Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of ...quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
It is well accepted that HBx plays the major role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. However, little was known about its role in regulating long noncoding ...RNAs (lncRNAs), a large group of transcripts regulating a variety of biological processes including carcinogenesis in mammalian cells. Here we report that HBx upregulates UCA1 genes and downregulates p27 genes in hepatic LO2 cells. Further studies show that the upregulated UCA1 promotes cell growth by facilitating G1/S transition through CDK2 in both hepatic and hepatoma cells. Knock down of UCA1 in HBx-expressing hepatic and hepatoma cells resulted in markedly increased apoptotic cells by elevating the cleaved caspase-3 and caspase-8. More importantly, UCA1 is found to be physically associated with enhancer of zeste homolog 2 (EZH2), which suppresses p27Kip1 through histone methylation (H3K27me3) on p27Kip1 promoter. We also show that knockdown of UCA1 in hepatoma cells inhibits tumorigenesis in nude mice. In a clinic study, UCA1 is found to be frequently up-regulated in HBx positive group tissues in comparison with the HBx negative group, and exhibits an inverse correlation between UCA1 and p27Kip1 levels. Our findings demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-UCA1/EZH2-p27Kip1 axis, and a potential target of HCC.
Anticancer activities of flavonoids derived from Tephroseris kirilowii (Turcz.) Holub. were evaluated in human cancer cells. We isolated and identified, for the first time, eight flavonoids from T. ...kirilowii and found that three of them (IH: isorhamnetin, GN: genkwanin, and Aca: acacetin) inhibited cell proliferation in a variety of human cancer cell lines. These active flavonoids caused cell cycle arrest at G2/M phase and induced apoptosis and autophagy in human breast cancer cells. Molecular docking revealed that these flavonoids dock in the ATP binding pocket of PI3Kγ. Importantly, treatment with these flavonoids decreased the levels of PI3Kγ-p110, phospho-PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6K, and phospho-ULK. Pretreatment with PI3Kγ specific inhibitor AS605240 potentiated flavonoids-mediated inactivation of AKT, mTOR, p70S6K, ULK, and apoptosis. Taken together, these findings represent a novel mechanism by which downregulation of PI3Kγ-p110 and consequent interruption of PI3K/AKT/mTOR/p70S6K/ULK signaling pathway might play a critical functional role in these flavonoids-induced cell cycle arrest at G2/M phase, apoptosis, and autophagy. Our studies provide novel insights into the anticancer activities of selected flavonoids and their potential uses in anticancer therapy.
An efficient aryl to vinyl 1,4‐palladium migration/Heck sequence was developed for the stereoselective synthesis of 1,3‐dienes. High stereoselectivity was observed not only for 1,3‐dienes bearing two ...similar aryl groups at terminal positions, but also for those with configurations shown to be unfavorable with previous methods.
1,4 all: An efficient aryl to vinyl 1,4‐palladium/Heck sequence has been developed for the stereoselective synthesis of 1,3‐dienes. High stereoselectivity was observed not only for 1,3‐dienes bearing two similar aryl groups at terminal positions, but also for those with configurations shown to be unfavorable with previous methods.
CBP60b (CALMODULIN-BINDING PROTEIN 60b) is a member of the CBP60 transcription factor family. In Arabidopsis, AtCBP60b not only regulates growth and development but also activates the transcriptions ...in immune responses. So far, CBP60b has only been studied extensively in the model plant Arabidopsis and rarely in crops. In this study, Bean pod mottle virus (BPMV)-mediated gene silencing (BPMV-VIGS) was used to silence GmCBP60b.1/2 in soybean plants. The silencing of GmCBP60b.1/2 resulted in typical autoimmunity, such as dwarfism and enhanced resistance to both Soybean mosaic virus (SMV) and Pseudomonas syringae pv. glycinea (Psg). To further understand the roles of GmCBP60b in immunity and circumvent the recalcitrance of soybean transformation, we generated transgenic tobacco lines that overexpress GmCBP60b.1. The overexpression of GmCBP60b.1 also resulted in autoimmunity, including spontaneous cell death on the leaves, highly induced expression of PATHOGENESIS-RELATED (PR) genes, significantly elevated accumulation of defense hormone salicylic acid (SA), and significantly enhanced resistance to Pst DC3000 (Pseudomonas syrangae pv. tomato DC3000). The transient coexpression of a luciferase reporter gene driven by the promoter of soybean SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (GmSARD1) (ProGmSARD1::LUC), together with GmCBP60b.1 driven by the 35S promoter, led to the activation of the LUC reporter gene, suggesting that GmCBP60b.1 could bind to the core (A/T)AATT motifs within the promoter region of GmSARD1 and, thus, activate the expression of the LUC reporter. Taken together, our results indicate that GmCBP60b.1/2 play both positive and negative regulatory roles in immune responses. These results also suggest that the function of CBP60b is conserved across plant species.
Newcastle disease (ND) is one of the most economically devastating infectious diseases affecting the poultry industry. Virulent Newcastle disease virus (NDV) can cause high mortality and severe ...tissue lesions in the respiratory, gastrointestinal, neurological, reproductive and immune systems of poultry. Tremendous progress has been made in preventing morbidity and mortality caused by ND based on strict biosecurity and wide vaccine application. In recent decades, the continual evolution of NDV has resulted in a total of twenty genotypes, and genetic variation may be associated with disease outbreaks in vaccinated chickens. In some countries, the administration of genotype-matched novel vaccines in poultry successfully suppresses the circulation of virulent NDV strains in the field. However, virulent NDV is still endemic in many regions of the world, especially in low- and middle-income countries, impacting the livelihood of millions of people dependent on poultry for food. In ND-endemic countries, although vaccination is implemented for disease control, the lack of genotype-matched vaccines that can reduce virus infection and transmission as well as the inadequate administration of vaccines in the field undermines the effectiveness of vaccination. Dissection of the profiles of existing ND vaccines is fundamental for establishing proper vaccination regimes and developing next-generation vaccines. Therefore, in this article, we provide a broad review of commercial and experimental ND vaccines and promising new platforms for the development of next-generation vaccines.
Mitochondria fission and mitophagy are fundamentally crucial to cellular physiology and play important roles in cancer progression. Developing a comprehensive understanding of the molecular mechanism ...underlying mitochondrial fission and mitophagy will provide novel strategies for cancer prevention and treatment. Actin has been shown to participate in mitochondrial fission and mitophagy regulation. Cofilin is best known as an actin-depolymerizing factor. However, the molecular mechanism by which cofilin regulates mitochondrial fission and mitophagy remains largely unknown. Here we report that knockdown of cofilin attenuates and overexpression of cofilin potentiates mitochondrial fission as well as PINK1/PARK2-dependent mitophagy induced by staurosporine (STS), etoposide (ETO), and carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Cofilin-mediated-PINK1 (PTEN-induced putative kinase 1) accumulation mainly depends on its regulation of mitochondrial proteases, including peptidase mitochondrial processing beta (MPPβ), presenilin-associated rhomboid-like protease (PARL), and ATPase family gene 3-like 2 (AFG3L2), via mitochondrial membrane potential activity. We also found that the interaction and colocalization of G-actin/F-actin with cofilin at mitochondrial fission sites undergo constriction after CCCP treatment. Pretreatment with the actin polymerization inhibitor latrunculin B (LatB) increased and actin-depolymerization inhibitor jasplakinolide (Jas) decreased mitochondrial translocation of actin induced by STS, ETO, and CCCP. Both LatB and Jas abrogated CCCP-mediated mitochondrial fission and mitophagy. Our data suggest that G-actin is the actin form that is translocated to mitochondria, and the actin-depolymerization activity regulated by cofilin at the mitochondrial fission site is crucial for inducing mitochondrial fission and mitophagy.
Detecting various anomalies using optical satellite data prior to strong earthquakes is key to understanding and forecasting earthquake activities because of its recognition of ...thermal-radiation-related phenomena in seismic preparation phases. Data from satellite observations serve as a powerful tool in monitoring earthquake preparation areas at a global scale and in a nearly real-time manner. Over the past several decades, many new different data sources have been utilized in this field, and progressive anomaly detection approaches have been developed. This paper reviews the progress and development of pre-seismic anomaly detection technology in this decade. First, precursor parameters, including parameters from the top of the atmosphere, in the atmosphere, and on the Earth's surface, are stated and discussed. Second, different anomaly detection methods, which are used to extract anomalous signals that probably indicate future seismic events, are presented. Finally, certain critical problems with the current research are highlighted, and new developing trends and perspectives for future work are discussed. The development of Earth observation satellites and anomaly detection algorithms can enrich available information sources, provide advanced tools for multilevel earthquake monitoring, and improve short- and medium-term forecasting, which play a large and growing role in pre-seismic anomaly detection research.
•New SLR retrieval model was developed for hyperspectral infrared sounders.•An AIRS footprint geometrical model was proposed to match MODIS cloud masks.•Site spatial representativeness was important ...for validating low resolution products.•The SLR model was insensitive to AIRS instrument noise.•Significant diurnal variation of retrieval errors should be considered.
Surface longwave radiation (SLR) derived from remotely sensed data facilitates understanding of the SLR in global climate change. Hyperspectral infrared sounders aboard space platforms provide information on the surface and vertical structure of Earth’s atmosphere. However, currently, SLR products estimated from these observations are unavailable, which hampers their application potential for Earth’s radiation budget in the context of global warming. To address this issue, we developed simple and effective SLR model under clear-sky conditions using at-sensor spectral radiances from Atmospheric Infrared Sounder (AIRS). The model was found to be insensitive to AIRS instrument noise, and showed good performances based on a simulation dataset. The AIRS footprint geometrical model was proposed to match the AIRS and Moderate Resolution Imaging Spectroradiometer (MODIS) data to estimate the cloud fraction. Validation against ground-based measurements found that the surface upward longwave radiation model has a bias of 3.18 W/m2, root-mean-square error (RMSE) of 30.51 W/m2, and R2 of 0.84; the surface downward longwave radiation model has a bias of 0.77 W/m2, RMSE of 29.09 W/m2, and R2 of 0.78. The large validation biases at two ground sites reflect the limited spatial representativeness for AIRS footprints. Terrain-induced altitude differences and spatial inhomogeneity can redistribute the spatial distributions of SLR. Moreover, the model performances were weakly dependent on seasonal variation. The results indicate that the proposed model provides a foundation for the further development of operational SLR products.
High mobility group box 1 (HMGB1) is a ubiquitous and highly conserved non-histone DNA-binding protein with different biological functions according to its subcellular localization. It is widely ...believed that HMGB1, which is released into the extracellular space, plays a key role in the inflammatory response. In recent years, numerous studies have shown that the development of various neurological diseases such as epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), cerebrovascular disease and traumatic brain injury (TBI) are inextricably linked to inflammation. We will review the mechanisms of HMGB1 and its receptors in nervous system inflammation to provide a basis for further development of new HMGB1-based therapies.
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•HMGB1 is a potential biomarker of human neuroinflammatory diseases.•HMGB1 mediates neuroinflammatory response mainly by binding to TLR4 and RAGE.•The intervention of HMGB1 expression can inhibit the development of various neuroinflammatory related diseases.
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