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BACKGROUND: The mechanism of action of fire acupuncture and Chinese medicine in psoriasis is unclear. In this paper, the efficacy of the 2 therapies was compared through a comprehensive analysis of their recurrence rates for clinical reference. METHODS: In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM data from the establishment of the databases to May 2023. The study proposed to use randomized controlled trial research methods, excluding published literature, unpublished literature, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies. Data were processed using STATA 15.1 software. RESULTS: Our group previous study found that the clinical efficacy of the fire-acupuncture group was significantly improved compared to that of Chinese herbal medicine alone (RRâ =â 1.20, 95% CI: 1.13-1.27). Also, there were significant reductions in Psoriasis Area and Severity Index (PASI) score (SMDâ =â -1.04,95% CI: -1.48 to -0.60), area of skin damage (SMDâ =â -0.40,95% CI: -0.75 to -0.04), and pruritus (SMDâ = -1.04,95% CI: -1.32 to -0.76). Our previous study found that Dermatology Life Quality Index (DLQI) was significantly lower in the fire acupuncture group compared to herbal medicine alone (SMDâ =â -1.61,95% CI: -3.08 to -0.15). The combined analysis found that the recurrence rate was significantly lower in the fire-acupuncture group compared to herbal medicine alone (RRâ =â 0.21,95% CI:0.07-0.60). CONCLUSION: Fire needle can improve the efficacy of TCM in the treatment of psoriasis, including the area, severity and itching of skin lesions, and reduce the recurrence rate, which is worthy of clinical promotion.
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Terapia por Acupuntura , Medicina Tradicional China , Psoriasis , Psoriasis/tratamiento farmacológico , Psoriasis/terapia , Humanos , Terapia por Acupuntura/métodos , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia Combinada , Resultado del Tratamiento , Índice de Severidad de la EnfermedadRESUMEN
Vegetable oils are rich sources of polyunsaturated fatty acids and energy as well as valuable sources of human food, animal feed, and bioenergy. Triacylglycerols, which are comprised of three fatty acids attached to a glycerol backbone, are the main component of vegetable oils. Here, we review the development and application of multiple-level omics in major oilseeds and emphasize the progress in the analysis of the biological roles of key genes underlying seed oil content and quality in major oilseeds. Finally, we discuss future research directions in functional genomics research based on current omics and oil metabolic engineering strategies that aim to enhance seed oil content and quality, and specific fatty acids components according to either human health needs or industrial requirements.
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Brassica napus , Multiómica , Humanos , Brassica napus/genética , Ácidos Grasos/metabolismo , Aceites de Plantas/metabolismo , Triglicéridos/metabolismo , Semillas/metabolismoRESUMEN
The aim of the present study was to investigate the influence of stimulating food (SF), a Traditional Chinese Medicine term for a high protein, high fat diet, on psoriasis exacerbation. It was hypothesized that SF disposed psoriasis-like aggravation might be related to inflammatory pathways induction via gut dysbiosis. In the present study, mice were fed either an SF or normal diet for 4 weeks. In the last week, their back hair was removed to establish psoriasis-like dermatitis by imiquimod. After sacrifice, blood samples, alimentary tissues and skin lesions were collected and tested by enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Compared with normal diet groups, body weight and blood glucose of SF diet mice were not increased, but they exhibited higher modified Psoriasis Area and Severity Index scores and corresponding epithelial hyperproliferation. Unexpectedly, skin lesions showed abnormal lower protein expressions of Notch and TLR-2/NF-κB p65 signaling pathway, which was attributable to severe skin damage. No difference was observed in the structure and inflammatory cell infiltration of the gut between groups. Instead, macrophage polarization (M1/M2) in the gut of the SF diet group marked by high expression of CD11b (a marker of macrophage, M1) and mild low expression of MRC1 (a marker of macrophage, M2), which resulted in increased TNF-α, decreased IL-10, IL-35, and unchanged IL-17 in serum. Furthermore, serum derived from SF diet mice promoted translocation of NF-κB p65 in HaCaT cells, which indirectly suggested a systemic inflammation. These results suggested that mice fed a continuous SF diet for a time could change gut macrophage polarization, which secretes proinflammatory cytokines into blood circulation. Once transported to skin lesions, these cytokines activate psoriasis tissue resident immune cells and present as psoriasis exacerbation.
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BACKGROUND: Integrating medical resources is one of the explorations of medical mechanism reform to meet the needs of whole-cycle health management and is an important initiative in the current round of China's healthcare system reform. 2015 saw the construction of county medical communities to promote the balanced layout of medical resources, which opened a new exploration of the construction of an integrated healthcare service system in China. 2017 saw the promotion of the pilot construction of compact county medical communities in Zhejiang Province, China. OBJECTIVE: From the perspective of alleviating the financial burden on those in need of health services, the characteristics of chronic disease patients' access to health care and the composition and changing curve of the medical cost burden are analyzed to provide a basis for the construction path of an integrated health care service system. METHODS: A retrospective cohort study was conducted to select 5739 permanent residents who met the inclusion and exclusion criteria in Z town, H city, Zhejiang province. This population's health insurance utilization data from 2015 to 2018 were retrieved, and their average annual costs, cost composition, and health insurance payments were analyzed. RESULTS: The average annual growth rates of medical insurance and out-of-pocket costs before and after the implementation of the Medical Community were 12.85% and 9.72%, respectively. The increase narrowed significantly after the construction of the Medical Community, with the ringgit growth rate dropping to 2.73% in 2018. The top three medical expenses that accounted for the highest percentage were drug, consultation, and treatment fees. The frequency of visits to primary health care consulting hospitals has increased yearly. CONCLUSIONS: By implementing various measures to strengthen the grassroots level, patients' choice of primary care has increased year by year in the early stages of the construction of the Medical Community. From the perspective of cost control, strengthening the regulation of drugs and tests and restricting the use of high-value consumables can further reduce medical costs and ease their financial burden.
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Estrés Financiero , Servicios de Salud , Humanos , Estudios Retrospectivos , Atención a la Salud , Enfermedad Crónica , ChinaRESUMEN
Long-term rigorous musical training promotes various aspects of spoken language processing. However, it is unclear whether musical training provides an advantage in recognizing segmental and suprasegmental information of spoken language. We used vowel and tone violations in spoken unfamiliar seven-character quatrains and a rhyming judgment task to investigate the effects of musical training on tone and vowel processing by recording ERPs. Compared with non-musicians, musicians were more accurate and responded faster to incorrect than correct tones. Musicians showed larger P2 components in their ERPs than non-musicians during both tone and vowel processing, revealing increased focused attention on sounds. Both groups showed enhanced N400 and LPC for incorrect vowels (vs. correct vowels) but non-musicians showed an additional P2 effect for vowel violations. Moreover, both groups showed enhanced LPC for incorrect tones (vs. correct tones) but only non-musicians showed an additional N400 effect for tone violations. These results indicate that vowel/tone processing is less effortful for musicians (vs. non-musicians). Our study suggests that long-term musical training facilitates speech tone and vowel processing in a tonal language environment by increasing the attentional focus on speech and reducing demands for detecting incorrect vowels and integration costs for tone changes.
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Música , Percepción del Habla , Femenino , Humanos , Masculino , Estimulación Acústica , Electroencefalografía , Potenciales Evocados , Lenguaje , Poesía como AsuntoRESUMEN
BACKGROUND: The aging of the population has made the health problems of the elderly increasingly prominent, and their health needs are increasing. Existing studies on health resource integration approaches are mostly incomplete in assessing the health service capacity from the perspective of the health service provider. OBJECTIVE: The unmet health needs of the elderly were sampled and analyzed from the perspective of health service demanders. To explore how to build an integrated medical organization structure to better meet the health needs of the elderly. METHODS: A whole-group sampling method was used to conduct a questionnaire survey of 1527 older adults in N district of H city, Zhejiang province, China, to cross-sectionally analyze their current status of unmet health needs. RESULTS: The survey and analysis found that the needs of the elderly in this community to obtain disease-related knowledge, rational exercise, a healthy diet, and access to health information were not met. There were more patients with chronic diseases, and the top three chronic disease prevalence rates were hypertension (40.2%), dyslipidemia (8.4), and diabetes (7%). Chronic disease co-morbidities accounted for 13.3%. CONCLUSION: The relatively independently set up health service system at the present stage in China can no longer fully meet the health needs of the elderly, and the health service providers should provide integrated and continuous health services to meet the needs of whole-cycle health management. Therefore, we believe that effectively integrating various health service providers in the region and building an integrated health service organization with general practitioners as the core may be a solution to the current situation of unmet health needs of the elderly.
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Recursos en Salud , Servicios de Salud , Humanos , Anciano , Estudios Transversales , China/epidemiología , Enfermedad CrónicaRESUMEN
Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs, whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology. Here, a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics. Multiple interaction forces are found to drive the co-assembly process. Moreover, DOX release from the nanoassembly can be well controlled by the acidic tumor microenvironment and laser irradiation, resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo. As expected, the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells (4T1) on BALB/c mice, owing to synergistic chemo-photothermal therapy. More interestingly, DiR and DOX synergistically induce immunogenic cell death (ICD) of tumor cells after treatment, enabling the mice to acquire immune memory against tumor growth and recurrence. Such a facile nanoassembly technique provides a novel multimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.
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Musical expertise is known to affect speech perception at units below clause/sentence. This study investigated whether the musician's advantage extends to a higher and more central level of speech processing (i.e., clause segmentation). Two groups of participants (musician vs. nonmusician) were presented with sentences that contain an internal clause boundary. The acoustic correlates of the boundary were manipulated in six conditions: all-cue, pause-only, final-lengthening-only, pitch-reset-only, pause-and-final-lengthening-in-combination, and no-cue conditions. Participants were asked to judge whether the sentence they heard had an internal boundary. Results showed that the musicians detected more boundaries than the nonmusicians in the all-cue and the pause-only conditions, but fewer boundaries in the no-cue condition. Further analyses of cue weight showed that both musicians and nonmusicians placed more importance on pause than the other two cues, but this weighting bias was more pronounced for the musicians. These results suggest that music training is associated with increased perceptual acuity not only to the acoustic markings of speech boundaries but also to the weighting of the cues. Our findings extend the role of musical expertise to sentence-level speech processing.
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Música , Percepción del Habla , Estimulación Acústica , Humanos , Lenguaje , Percepción de la Altura Tonal , HablaRESUMEN
OBJECTIVE: To investigate the efficacy and safety of the antithrombotic therapy using the oral anticoagulant rivaroxaban and clopidogrel in Chinese patients with acute coronary syndrome complicated with atrial fibrillation after percutaneous coronary intervention. METHODS: A total of 100 patients were selected. Patients were randomly divided into two groups: the treatment group (rivaroxaban group) received a therapy of rivaroxaban and clopidogrel. The control group (warfarin group) receivied a combined treatment of warfarin, clopidogrel, and aspirin. The primary outcome endpoint was evaluated based on the adverse cardiac and cerebrovascular events within 12 months. RESULTS: A total of 8 (8.00%) main adverse cardiac and cerebrovascular events occurred during the 12 months of follow-up, including 5 (9.80%) in the warfarin group and 3 (6.10%) in the rivaroxaban group. The risk of having main adverse cardiac and cerebrovascular events in the two groups was comparable (P = 0.479). A total of 9 patients (9.00%) were found to have bleeding events, among which 8 patients (15.7%) were in the warfarin group, whereas only 1 patient (2.00%) was in the rivaroxaban group. Therefore, the risk of bleeding in the warfarin group was significantly higher than that in the rivaroxaban group (P = 0.047). CONCLUSIONS: In Chinese patients with acute coronary syndrome complicated with atrial fibrillation, the efficacy of the dual therapy of oral anticoagulant rivaroxaban plus clopidogrel after percutaneous coronary intervention was similar to that of the traditional triple therapy combined with warfarin, aspirin and clopidogrel, but it has a better safety property, which has potential to widely apply to antithrombotic therapy after PCI.
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Síndrome Coronario Agudo/terapia , Fibrilación Atrial/tratamiento farmacológico , Clopidogrel/administración & dosificación , Intervención Coronaria Percutánea , Cuidados Posoperatorios/métodos , Rivaroxabán/administración & dosificación , Accidente Cerebrovascular/prevención & control , Síndrome Coronario Agudo/diagnóstico , Adulto , Anciano , Fibrilación Atrial/complicaciones , China/epidemiología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Ecocardiografía , Electrocardiografía , Inhibidores del Factor Xa/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
Species of Fe in the sediments from 21 sections of the Yellow River have been analyzed utilizing the so-called sequential extraction approach. The correlation between iron and phosphorus was analyzed, and the risk of release phosphorus was predicted. The results show that the content of residual iron (Feresidual) in the sediments is the highest, accounting for more than 92.55% of total iron (∑Fe) (the sum of the iron contents in each form is the total iron). Ca-bound phosphorous (PCa) is equal to the sum of authigenic calcium and phosphorus (Paut) and detritus calcium phosphorus (PDe), accounting for more than 73.01% of ∑P, in which PDe accounts for more than 90.91% of PCa, which is the main component of PCa and the main component of ∑P; Fewater in sediments is closely related to Porg, and Feex is closely related to Pex and PAl, which is an important factor to control the release of endogenous phosphorus. The extremely significant positive correlation between Feresidual and Paut and PDe in sediments is that they are affected by complex geological conditions in the Yellow River Basin. Judging by the ratio of ∑Fe/∑P combined with the influence of human factors, the release of phosphorus in sediments of most reaches of the Yellow River is controlled by iron, while the release of phosphorus is inhibited. Sediments in Xigu section H4, Zhongwei section H5, Haibowan section H7, three Sanshenggong section H8, Liulin section H13, and Tongguan section H16 of the Yellow River have certain phosphorus release risks, because phosphorus release is not only controlled by iron but also influenced by human factors, such as industrial and agricultural production level and artificial dam construction.
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Ríos , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Sedimentos Geológicos , Humanos , Hierro , Fósforo/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Traditional genetic studies focus on identifying genetic variants associated with the mean difference in a quantitative trait. Because genetic variants also influence phenotypic variation via heterogeneity, we conducted a variance-heterogeneity genome-wide association study to examine the contribution of variance heterogeneity to oil-related quantitative traits. We identified 79 unique variance-controlling single nucleotide polymorphisms (vSNPs) from the sequences of 77 candidate variance-heterogeneity genes for 21 oil-related traits using the Levene test (P < 1.0 × 10-5 ). About 30% of the candidate genes encode enzymes that work in lipid metabolic pathways, most of which define clear expression variance quantitative trait loci. Of the vSNPs specifically associated with the genetic variance heterogeneity of oil concentration, 89% can be explained by additional linked mean-effects genetic variants. Furthermore, we demonstrated that gene × gene interactions play important roles in the formation of variance heterogeneity for fatty acid compositional traits. The interaction pattern was validated for one gene pair (GRMZM2G035341 and GRMZM2G152328) using yeast two-hybrid and bimolecular fluorescent complementation analyses. Our findings have implications for uncovering the genetic basis of hidden additive genetic effects and epistatic interaction effects, and we indicate opportunities to stabilize efficient breeding and selection of high-oil maize (Zea mays L.).
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Variación Genética/genética , Zea mays/genética , Aceite de Maíz/genética , Aceite de Maíz/metabolismo , Epistasis Genética/genética , Genes de Plantas/genética , Genes de Plantas/fisiología , Sitios Genéticos/genética , Estudio de Asociación del Genoma Completo , Metabolismo de los Lípidos/genética , Polimorfismo de Nucleótido Simple/genética , Carácter Cuantitativo HeredableRESUMEN
Maize ( L.) kernel oil provides high-quality nutrition for animal feed and human health. A certain number of maize breeding programs seek to enhance oil concentration and composition. Genomic selection (GS), which entails selection based on genomic estimated breeding values (GEBVs), has proven to be efficient in breeding programs. Here, we estimate the robustness of predictions for the oil traits of maize kernels in biparental recombination inbred lines (RILs) using a GS model built based on an association population. Most statistical models, including ridge regression-best linear unbiased prediction (RR-BLUP), showed high prediction accuracy in the training population through a cross validation procedure. The training population size was more important than marker density and a statistical model for prediction performance. Using the optimized GS model, prediction of the biparental RIL population showed medium-high prediction accuracy (0.68) compared with prediction using only oil associated markers ( = 0.43). The potential to apply the GS model to another RIL population that is genetically less related to the training population was also examined, showing promising prediction accuracy in the top selected lines. Our results proved that genomic prediction using existing data is robust for the prediction of polygenic traits with moderate to high heritability.
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Aceite de Maíz/genética , Zea mays/genética , Marcadores Genéticos , Genoma de Planta , Modelos Genéticos , Modelos Estadísticos , Fenotipo , Fitomejoramiento , Zea mays/químicaRESUMEN
BACKGROUND Radix Tetrastigma Hemsleyani Flavone (RTHF) has detoxification and anti- inflammation activity and is widely used. Here, we report that RTHF inhibits cell proliferation and induces apoptosis in cutaneous squamous cell carcinoma A431 cells and is a potential strategy for cancer therapy. MATERIAL AND METHODS A431 cells were cultured in different concentrations of RTHF. The inhibition of cell proliferation was assessed by MTT assay, cell apoptosis was shown through FCM, and cell invasion was assessed by Transwell methods. Enzyme proteasome assay was used to detect the activity of proteasome and DUB. Expression of apoptosis-related and ubiquitin proteasome pathway-associated proteins were assessed by PCR and Western blot. RESULTS RTHF obviously suppressed the proliferation and induced apoptosis of A431 cells in a dose-dependent manner. Transwell assay showed that RTHF inhibited the cell metastasis significantly. Enzyme proteasome assay show that the RTHF treatment of activity of proteasome and DUB was significantly lower than in control. RTHF increased the expression of Bax and inhibited Bcl-2, pro-caspase3, and pro-caspase9 activity. The expression of USP14, UCHL5, and POH1 decreased and ub-prs increased significantly in the treatment group. CONCLUSIONS Our study reveals that RTHF-mediated inhibition of DUBs and proteasome may provide a potential strategy for cancer therapy.
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Medicamentos Herbarios Chinos/uso terapéutico , Flavonas/metabolismo , Flavonas/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/patología , Caspasa 3/efectos de los fármacos , Caspasa 9/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Medicina Tradicional China/métodos , Invasividad Neoplásica , Plantas Medicinales/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Transducción de Señal , Ubiquitina Tiolesterasa/metabolismo , Proteína X Asociada a bcl-2/efectos de los fármacosRESUMEN
OBJECTIVE: To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. METHODS: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data. RESULTS: The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. CONCLUSIONS: QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.
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Arsenicales/uso terapéutico , Linaje de la Célula , Metilación de ADN/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Trastornos Leucocíticos/tratamiento farmacológico , Trastornos Leucocíticos/genética , Arsenicales/administración & dosificación , Arsenicales/farmacología , Linaje de la Célula/efectos de los fármacos , Desmetilación , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Femenino , Ontología de Genes , Humanos , Masculino , Persona de Mediana Edad , Polvos , Resultado del TratamientoRESUMEN
Human immunodeficiency virus type 1 (HIV-1) is responsible for the majority of HIV infections worldwide, and we still lack a cure for this infection. Blocking the interaction of HIV-1 and its primary receptor CD4 is one strategy for identifying new anti-HIV-1 entry inhibitors. Here we report the discovery of a novel ligand that can inhibit HIV-1 entry and infection via CD4. Biological and computational analyses of this inhibitor and its analogs, using bioactivity evaluation, Rule of Five (RO5), comparative molecular field analysis (CoMFA)/comparative molecular similarity index analysis (CoMSIA) models, and three-dimensional quantitative structure-activity relationship (3D-QSAR), singled out compound 3 as a promising lead molecule for the further development of therapeutics targeting HIV-1 entry. Our study demonstrates an effective approach for employing structure-based, rational drug design techniques to identify novel antiviral compounds with interesting biological activities.
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Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacología , Antígenos CD4/metabolismo , VIH-1/fisiología , Internalización del Virus/efectos de los fármacos , Fármacos Anti-VIH/química , Sitios de Unión/efectos de los fármacos , Antígenos CD4/química , Línea Celular , Biología Computacional , Simulación por Computador , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , VIH-1/efectos de los fármacos , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Unión Proteica/efectos de los fármacos , Relación Estructura-Actividad CuantitativaRESUMEN
The anti-lung cancer activity of volatile oil from Alpinia officinarum (VOAO) and the underlying mechanism has not been studied. Herein, VOAO was extracted by steam distillation and its components were identified by GC-MS analysis. Cells viability was measured by an MTT assay and the cell survival capacity was tested via a colony formation assay. Apoptosis cells were detected using the Annexin V-FITC/PI method. Hoechst 33342 cell unclear staining was employed to evaluate the nuclear morphology change. The mitochondrial membrane potential was detected by a JC-1 staining assay. Bcl-2, Mcl-1 and cleaved caspase-3 proteins were quantified by immune blotting. Furthermore, VOAO anti-cancer activity was evaluated on an A549 cell xenograft nude mice model. Our results have revealed that VOAO could inhibit the cell viability of lung carcinoma cells and the colony formation capacity. VOAO downregulates Bcl-2 and Mcl-1 and triggers dysfunction of the mitochondrial membrane potential. VOAO further activates caspase-3 cleavage and induces lung cancer cells apoptosis. In addition, VOAO administration significantly suppresses lung cancer growth in xenograft mice without obvious hepatotoxicity. We conclude that VOAO could be an effective, low cytotoxicity natural component for treatment of lung carcinoma.
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Alpinia/química , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Pulmón/efectos de los fármacos , Aceites Volátiles/uso terapéutico , Animales , Anticarcinógenos/administración & dosificación , Anticarcinógenos/efectos adversos , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacología , Carcinoma/metabolismo , Carcinoma/patología , Carcinoma/prevención & control , Línea Celular Tumoral , Forma del Núcleo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Desnudos , Proteínas de Neoplasias/metabolismo , Aceites Volátiles/administración & dosificación , Aceites Volátiles/efectos adversos , Aceites Volátiles/farmacología , Distribución Aleatoria , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND/AIMS: Both physiologic remodeling and pathologic regeneration of cartilage tissue rely upon chondrocyte functions and are benefited from factors that promote viability and inhibit apoptosis of the cell, and associated mechanisms. High level of reactive oxygen species (ROS) and proinflammatory cytokines activate apoptosis signaling and initiate cell death, which can be attenuated by antioxidants. This study examined the effect of catalase (CAT) on ROS and tumor necrosis factor-α (TNF-α)-induced apoptosis in human C28/I2 chondrocytes cultured in monolayer. METHODS: Chondrocytes were treated with diluted CAT in the presence or absence of TNF-α and compared to untreated cells. Levels of hydrogen peroxide (H2O2) and mitochondrial membrane potential (Δψm) were measured using fluorescent labeling, cell apoptosis was assayed by flow cytometry using Annexin V/propidium iodide (PI) staining, gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR) and the proteins were investigated by Western blotting. RESULTS: CAT effectively reduced the intracellular ROS caused by the monolayer culture system, enhanced the Δψm depending on the presence of TNF-α and promoted morphological features at sub-cellular level. CAT also attenuated the TNF-α-upregulated expression of factors/mediators of extrinsic cell death cascade and apoptotic caspases, ultimately resulted in promoted cellular viability. CONCLUSION: The anti-apoptotic effect of CAT on chondrocytes via scavenging ROS and suppressing TNF-α-induced cell apoptosis by TNF/TNF receptor (TNFR) mediated death signaling pathway and potentiate CAT as a complementary agent beneficial to cartilage remodeling and regeneration in vivo, and cell-based therapies of cartilage repair demanding viable cells expanded ex vivo.
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Apoptosis/efectos de los fármacos , Catalasa/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Condrocitos/citología , Condrocitos/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer antibiotics with novel scaffolds. As historically many commercial drugs were derived from natural products, discovery of antimicrobial agents from complex natural product structures still holds a great promise. Herein, we report the total synthesis of natural albomycins δ1 (1a), δ2 (1b), and ε (1c), which validates the structures of these peptidylnucleoside compounds and allows for synthetic access to bioactive albomycin analogs. The efficient synthesis of albomycins enables extensive evaluations of these natural products against model bacteria and clinical pathogens. Albomycin δ2 has the potential to be developed into an antibacterial drug to treat Streptococcus pneumoniae and Staphylococcus aureus infections.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Ferricromo/análogos & derivados , Antiinfecciosos/química , Técnicas de Química Sintética , Evaluación Preclínica de Medicamentos/métodos , Ferricromo/química , Ferricromo/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
One new sorbicillin derivative, 2-deoxy-sohirnone C (1), one new diketopiperazine alkaloid, 5S-hydroxynorvaline-S-Ile (2), and two naturally occurring diketopiperazines, 3S-hydroxylcyclo(S-Pro-S-Phe) (3) and cyclo(S-Phe-S-Gln) (4), together with three known compounds were isolated from the Chinese mangrove endophytic fungus Penicillium sp. GD6. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison with literature data. The absolute configuration of 3-hydroxyl moiety in 3 was determined by Mosher's method, while the absolute stereochemistry of 2 and 4 was established by comparison with the CD spectra of natural and synthesized diketopiperazines. Compound 1 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with a MIC value of 80 µg·mL-1.
Asunto(s)
Antibacterianos/farmacología , Dicetopiperazinas/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Penicillium/química , Resorcinoles/química , Resorcinoles/farmacología , Rhizophoraceae/microbiología , Alcaloides/química , Alcaloides/aislamiento & purificación , Antibacterianos/química , Antibacterianos/aislamiento & purificación , China , Dicroismo Circular , Dicetopiperazinas/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Resorcinoles/aislamiento & purificación , HumedalesRESUMEN
Simulation experiments were conducted using sediments collected from the Taihu Lake to determine the combined effects of submerged macrophytes Ceratophyllum demersum and phosphate-solubilizing bacteria (PSB) strain XMT-5 (Rhizobium sp.) on phosphorus (P) concentrations in overlying waters and sediments. After 30 days of experimental incubation, the total phosphorus (TP) and dissolved total phosphorus (DTP) concentrations of the overlying water subjected to AMB and AHMB treatments (both with the combined effects of PSB cells and submerged macrophytes) were generally lower than those of the AM (with individual effects of inoculated C. demersum) and AB (with individual effects of a smaller amount of inoculated PSB cells) control treatments but higher than that of the A (with no effects of inoculated PSB cells or C. demersum) and AHB (with individual effects of a larger amount of inoculated PSB) control treatments. The TP contents of the sediment in the AMB and AHMB treatments were significantly lower than those of the other control treatments. The TP contents of the C. demersum cocultured with the PSB strain XMT-5 cells in the AMB and AHMB treatments were all significantly higher than that of the AM treatment, indicating the enhancement of P uptake by submerged plants inoculated with PSB. The bacterial diversity structures of the rhizosphere sediment subjected to different treatments were also analyzed by the high-throughput sequencing method. According to the ACE and Chao 1 indices, the bacterial diversity in the AMB and AHMB treatments were the highest. Although many sources contributed to the decrease in the nutrient loads of the lake sediment, harvesting macrophytes inoculated with PSB cells prior to their senescence might constitute a significant in-lake measure for reducing internal P load.