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Glomalin-related soil protein (GRSP) is a stable and persistent glycoprotein secreted by arbuscular mycorrhizal fungi that plays an important role in sequestering soil organic carbon (SOC) and improving soil quality. Rapid urbanization disturbs and degrades the soil quality in the greenspace. However, few studies have investigated the effects of urbanization on GRSP and its influencing factors. This study selected impervious surface area as a measure of urbanization intensity. A total of 184 soil samples were collected from the 0-20 cm soil layer in the greenspace of Nanchang, China (505 km2). The GRSP content, soil properties, urban forest characteristics, and land-use configuration were determined. The total GRSP (TG) and easily extractable GRSP (EEG) contents were 2.38 and 0.57 mg g-1, respectively. TG and EEG decreased by 16.22% and 19.35%, respectively, from low to heavy urbanized areas. Moreover, SOC decreased from 39.9 to 1.4 mg g-1, while EEG/SOC and TG/SOC increased by approximately 17% and 34%, respectively, indicating the significant contribution of GRSP to the SOC pool. Pearson and redundancy analysis showed that GRSP was positively correlated with SOC, phosphorus, nitrogen, vegetation richness, and tree height, but negatively correlated with pH, bulk density, and impervious area. The partial least squares path model demonstrated that urbanization affected soil properties, forest characteristics, and land use factors, resulting in GRSP changes. This study clarifies the key factors of urbanization that affect GRSP and provides insight for urban greenspace soil improvement from the new perspective of enhancing the GRSP content.
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Micorrizas , Solo , Carbono/análise , China , Proteínas Fúngicas/análise , Micorrizas/química , Micorrizas/metabolismo , Parques Recreativos , Solo/química , UrbanizaçãoRESUMO
This article provides an overview of the intersection of open data and public health by first defining open government data, public health data, and other key concepts and relevant terminologies. There are differing perceptions on the urgency and importance of the openness of public health data. It has been established that disease outbreaks such as happened during the Ebola and Zika virus epidemics are indicative of the need for countries to develop a framework that will provide guidance for the management of public health data. Such a framework should ensure that data collected during public health emergencies are accessible to the appropriate authorities and in a form that can help with timely decision-making during such public health crises. In this article, we highlight available open data policies across many countries, including in the Americas. Our analysis shows that there are currently no articulated policy guidelines for the collection and management of public health data across many countries, especially in Latin America. We propose that any national data governance strategy must address potential benefits, possible risks, examples of data that could be shared, and the attributes of such data. Finally, we stress that the key concern in the Americas should be the development of regional frameworks for open data in public health that can be adopted or adapted by each country through appropriate national or subnational policies and strategies.
Este artículo ofrece un panorama de la intersección entre los datos abiertos y la salud pública al definir en primer lugar qué son los datos gubernamentales abiertos, los datos sobre salud pública y otros conceptos fundamentales y términos pertinentes. Hay percepciones dispares sobre la premura y la importancia de la apertura de los datos sobre salud pública. Se ha establecido que los brotes de ciertas enfermedades, como las epidemias por los virus del Ébola y del Zika, demuestran la necesidad de que los países elaboren un marco que oriente la gestión de los datos sobre salud pública. Dicho marco debe garantizar que los datos recopilados durante las emergencias de salud pública sean accesibles para las autoridades competentes y en una forma que contribuya a la toma oportuna de decisiones durante estas crisis de salud pública. En este artículo, destacamos las políticas de datos abiertos existentes en diversos países, incluidos varios de la Región de las Américas. Nuestro análisis muestra que actualmente en muchos países no hay directrices articuladas de políticas públicas para la recopilación y gestión de los datos sobre salud pública, en especial en América Latina. Proponemos que toda estrategia nacional de gobernanza relativa a los datos debe abordar los posibles riesgos y beneficios, ejemplos de los datos que podrían compartirse y los atributos de tales datos. Por último, subrayamos que el interés fundamental en la Región de las Américas debe ser la creación de marcos regionales para datos abiertos sobre salud pública que cada país pueda adoptar o adaptar mediante las políticas y estrategias nacionales o subnacionales apropiadas.
Este artigo expõe um panorama da interseção entre dados abertos e saúde pública, começando por definir o que são dados abertos do governo, dados de saúde pública e outros conceitos fundamentais e terminologias relevantes. Existem distintas percepções quanto à premência e à importância da abertura de dados de saúde pública. Reconhecidamente, os surtos de doenças, como os ocorridos nas epidemias do vírus Ebola e vírus zika, apontam para a necessidade de os países desenvolverem uma estrutura para direcionar o gerenciamento dos dados de saúde pública. Esta estrutura deve servir para garantir que os dados coletados nas emergências de saúde pública estejam acessíveis às autoridades cabíveis em uma forma que possa subsidiar a tomada de decisão oportuna durante tais crises de saúde pública. No artigo, destacam-se as políticas de dados abertos de diversos muitos países, inclusive dos países na Região das Américas. Nossa análise demonstra que vários países, sobretudo na América Latina, não possuem diretrizes claramente definidas de políticas para a coleta e o gerenciamento de dados de saúde pública. Recomendamos que qualquer estratégia nacional de governança de dados nacionais precisa contemplar os possíveis benefícios e riscos, explicitar os dados a ser compartilhados assim como descrever os atributos de tais dados. Por fim, salientamos que a principal preocupação nas Américas deve ser o desenvolvimento de estruturas regionais para dados abertos em saúde pública que possam ser postas em prática ou adaptadas por cada país como parte de estratégias e políticas nacionais ou subnacionais adequadas.
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BACKGROUND: The expression of RKIP, TGM2, and CMTM4 in oral squamous cell carcinoma (OSCC) and normal oral tissues was detected and their correlations were analyzed. The relationships between RKIP, TGM2, and CMTM4 and the clinicopathological parameters and prognosis of patients were analyzed. METHODS: Seventy cancerous and adjacent normal tissue samples were selected, recorded in the pathology department, and embedded in paraffin. Protein expression was detected by immunohistochemistry. Statistical software (SPSS 25.0, IBM Corporation) was used for the statistical analysis. The chi-squared (χ2) test was used to analyze the expression of RKIP, TGM2, and CMTM4 proteins and their clinicopathological features. Differences in RKIP, TGM2, and CMTM4 protein levels between OSCC and normal tissues were compared using a χ2 test. Survival analysis was performed using the Kaplan-Meier method, and differences between survival curves were determined using the log-rank test. The effects of RKIP, TGM2, and CMTM4 expression on patient prognosis were analyzed using a multivariate Cox proportional hazards regression model. Pâ <â .05 was considered statistically significant. RESULTS: The expression level of RKIP correlated with age and clinical stage (Pâ <â .05). TGM2 was associated with clinical stage and lymph node metastasis (Pâ <â .05). The expression of CMTM4 increased with a decrease in cancer differentiation. Kaplan-Meier survival analysis suggested that the positive expression of TGM2 and CMTM4 may predict poor prognosis in patients with OSCC. The multivariate Cox proportional hazards regression model suggested that TGM2 could be an independent prognostic factor for patients with OSCC. CONCLUSION: Combined expression of TGM2 and CMTM4 can be used as an indicator to evaluate the risk of metastasis and prognosis of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas com Domínio MARVEL , Neoplasias Bucais/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Infrared solar cells (IRSCs), capable of converting low-energy infrared photons to electron-hole pairs, are promising infrared optoelectronic devices because of their extended utilization region of the solar to short-wavelength infrared region. For PbS QDs IRSCs, charge extraction loss, easily generated at the interfaces, has been one of the dominate obstacles impeding the improvement of device efficiencies due to too many trap states and mismatched energy levels between the photoactive layer and electron transport layer (ETL). Herein, an advanced ZnO ETL was developed to improve the extraction of photogenerated charges from the PbS QD photoactive layer to ETLs. The advanced ETL film exhibited effectively suppressed trap states and better-matched energy levels compared with the QD layer. As a consequence, high-performance PbS QD IRSCs with the highest infrared power conversion efficiencies of 1.26% under 1100 nm filtered solar illumination are achieved, suggesting an effective and facile route for enhancing the charge extraction in infrared photovoltaics.
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Infrared (IR) solar cells, capable of converting low-energy IR photons to electron-hole pairs, are promising optoelectronic devices by broadening the utilization range of the solar spectrum to the short-wavelength IR region. The emerging PbS colloidal quantum dot (QD) IR solar cells attract much attention due to their tunable band gaps in the IR region, potential multiple exciton generation, and facile solution processing. In PbS QD solar cells, ZnO is commonly utilized as an electron transport layer (ETL) to establish a depleted heterostructure with a QD photoactive layer. However, band gap shrinkage of large PbS QDs makes it necessary to tailor the behaviors of the ZnO ETL for efficient carrier extraction in the devices. Herein, the characteristics of ZnO ETL are efficiently and flexibly tailored to match the QD layer by handily adjusting the postannealing process of ZnO ETL. With a suitable temperature, the well-matched energy level alignment and suppressed trap states are simultaneously achieved in the ZnO ETL, effectively reducing the nonradiative recombination and accelerating the electron injection from the QD layer to ETL. As a consequence, a high-performance PbS QD photovoltaic device with power conversion efficiencies (PCEs) of 10.09% and 1.37% is obtained under AM 1.5 and 1100 nm filtered solar illumination, demonstrating a simple and effective approach for achieving high-performance IR photoelectric devices.
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INTRODUCTION: MicroRNAs (miRNAs) involve in destabilising messenger RNA or repressing translation of target molecules. Ginger-derived exosome-like nanoparticles (GELNs) play a crucial role in modulating intestinal inflammation. Moreover, GELNs contain highly heterogeneous miRNA. However, the role of miRNAs derived from GELNs in immunomodulation remains unclear. OBJECTIVES: This study aimed to elucidate the molecular basis of the unique biological effects mediated by miRNA derived from GELNs on macrophages. METHODS: GELNs were isolated using a combination of commercial exosome isolation kits and the differential centrifugation method, and the lipid composition of GELNs was determined using liquid chromatography-mass spectrometry. Subsequently, PKH26 labelled GELNs were taken up by macrophages. Furthermore, the modulation of inflammatory and immune responses by GELNs or osa-miR164d was assessed through the RNA-seq, RT-qPCR, online databases, and dual luciferase reporter assays to explore the underlying mechanisms of osa-miR164d. Biomimetic exosomes loaded with osa-miR164d were prepared using a microfluidic mixing device and systematically characterized. The therapeutic effects of osa-miR164d on relieving colitis were evaluated. RESULTS: We report for the first time that GELNs-derived osa-miR164d is a regulatory factor of reprogramming macrophage polarization, thereby inhibiting the intestinal inflammatory response. Mechanistically, osa-miR164d directly targets the 3'-UTRs of TAB1, which regulates macrophage polarization through the downregulation of NF-κB expression. In addition, We have designed a biomimetic exosome mimicking GELNs to deliver osa-miR164d (osa-miR164d-MGELNs). Notably, the osa-miR164d-MGELNs can efficiently reprogram macrophages to alleviate colitis-related symptoms. CONCLUSION: Our findings enhance the systematic understanding of how GELNs-derived osa-miR164d mediates cross-kingdom communication and provide an original engineering paradigm for mimicking GELNs to transfer miRNA.
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Broccoli contains an amount of biologically active substances, which bring beneficial effects on human health. Plant extracellular vesicles have been shown to be novel key factors in cancer diagnosis and tumor therapy. To date, the challenge of overcoming chemoresistance to 5-fluorouracil (5-FU) to facilitate the clinical management of colorectal cancer (CRC) has not been successful. Nevertheless, the functions of broccoli extracellular vesicles (BEVs) in the progression of CRC and 5-FU resistance are predominantly unclear. Herein, we showed that BEVs isolated from broccoli juice were effectively taken up by colorectal cancer HT-29 cells. The co-administration of BEVs and 5-FU significantly inhibited the proliferation and migration of colorectal cancer HT-29 cells, effectively blocking cell cycle progression. Furthermore, the co-administration of BEVs and 5-FU induced apoptosis by stimulating ROS production and disrupting mitochondrial function. Importantly, we found that BEVs reversed 5-FU resistance in HT-29 cells by suppressing the abnormal activation of the PI3K/Akt/mTOR signaling pathway. Collectively, our findings represent a novel strategy for utilizing BEVs to improve the efficacy of colorectal cancer treatment and enhance 5-FU chemosensitivity.
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Brassica , Neoplasias do Colo , Neoplasias Colorretais , Humanos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Neoplasias Colorretais/metabolismo , Brassica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Colo/tratamento farmacológico , Apoptose , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Ischaemic stroke (IS) is the second leading cause of death and a major cause of disability worldwide. Currently, the clinical management of IS still depends on restoring blood flow via pharmacological thrombolysis or mechanical thrombectomy, with accompanying disadvantages of narrow therapeutic time window and risk of haemorrhagic transformation. Thus, novel pathophysiological mechanisms and targeted therapeutic candidates are urgently needed. The autophagy-lysosomal pathway (ALP), as a dynamic cellular lysosome-based degradative process, has been comprehensively studied in recent decades, including its upstream regulatory mechanisms and its role in mediating neuronal fate after IS. Importantly, increasing evidence has shown that IS can lead to lysosomal dysfunction, such as lysosomal membrane permeabilization, impaired lysosomal acidity, lysosomal storage disorder, and dysfunctional lysosomal ion homeostasis, which are involved in the IS-mediated defects in ALP function. There is tightly regulated crosstalk between transcription factor EB (TFEB), mammalian target of rapamycin (mTOR) and lysosomal function, but their relationship remains to be systematically summarized. Notably, a growing body of evidence emphasizes the benefits of naturally derived compounds in the treatment of IS via modulation of ALP function. However, little is known about the roles of natural compounds as modulators of lysosomes in the treatment of IS. Therefore, in this context, we provide an overview of the current understanding of the mechanisms underlying IS-mediated ALP dysfunction, from a lysosomal perspective. We also provide an update on the effect of natural compounds on IS, according to their chemical structural types, in different experimental stroke models, cerebral regions and cell types, with a primary focus on lysosomes and autophagy initiation. This review aims to highlight the therapeutic potential of natural compounds that target lysosomal and ALP function for IS treatment.
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STUDY OBJECTIVES: Menopause is associated with nighttime sleep fragmentation, declining estradiol, and impaired cognition. In a model of pharmacologically induced estradiol suppression mimicking menopause, we examined the impact of menopause-pattern sleep fragmentation on daytime neurobehavioral performance and sleepiness in premenopausal women. METHODS: Twenty premenopausal women completed two five-night inpatient studies in the mid-to-late follicular phase (estrogenized) and after pharmacological estradiol suppression (hypo-estrogenized). During each study, participants had an uninterrupted 8-hour sleep opportunity for two nights, followed by three nights where sleep was experimentally fragmented to mimic menopause-pattern sleep disturbance, and during which the sleep opportunity was extended to prevent shortening of the sleep duration. Neurobehavioral performance and subjective sleepiness were measured using the Psychomotor Vigilance Task and Karolinska Sleepiness Scale (KSS). RESULTS: Compared to unfragmented sleep, sleep fragmentation increased attentional lapses (+â 0.6 lapses, pâ <â .05), slowed reaction time (+â 9.4 milliseconds, pâ <â .01), and increased daytime sleepiness (+â 0.5 KSS score, pâ <â .001). Estradiol suppression increased attentional lapses (+â 0.8; pâ <â .001) and reaction time (+â 12.3, pâ <â .01) but did not significantly affect daytime sleepiness. The effect of sleep fragmentation on neurobehavioral performance differed by estradiol state, such that the adverse effects of sleep fragmentation on attentional lapses (+â 0.9, trend pâ =â .06) and reaction time (+â 15, pâ <â .05) were observed only when estrogenized. CONCLUSIONS: Menopause-pattern sleep fragmentation and estradiol suppression worsened neurobehavioral performance and daytime sleepiness, even while sleep duration was not reduced. The adverse effects of sleep fragmentation in the context of an adequate sleep duration highlight the importance of sleep continuity as a vital aspect of good sleep health.
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Atenção , Estradiol , Pré-Menopausa , Desempenho Psicomotor , Privação do Sono , Humanos , Feminino , Estradiol/sangue , Privação do Sono/fisiopatologia , Privação do Sono/complicações , Adulto , Pré-Menopausa/fisiologia , Atenção/efeitos dos fármacos , Atenção/fisiologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Sonolência , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
In the process of biological carbon (C) sequestration during reforestation in degraded red soil, due to the decomposition of soil microorganisms, the interaction between soil organic carbon (SOC) and aggregates has an important effect on soil C sequestration. In this study, six common reforestation models and three soil layers were selected in a degraded red soil area of the central subtropical region to determine the composition of soil aggregates and the distribution of SOC in soil aggregates. Based on the results of the soil physicochemical properties and microbial community composition biomass, we assessed the changes in aggregate-associated organic C storage during fluctuations in the stability of the aggregates. After reforestation, the SOC stock increased by 131.28-140.00%. Compared with the three pure forests and broad-leaved mixed forests, coniferous and broad-leaved mixed forests showed the largest proportion of macroaggregates (85.48-89.37%) and higher SOC accumulation. Soil microbial biomass mainly affected the decomposition process of SOC by affecting the stability of the soil aggregates, and the effect of bacteria was more significant. Coniferous and broad-leaved mixed forests can provide more soil microorganisms and C sources than pure forest, thus promoting macroaggregate formation and stability and related organic C storage. This reforestation model has greater C sequestration potential.
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Purpose: Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10-gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism. Methods: The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities. Results: In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel. Conclusion: This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.
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Paclitaxel , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Camundongos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Simulação de Acoplamento Molecular , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Receptores Adrenérgicos beta 2/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Urbanization is one of the important factors leading to biodiversity loss and habitat fragmentation. As an important component of urban ecosystem, soil fauna community plays a key role in improving soil structure and fertility, and promoting material circulation of urban ecosystem. To investigate the distribution characteristics of medium and small-sized soil fauna community in green space and the mechanisms underlying their responses to environmental change during urbanization, we selected 27 green space plots with a gradient of urban, suburban, and rural areas in Nanchang City as study objects, and measured plant parameters, soil physicochemical properties, and distribution characteristics of soil fauna community in these plots. The results showed that a total of 1755 soil fauna individuals were captured, belonging to 2 phyla, 11 classes, and 16 orders. The dominant groups were Collembola, Parasiformes, and Acariformes, which accounting for 81.9% of total soil fauna community. The density, Shannon diversity index, and Simpson dominance index of soil fauna community were significantly higher in suburban area than those in rural area. In the green space of the urban-rural gradient, there were large structure variations in different trophic levels of medium and small-sized soil fauna community. Herbivores and macro-predators occupied the largest proportion in rural area, and less in other areas. Results of the redundancy analysis showed the crown diameter, forest density, soil total phosphorus contents were the main environmental factors affecting soil fauna community distribution, with interpretation rate of 55.9%, 14.0% and 9.7%, respectively. Results of the non-metric multidimensional scale analysis showed that there were variations in soil fauna community characteristics in green space of the urban-rural gradient, and that the aboveground vegetation was the dominant factor for this change. This study improved our understanding of urban ecosystem biodiversity in Nanchang, and provided basis for maintaining soil biodiversity and urban green space construction.
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Ecossistema , Solo , Humanos , Solo/química , Parques Recreativos , Biodiversidade , Urbanização , ChinaRESUMO
Irregular hemorrhagic traumas always threaten the health of patients due to uncontrollable bleeding and wound infections. The traditional hemostatic materials show dissatisfactory hemostatic efficiency and antibacterial activity in solving these potential bleeding dangers. Herein, we proposed a kind of composites based on flexible wood membrane (FWM) loaded with chitosan/alginate derivative for accelerating rapid hemostasis and preventing infection. FWM was removed part of hemicellulose and lignin by using NaOH/Na2SO3 mixture to obtain excellent flexibility while retaining the original porous structure, followed by loading silver nanoparticles on the FWM surface to prepare AgNPs-FWM as an antibacterial bio-carrier. Then, AgNPs-FWM was coated with polyoxyethylene stearate-modified chitosan and multi-aldehyde sodium alginate to fabricate the composites of chitosan/alginate/AgNPs-FWM (CSA/AgNPs-FWM) using in-situ Schiff base reaction. Furthermore, in vitro and in vivo experiments showed that the CSA/AgNPs-FWM composites exhibited lower BCI value (2.6 ± 1.3 %), more rapid hemostasis (26 s) and lower blood loss (67.8 mg) than that of the traditional materials. The possible mechanism for the hemostasis process was not only the high blood absorption capacity, but also the synergistic interaction between hydrophobic alkane chains, amino groups, aldehydes, hydroxyl groups and blood cells. Moreover, CSA/AgNPs-FWM showed exceptional superiorities in mechanical properties and antibacterial activity, which endowed composites high potential in hemostasis application for irregular external wound.
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Quitosana , Hemostáticos , Nanopartículas Metálicas , Alginatos/química , Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Quitosana/farmacologia , Hemostasia , Hemostáticos/farmacologia , Humanos , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , MadeiraRESUMO
Corilagin, a gallotannin, shows excellent antioxidant and anti-inflammatory effects. The NLRP3 inflammasome dysfunction has been implicated in a variety of inflammation diseases. However, it remains unclear how corilagin regulates the NLRP3 inflammasome to relieve gouty arthritis. In this study, bone marrow-derived macrophages (BMDMs) were pretreated with lipopolysaccharide (LPS) and then incubated with NLRP3 inflammasome agonists, such as adenine nucleoside triphosphate (ATP), nigericin, and monosodium urate (MSU) crystals. The MSU crystals were intra-articular injected to induce acute gouty arthritis. Here we showed that corilagin reduced lactate dehydrogenase (LDH) secretion and the proportion of propidium iodide- (PI-)stained cells. Corilagin suppressed the expression of N-terminal of the pyroptosis executive protein gasdermin D (GSDMD-NT). Corilagin restricted caspase-1 p20 and interleukin (IL)-1ß release. Meanwhile, corilagin attenuated ASC oligomerization and speck formation. Our findings confirmed that corilagin diminished NLRP3 inflammasome activation and macrophage pyroptosis. We further discovered that corilagin limited the mitochondrial reactive oxygen species (ROS) production and prevented the interaction between TXNIP and NLRP3, but ROS activator imiquimod could antagonize the inhibitory function of corilagin on NLRP3 inflammasome and macrophage pyroptosis. Additionally, corilagin ameliorated MSU crystals induced joint swelling, inhibited IL-1ß production, and abated macrophage and neutrophil migration into the joint capsule. Collectively, these results demonstrated that corilagin suppressed the ROS/TXNIP/NLRP3 pathway to repress inflammasome activation and pyroptosis and suggest its potential antioxidative role in alleviating NLRP3-dependent gouty arthritis.
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Artrite Gotosa , Piroptose , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/uso terapêutico , Lipopolissacarídeos/farmacologia , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Ácido Úrico/uso terapêutico , Antioxidantes/farmacologia , Nigericina/farmacologia , Nigericina/uso terapêutico , Imiquimode/farmacologia , Imiquimode/uso terapêutico , Propídio/farmacologia , Propídio/uso terapêutico , Nucleosídeos/farmacologia , Caspase 1/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Anti-Inflamatórios/farmacologia , Trifosfato de Adenosina/farmacologia , Adenina/farmacologia , Lactato DesidrogenasesRESUMO
BACKGROUND: Neuroinflammation involving the central nervous system (CNS), such as depression, is associated with a significantly increased risk of cancer and cancer-specific mortality due to breast cancer. It is of great significance to learn about the regulatory process of CNS in breast cancer progression. METHODS: We established a depressive MMTV-PyVT mouse model. The expression levels of neurotransmitters in the serum of depression animal models were assessed by enzyme-linked immunosorbent assay (ELISA). Changes of the microglia cells in the mice's brains were evaluated by immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Breast cancer progression was assessed by immunohistochemistry (IHC) analysis. To further investigate the mechanism by which ant-depressant drugs disrupt breast cancer progression, protein sequencing and network pharmacology were applied to identify related targets. Furthermore, we used conditioned medium from BV-2 microglia to culture breast cancer cells and treated the cells with quercetin at different concentrations; cell viability was assessed by the MTT assay. RESULTS: Our results show a possible regulatory target between neuroinflammation in the CNS and development of breast cancer, along with the reversal effect of quercetin on breast cancer progression. CONCLUSIONS: Chronic stress may be an indicator of breast cancer and that quercetin could be an effective treatment for breast cancer patients with chronic stress.
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ABSTRACT: The present systematic review and meta-analysis was undertaken to evaluate the effects of acupuncture in women with breast cancer (BC), focusing on patient-reported outcomes (PROs). METHODS: A comprehensive literature search was carried out for randomized controlled trials (RCTs) reporting PROs in BC patients with treatment-related symptoms after undergoing acupuncture for at least four weeks. Literature screening, data extraction, and risk bias assessment were independently carried out by two researchers. RESULTS: Out of the 2, 524 identified studies, 29 studies representing 33 articles were included in this meta-analysis. At the end of treatment (EOT), the acupuncture patients' quality of life (QoL) was measured by the QLQ-C30 QoL subscale, the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), the Functional Assessment of Cancer Therapy-General/Breast (FACT-G/B), and the Menopause-Specific Quality of Life Questionnaire (MENQOL), which depicted a significant improvement. The use of acupuncture in BC patients lead to a considerable reduction in the scores of all subscales of the Brief Pain Inventory-Short Form (BPI-SF) and Visual Analog Scale (VAS) measuring pain. Moreover, patients treated with acupuncture were more likely to experience improvements in hot flashes scores, fatigue, sleep disturbance, and anxiety compared to those in the control group, while the improvements in depression were comparable across both groups. Long-term follow-up results were similar to the EOT results. CONCLUSIONS: Current evidence suggests that acupuncture might improve BC treatment-related symptoms measured with PROs including QoL, pain, fatigue, hot flashes, sleep disturbance and anxiety. However, a number of included studies report limited amounts of certain subgroup settings, thus more rigorous, well-designed and larger RCTs are needed to confirm our results.
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Gallic acid is an active phenolic acid widely distributed in plants, and there is compelling evidence to prove its anti-inflammatory effects. NLRP3 inflammasome dysregulation is closely linked to many inflammatory diseases. However, how gallic acid affects the NLRP3 inflammasome remains unclear. Therefore, in the present study, we investigated the mechanisms underlying the effects of gallic acid on the NLRP3 inflammasome and pyroptosis, as well as its effect on gouty arthritis in mice. The results showed that gallic acid inhibited lactate dehydrogenase (LDH) release and pyroptosis in lipopolysaccharide (LPS)-primed and ATP-, nigericin-, or monosodium urate (MSU) crystal-stimulated macrophages. Additionally, gallic acid blocked NLRP3 inflammasome activation and inhibited the subsequent activation of caspase-1 and secretion of IL-1ß. Gallic acid exerted its inhibitory effect by blocking NLRP3-NEK7 interaction and ASC oligomerization, thereby limiting inflammasome assembly. Moreover, gallic acid promoted the expression of nuclear factor E2-related factor 2 (Nrf2) and reduced the production of mitochondrial ROS (mtROS). Importantly, the inhibitory effect of gallic acid could be reversed by treatment with the Nrf2 inhibitor ML385. NRF2 siRNA also abolished the inhibitory effect of gallic acid on IL-1ß secretion. The results further showed that gallic acid could mitigate MSU-induced joint swelling and inhibit IL-1ß and caspase 1 (p20) production in mice. Moreover, gallic acid could moderate MSU-induced macrophages and neutrophils migration into joint synovitis. In summary, we found that gallic acid suppresses ROS generation, thereby limiting NLRP3 inflammasome activation and pyroptosis dependent on Nrf2 signaling, suggesting that gallic acid possesses therapeutic potential for the treatment of gouty arthritis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Gotosa/tratamento farmacológico , Ácido Gálico/uso terapêutico , Inflamassomos/metabolismo , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Piroptose , Transdução de SinaisRESUMO
ABSTRACT This article provides an overview of the intersection of open data and public health by first defining open government data, public health data, and other key concepts and relevant terminologies. There are differing perceptions on the urgency and importance of the openness of public health data. It has been established that disease outbreaks such as happened during the Ebola and Zika virus epidemics are indicative of the need for countries to develop a framework that will provide guidance for the management of public health data. Such a framework should ensure that data collected during public health emergencies are accessible to the appropriate authorities and in a form that can help with timely decision-making during such public health crises. In this article, we highlight available open data policies across many countries, including in the Americas. Our analysis shows that there are currently no articulated policy guidelines for the collection and management of public health data across many countries, especially in Latin America. We propose that any national data governance strategy must address potential benefits, possible risks, examples of data that could be shared, and the attributes of such data. Finally, we stress that the key concern in the Americas should be the development of regional frameworks for open data in public health that can be adopted or adapted by each country through appropriate national or subnational policies and strategies.
RESUMEN Este artículo ofrece un panorama de la intersección entre los datos abiertos y la salud pública al definir en primer lugar qué son los datos gubernamentales abiertos, los datos sobre salud pública y otros conceptos fundamentales y términos pertinentes. Hay percepciones dispares sobre la premura y la importancia de la apertura de los datos sobre salud pública. Se ha establecido que los brotes de ciertas enfermedades, como las epidemias por los virus del Ébola y del Zika, demuestran la necesidad de que los países elaboren un marco que oriente la gestión de los datos sobre salud pública. Dicho marco debe garantizar que los datos recopilados durante las emergencias de salud pública sean accesibles para las autoridades competentes y en una forma que contribuya a la toma oportuna de decisiones durante estas crisis de salud pública. En este artículo, destacamos las políticas de datos abiertos existentes en diversos países, incluidos varios de la Región de las Américas. Nuestro análisis muestra que actualmente en muchos países no hay directrices articuladas de políticas públicas para la recopilación y gestión de los datos sobre salud pública, en especial en América Latina. Proponemos que toda estrategia nacional de gobernanza relativa a los datos debe abordar los posibles riesgos y beneficios, ejemplos de los datos que podrían compartirse y los atributos de tales datos. Por último, subrayamos que el interés fundamental en la Región de las Américas debe ser la creación de marcos regionales para datos abiertos sobre salud pública que cada país pueda adoptar o adaptar mediante las políticas y estrategias nacionales o subnacionales apropiadas.
RESUMO Este artigo expõe um panorama da interseção entre dados abertos e saúde pública, começando por definir o que são dados abertos do governo, dados de saúde pública e outros conceitos fundamentais e terminologias relevantes. Existem distintas percepções quanto à premência e à importância da abertura de dados de saúde pública. Reconhecidamente, os surtos de doenças, como os ocorridos nas epidemias do vírus Ebola e vírus zika, apontam para a necessidade de os países desenvolverem uma estrutura para direcionar o gerenciamento dos dados de saúde pública. Esta estrutura deve servir para garantir que os dados coletados nas emergências de saúde pública estejam acessíveis às autoridades cabíveis em uma forma que possa subsidiar a tomada de decisão oportuna durante tais crises de saúde pública. No artigo, destacam-se as políticas de dados abertos de diversos muitos países, inclusive dos países na Região das Américas. Nossa análise demonstra que vários países, sobretudo na América Latina, não possuem diretrizes claramente definidas de políticas para a coleta e o gerenciamento de dados de saúde pública. Recomendamos que qualquer estratégia nacional de governança de dados nacionais precisa contemplar os possíveis benefícios e riscos, explicitar os dados a ser compartilhados assim como descrever os atributos de tais dados. Por fim, salientamos que a principal preocupação nas Américas deve ser o desenvolvimento de estruturas regionais para dados abertos em saúde pública que possam ser postas em prática ou adaptadas por cada país como parte de estratégias e políticas nacionais ou subnacionais adequadas.