natural Symbiodiniaceae dynamics can help facilitate a more comprehensive interpretation of thermal tolerance response as well as plasticity potential of the coral holobiont.
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Antozoos , Dinoflagelados , Animales , Antozoos/fisiología , Arrecifes de Coral , Blanqueamiento de los Corales , Cambio ClimáticoRESUMEN
OBJECTIVE: To analyze the stroma changes of benign and malignant human prostate tissues. METHODS: For the identification of stroma cells phenotype in human prostate cancer and benign prostate hyperplasia tissues, Masson method and immunohistochemical analysis of α-smooth muscle actin (α-SMA), desmin, and vimentin were performed. The relative volume of intratumor stroma (0%, Grade 0; 1% - 33%, Grade 1; 34% - 66%, Grade 2; 67% - 100%, Grade 3) were quantified and analyzed in local and advanced prostate cancer tissues. RESULTS: Stroma myofibroblasts in prostate cancer were stained green by Masson staining and showed a co-expression of α-SMA and vimentin without an expression of desmin. It was significantly different from smooth muscle cells in benign prostate hyperplasia stained red and co-expressing a-SMA and desmin. Statistical analysis showed that high stroma volume (Grade 2/3) in advanced prostate cancer were significantly higher than that in an early stage of prostate cancer (83% vs 55%, P < 0.05). CONCLUSION: Significant phenotypic differences of stroma cells existed in benign and malignant human prostate tissues. A high expression of myofibroblasts in advanced prostate cancer may play an important role in cancer progression. And its clinical significance should raise a high alert.
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Próstata/patología , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Células del Estroma/patología , Actinas/metabolismo , Anciano , Anciano de 80 o más Años , Desmina/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Próstata/citología , Células del Estroma/metabolismo , Vimentina/metabolismoRESUMEN
OBJECTIVE: To investigate the serum levels of sCD44v6 and sE-cadherin (sE-cad) in patients with esophageal squamous cell carcinoma. METHODS: The serum samples were collected from 65 cases of esophageal squamous cell carcinoma, 32 cases of erosive esophagitis and 35 healthy subjects. Serum sCD44v6 and sE-cad levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: The mean levels of serum sCD44v6 and sE-cad in esophageal squamous cell carcinoma patients were significantly higher than those of erosive esophagitis patients and normal controls (both P<0.05). There was no significant difference in serum sCD44v6 and sE-cad levels between erosive esophagitis patients normal controls (P=0.566 and P=0.708, respectively). Serum sCD44v6 and sE-cad levels of esophageal cancer patients were not correlated with their clinicopathological features. Serum sCD44v6 level is not correlated with sE-cad level in squamous cell carcinoma patients(P=0.651). CONCLUSION: Serum sCD44v6 and sE-cad might be a potential marker for screening of esophageal squamous cell carcinoma.
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Cadherinas/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Esofágicas/sangre , Receptores de Hialuranos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A palladium-catalyzed four-component carboxylative cyclization comprising propargylic amines, aryl iodides, CO2 and CO was developed. By selecting Et3N and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the base, respectively, both terminal and internal propargylic amines proceeded well facilitated by Pd(PPh3)2Cl2, affording the functionalized 2-oxazolones in moderate yields. This protocol enlarges the product diversity based on CO2 conversion and simultaneously provides a cooperative transformation route for both CO2 and CO.
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Background: Cutaneous squamous cell carcinoma (cSCC), a kind of skin cancer with high rates of morbidity and mortality, occurs frequently in the clinic. Although early surgical treatment can achieve good results, there is no effective prevention and treatment for the recurrence and metastasis of cSCC. As a useful resource to protect humans from disease, traditional Chinese medicine (TCM) has been adopted by clinicians for thousands of years. Methods: In this study, we collected a Chinese medicine formula and then employed a data mining method to analyze drug combinations of Si-Jun-Zi (SJZ) decoction. Multiple databases were used in this study to predict various ingredients, compounds, and their targets in the decoction. The potential targets of cSCC were also obtained from the database in the same way. In addition, as bioinformatics analysis methods, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used in our research as supplementary means to network pharmacology. Finally, we used ultra-performance liquid chromatography (UPLC) fingerprinting to analyze the effective components of the TCM decoction. Results: We detected 559 active compounds from Ginseng, Largehead Atractylodes, India Bread, and Glycyrrhiza Inflata, and selected 136 molecules under specific conditions. The mechanisms of the TCM formula were illustrated by the network pharmacology, such as compounds-herb network, compounds-target network, disease-target network, and target-target interaction network, as well as characteristics of the TCM. Then, GO analysis and KEGG analysis were performed on the compounds in the network using multiple methods of data mining and bioinformatics, and 10 candidate targets were identified. In addition, the UPLC fingerprinting method was used to analyze the components of SJZ decoction. Conclusions: Network pharmacology was performed to investigate the characteristics and mechanism of SJZ decoction, and a bioinformatics method was used to analyze the relationship between the effective compounds of the SJZ TCM decoction and cSCC-related specific targets and pathways, to find a variety of candidate compounds with multi-target activity.
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OBJECTIVE: To study the effect of sodium cantharidinate on the angiogenesis of nude mice with human gastric cancer. METHODS: Nude mice xenograft models of human gastric cancer were established by injecting gastric carcinoma cell BGC823 into peritoneal. Expression of VEGF and MVD labeling by CD34 in human gastric cancer cells were measured by immunohistochemistry. RESULTS: Expression scores of VEGF in medium dose and high dose group with sodium cantharidinate treatment were lower than those in low dose and control group (P < 0.01). There was no significant difference between medium dose and high dose group or low dose and control group (P > 0.05). MVD values in medium and high dose group with sodium cantharidinate treatment were lower than those in low dose and control group (P < 0.01), but there was no significant difference between medium dose and high dose group (P > 0.05). CONCLUSIONS: sodium cantharidinate can inhibit the growth of the tumor by down-regulating VEGF expression of the tumour cell and the angiogenesis of the tumour.
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Cantaridina/análogos & derivados , Materia Medica/farmacología , Neovascularización Patológica/prevención & control , Neoplasias Gástricas/patología , Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Cantaridina/administración & dosificación , Cantaridina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Materia Medica/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microvasos , Trasplante de Neoplasias , Neoplasias Gástricas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To investigate the effects of dexamethasone on expression of matrix metalloproteinase-9 (MMP-9) in rats with acute lung injury induced by phosgene. METHODS: The rats were randomly divided into 3 groups: normal control group that consists of the rats with air exposure, phosgene group that consists of the rats with phosgene exposure and dexamethasone group that consists of the rats with phosgene exposure after 2.5 mg/kg dexamethasone being injected. Wet and dry ratio of the lung (W/D) was calculated, and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded at 2 h after exposure. The concentrations of MMP-9 in the serum and BALF were measured by enzyme-linked immunosorbent assay. The pathologic changes of lung tissues were observed under light microscopy. The immunohistochemistry and the RT-PCR were used to detect the contents of MMP-9 in the lung tissue. RESULTS: Compared with phosgene group, the lung W/D, protein content and WBC count in of BALF dexamethasone group was significantly decreased (P < 0.01). MMP-9 levels of the serum and BALF in dexamethasone group were (4.799 +/- 0.043) microg/L and (15.052 +/- 0.029) microg/L, respectively, which were significantly lower than those [(9.439 +/- 0.100) and (20.640 +/- 0.446) microg/L] in phosgene group (P < 0.01). Compared with phosgene group (2.789 +/- 0.282),the expression level (1.183 +/- 0.260) of lung MMP-9 mRNA in dexamethasone group was significantly lower than that in phosgene group (P < 0.01). Histological experimental results showed the marked hyperemia and thickening of alveolar walls and stroma cells infiltrating and more visible alveolar structure damage of alveolar walls in phosgene group while the alveolar structure and the alveolar walls were clear and slightly thickened with inflammatory cells in dexamethasone group. Immunohistochemical results showed that MMP-9 protein expression levels of lung and bronchus tissues in normal control group and dexamethasone group were weakly positive, which in phosgene group were strongly positive. CONCLUSION: Dexamethasone has a beneficial effects on acute lung injury induced by phosgene in rats due to the inhibiting MMP-9.
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Lesión Pulmonar Aguda/metabolismo , Dexametasona/uso terapéutico , Metaloproteinasa 9 de la Matriz/metabolismo , Fosgeno/toxicidad , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The straightforward synthesis of α-amino phosphine oxides via three-component reactions involving arynes, formamides and diarylphosphine oxides is disclosed. This method employs the aryne to activate formamide, without an external activating reagent, which is operationally simple under mild conditions with high efficiency. Furthermore, mechanistic perception suggests a cascade sequence including formal [2 + 2] cycloaddition of the aryne with a CîO bond, and a 1,4-addition of the H-P(O) compounds to the enamine intermediates.