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1.
J Nanobiotechnology ; 19(1): 54, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627152

RESUMO

BACKGROUND: Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine. RESULTS: In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group. CONCLUSIONS: The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.

2.
EMBO Rep ; : e51298, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33594776

RESUMO

Notch signaling and epigenetic factors are known to play critical roles in regulating tissue homeostasis in most multicellular organisms, but how Notch signaling coordinates with epigenetic modulators to control differentiation remains poorly understood. Here, we identify heterochromatin protein 1c (HP1c) as an essential epigenetic regulator of gut homeostasis in Drosophila. Specifically, we observe that HP1c loss-of-function phenotypes resemble those observed after Notch signaling perturbation and that HP1c interacts genetically with components of the Notch pathway. HP1c represses the transcription of Notch target genes by directly interacting with Suppressor of Hairless (Su(H)), the key transcription factor of Notch signaling. Moreover, phenotypes caused by depletion of HP1c in Drosophila can be rescued by expressing human HP1γ, suggesting that HP1γ functions similar to HP1c in Drosophila. Taken together, our findings reveal an essential role of HP1c in normal development and gut homeostasis by suppressing Notch signaling.

3.
Int J Biol Macromol ; 172: 573-579, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33454335

RESUMO

In this study, a simple strategy to fabricate the cellulose aerogel with homogeneous porous structure and good compression strength properties has been demonstrated. The cellulose aerogel was simply prepared by adding styrene acrylic emulsion (SAE) to the TEMPO-oxidized cellulose nanofibrils (CNF), followed by freeze-drying and oven-heating, in which covalent bond between CNF and SAE was confirmed by FT-IR. Meanwhile, the regulation process of porous structure of cellulose aerogels was investigated by varying the properties of CNF, and the addition of carboxymethyl cellulose (CMC) and SAE. The results demonstrated that the porous structure of cellulose aerogel was gradually improved with increasing carboxyl content of CNF. CMC could effectively increase in specific surface area of cellulose aerogel, achieving a more preferred porous structure due to the elimination of hornification. SAE could highly enhance the uniformity of structure with specific surface area up to 184 m2/g, porosity up to 99%, and successfully improve the strength properties, showing the fabricated cellulose aerogel as a potential cushion packaging material.

4.
Brief Bioinform ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33415333

RESUMO

Predicting disease-related long non-coding RNAs (lncRNAs) is beneficial to finding of new biomarkers for prevention, diagnosis and treatment of complex human diseases. In this paper, we proposed a machine learning techniques-based classification approach to identify disease-related lncRNAs by graph auto-encoder (GAE) and random forest (RF) (GAERF). First, we combined the relationship of lncRNA, miRNA and disease into a heterogeneous network. Then, low-dimensional representation vectors of nodes were learned from the network by GAE, which reduce the dimension and heterogeneity of biological data. Taking these feature vectors as input, we trained a RF classifier to predict new lncRNA-disease associations (LDAs). Related experiment results show that the proposed method for the representation of lncRNA-disease characterizes them accurately. GAERF achieves superior performance owing to the ensemble learning method, outperforming other methods significantly. Moreover, case studies further demonstrated that GAERF is an effective method to predict LDAs.

5.
Chemosphere ; 262: 127901, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805660

RESUMO

In this work, Lysinibacillus sp. JLT12 was used to remove the Cr(VI)-induced passive layer on the magnetite. Mechanism study via dynamic kinetics, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy analyses revealed that Lysinibacillus sp. JLT12 could remove the passive layer (lepidocrocite and goethite) to facilitate the further Cr(VI) reduction by magnetite. For large-scale applications, porous ceramsite (PC) was prepared with magnetite, kaolin, and fallen leaves. Lysinibacillus sp. was then immobilized on the holes in PC. Slow-released nutrients were added to immobilized porous ceramsite (IM-PC) at a ratio of 1.5:10 (g/g) to supply carbon, nitrogen, and phosphorus to Lysinibacillus sp. JLT12 with low secondary pollution. The performance of IM-PC was evaluated via a column experiment. The results indicate that, in the presence of Lysinibacillus, the break-through time and maximum adsorption ability of IM-PC were 11.67 h and 121.47 mg/g, respectively. These values are higher than those of PC. Additionally, break-through curves detected at 5, 10, and 15 days demonstrated that the usage life of IM-PC was significantly longer than that of PC.


Assuntos
Cromo/química , Óxido Ferroso-Férrico/química , Poluentes Químicos da Água/química , Adsorção , Bacillus , Biodegradação Ambiental , Carbono , Cromo/análise , Compostos Férricos , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia Fotoeletrônica , Poluentes Químicos da Água/análise , Difração de Raios X
6.
Molecules ; 25(23)2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33276431

RESUMO

Phytochemistry investigations on Ailanthus altissima (Mill.) Swingle, a Simaroubaceae plant that is recognized as a traditional herbal medicine, have afforded various natural products, among which C20 quassinoid is the most attractive for their significant and diverse pharmacological and biological activities. Our continuous study has led to the isolation of two novel quassinoid glycosides, named chuglycosides J and K, together with fourteen known lignans from the samara of A. altissima. The new structures were elucidated based on comprehensive spectra data analysis. All of the compounds were evaluated for their anti-tobacco mosaic virus activity, among which chuglycosides J and K exhibited inhibitory effects against the virus multiplication with half maximal inhibitory concentration (IC50) values of 56.21 ± 1.86 and 137.74 ± 3.57 µM, respectively.

7.
Front Pharmacol ; 11: 533809, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071778

RESUMO

Podocyte apoptosis is the common pathological basis for the progression of various kidney diseases. The overexpression of NOX4, a key enzyme involved in oxidative stress, has been proved to participate in the occurrence of podocyte apoptosis. Autophagy is a kind of adaptive response of cells under stress. However, as a "double-edged sword", the effect of autophagy on apoptosis in different cells and conditions is complex and variable, which has not been fully explained yet. Morroniside, extracted from the traditional medicinal plant Cornus officinalis, has remarkable antioxidant and anti-apoptosis effects, and has been proven to inhibit the overexpression of NOX4 in kidney tissue. Therefore, H2O2 was used in this study to explore the effects of autophagy on podocyte NOX4 overexpression and apoptosis induced by oxidative stress, as well as the protection mechanism of morroniside in podocytes. The results showed that the autophagy activator rapamycin, as well as the autophagy inhibitor chloroquine, could induce podocyte apoptosis cultured in normal condition, and chloroquine could also significantly increase the NOX4 expression. The NOX4 expression and apoptosis rate of podocytes increased after H2O2 treatment, the expression of LC3-II decreased, and the expressions of p62, mTOR, and p-mTOR increased. The intervention of morroniside and rapamycin improved autophagy activity and inhibited NOX4 overexpression and apoptosis induced by H2O2. And chloroquine reversed the inhibitory effect of morroniside on NOX4 overexpression and podocyte apoptosis. Taken together, our results suggest that the expression level of NOX4 in podocytes is regulated by autophagy activity. Morroniside can reduce oxidative stress induced podocyte apoptosis by restoring the damaged autophagy flux and inhibit the overexpression of NOX4.

8.
Liver Cancer ; 9(5): 563-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33083281

RESUMO

Background: Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. Aims: The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. Methods: The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. Results: The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. Conclusions: The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.

9.
Front Pharmacol ; 11: 01067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041782

RESUMO

Matrine (MT) is a naturally occurring alkaloid and an bioactive component of Chinese herbs, such as Sophora flavescens and Radix Sophorae tonkinensis. Emerging evidence suggests that MT possesses anti-cancer, anti-inflammatory, anti-oxidant, antiviral, antimicrobial, anti-fibrotic, anti-allergic, antinociceptive, hepatoprotective, cardioprotective, and neuroprotective properties. These pharmacological properties form the foundation for its application in the treatment of various diseases, such as multiple types of cancers, hepatitis, skin diseases, allergic asthma, diabetic cardiomyopathy, pain, Alzheimer's disease (AD), Parkinson's disease (PD), and central nervous system (CNS) inflammation. However, an increasing number of published studies indicate that MT has serious adverse effects, the most obvious being liver toxicity and neurotoxicity, which are major factors limiting its clinical use. Pharmacokinetic studies have shown that MT has low oral bioavailability and short half-life in vivo. This review summarizes the latest advances in research on the pharmacology, toxicology, and pharmacokinetics of MT, with a focus on its biological properties and mechanism of action. The review provides insight into the future of research on traditional Chinese medicine.

10.
ACS Appl Mater Interfaces ; 12(43): 48861-48873, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33059441

RESUMO

Obtaining a perovskite light-absorbing layer with good crystallization, low defect concentration, good stability, and well-matched energy levels is critical to obtaining high-efficiency perovskite solar cells (PSCs). Here, a hybrid PSC with a graded band gap is explored using MAPbBr3 (MA = CH3NH3) and MAPbBr0.9I2.1 quantum dots (QDs) as component cells. We have creatively designed a solar cell device with a double-QD structure [indium tin oxide (ITO)/SnO2/perovskite:MAPbBr3 QDs/MAPbBr0.9I2.1 QDs/Spiro-OMeTAD/Au]. A better crystal film of the perovskite absorption layer can be obtained because the MAPbBr3 QDs are doped in an antisolvent, which induces nucleation and growth in the polycrystalline perovskite. In addition, we expect that digestive ripening occurred in the crystallization, and the oleic acid ligands on the surface of the QDs disintegrate during the doping process and transfer to the surface of the perovskite absorption layer finally; it follows that the hydrophobicity and stability of the perovskite film are greatly enhanced. Moreover, a thin film of MAPbBr0.9I2.1 QDs is introduced between the perovskite absorption layer and the hole layer, acting as an energy-level ladder, which leads to well-matched energy levels, an increase in fill factor (FF), and an enhanced hole transport capability. In particular, the mechanism of the crystallization process involving the effect of oleic acid ligands on the interior and surface of the perovskite film is fully discussed here. The final research results from the PSCs show that both high efficiency and long-term stability are achieved successfully by this design strategy.

11.
G3 (Bethesda) ; 10(12): 4483-4488, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33020192

RESUMO

The flySAM/CRISPRa system has recently emerged as a powerful tool for gain-of-function studies in Drosophila melanogaster This system includes Gal4/UAS-driven dCas9 activators and U6 promoter-controlled sgRNA. Having established dCas9 activators superior to other combinations, to further enhance the efficiency of the targeting activators we systematically optimized the parameters of the sgRNA. Interestingly, the most efficient sgRNAs were found to accumulate in the region from -150bp to -450bp upstream of the transcription start site (TSS), and the activation efficiency showed a strong positive correlation with the GC content of the sgRNA targeting sequence. In addition, the target region is dominant to the GC content, as sgRNAs targeting areas beyond -600bp from the TSS lose efficiency even when containing 75% GC. Surprisingly, when comparing the activities of sgRNAs targeting to either DNA strand, sgRNAs targeting to the non-template strand outperform those complementary to the template strand, both in cells and in vivo In summary, we define criteria for sgRNA design which will greatly facilitate the application of CRISPRa in gain-of-function studies.

12.
Drug Discov Today ; 25(12): 2080-2088, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33017690

RESUMO

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

13.
Front Genet ; 11: 572983, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101392

RESUMO

Non-coding RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be indispensable factors in carcinogenesis and cancer development. Numerous studies have explored the regulatory functions of these molecules and identified the synergistic interactions among lncRNAs or miRNAs, while those between lncRNAs and miRNAs remain to be investigated. In this study, we constructed and characterized an lncRNA-miRNA synergistic network following a four-step approach by integrating the regulatory pairs and expression profiles. The synergistic interactions with more shared regulatory mRNAs were found to have higher interactional intensity. Through the analysis of nodes in the network, we found that lncRNAs played roles that are more central and had similar synergistic interactions with their neighbors when compared with miRNAs. In addition, known colon adenocarcinoma (COAD)-related RNAs were found to be enriched in this synergistic network, with higher degrees, betweenness, and closeness. Finally, we proposed a risk score model to predict the clinical outcome for COAD patients based on two prognostic hub lncRNAs, MEG3 and ZEB1-AS1. Moreover, the hierarchical networks of these two lncRNAs could contribute to the understanding of the biological mechanism of tumorigenesis. For each lncRNA-miRNA interaction in the hub-related subnetwork and two hierarchical networks, we performed RNAup method to evaluate their binding energy. Our results identified two important lncRNAs with prognostic roles in colon cancer and dissected their regulatory mechanism involving synergistic interaction with miRNAs.

14.
Oxid Med Cell Longev ; 2020: 2684672, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101585

RESUMO

Oxidative stress-induced dysfunction or apoptosis in retinal pigment epithelial (RPE) cells is an important cause of dry age-related macular degeneration (AMD). Although phillyrin has been shown to exert significant antioxidant effects, the underlying mechanism of action remains unclear. The purpose of this study was to investigate the protective effect of phillyrin on hydrogen peroxide- (H2O2-) induced oxidative stress damage in RPE cells and the potential mechanism involved. It was found that phillyrin significantly protected RPE cells from H2O2 cytotoxicity. Furthermore, phillyrin alleviated oxidative stress-induced apoptosis via inhibition of endogenous and exogenous apoptotic pathways. Compared with the H2O2-treated group, the expressions of cleaved caspase-3, cleaved caspase-9, cleaved polymerase (PARP), death receptor Fas, and cleaved caspase-8, as well as Bax/Bcl-2 ratio were decreased in RPE cells after the phillyrin intervention. In addition, phillyrin reversed the oxidative stress-induced reductions in superoxide dismutase (SOD) and glutathione (GSH) levels and annulled the elevations in reactive oxygen species (ROS) and malondialdehyde (MDA), thereby restoring oxidant-antioxidant homeostasis. Phillyrin treatment upregulated the expressions of cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin A and downregulated the expressions of p21 and p-p53, thereby reversing the G0/G1 cell cycle arrest in H2O2-treated RPE cells. Pretreatment with phillyrin also increased the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), total Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductases-1 (NQO-1) in RPE cells and inhibited the formation of Kelch-like ECH-associated protein 1 (Keap1)/Nrf2 protein complex. Thus, phillyrin effectively protected RPE cells from oxidative stress through activation of the Nrf2 signaling pathway and inhibition of the mitochondria-dependent apoptosis pathway.

15.
Environ Toxicol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996673

RESUMO

Carbon tetrachloride (CCl4 ) exposure can induce hepatic ductular reactions. To date, however, the related mechanism remains largely unknown. Sonic hedgehog (Shh) and Yes-associated protein (Yap) signaling are correlated with liver injury and regeneration. Herein, we investigated the role of Shh and Yap signaling in the fate of ductular reaction cells in CCl4 -treated livers and the possible mechanisms. Wild-type and Shh-EGFP-Cre male mice were exposed to CCl4 (2 mL/kg), and then treated with or without the Shh signaling inhibitor Gant61. The level of liver injury, proliferation of ductular reaction cells, and expression levels of mRNA and protein related to the Shh and Yap signaling components were assessed. Results showed that CCl4 treatment induced liver injury and promoted activation and proliferation of ductular reaction cells. In addition, CCl4 induced the expression of Shh ligands in hepatocytes, accompanied by activation of Shh and Yap1 signaling in the liver. Furthermore, administration of Gant61 ameliorated liver regeneration, inhibited hepatic ductular reactions, and decreased Shh and Yap1 signaling activity. Thus, Shh-Yap1 signaling appears to play an integral role in the proliferation of ductular reaction cells in CCl4 -induced liver injury. This study should improve our understanding of the mechanism of CCl4 -induced liver injury and ductular reactions and provide support for future investigations on liver disease therapy.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32991287

RESUMO

Numerous studies have shown that microRNAs are associated with the occurrence and development of human diseases. Thus, studying disease-associated miRNAs is significantly valuable to the prevention, diagnosis and treatment of diseases. In this paper, we proposed a novel method based on matrix completion and non-negative matrix factorization (MCNMF) for predicting disease-associated miRNAs. Due to the information inadequacy on miRNA similarities and disease similarities, we calculated the latter via two models, and introduced the Gaussian interaction profile kernel similarity. In addition, the matrix completion (MC) was employed to further replenish the miRNA and disease similarities to improve the prediction performance. And to reduce the sparsity of miRNA-disease association matrix, the method of weighted K nearest neighbor (WKNKN) was used, which is a pre-processing step. We also utilized non-negative matrix factorization (NMF) using dual L2,1-norm, graph Laplacian regularization, and Tikhonov regularization to effectively avoid the overfitting during the prediction. Finally, several experiments and a case study were implemented to evaluate the effectiveness and performance of the proposed MCNMF model. The results indicated that our method could reliably and effectively predict disease-associated miRNAs.

17.
Pharm Biol ; 58(1): 950-958, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32956595

RESUMO

CONTEXT: Acetylshikonin, a naphthoquinone derivative, is mainly extracted from some species of the family Boraginaceae, such as Lithospermum erythrorhizon Sieb. et Zucc., Arnebia euchroma (Royle) Johnst., and Arnebia guttata Bunge. As a bioactive compound, acetylshikonin has attracted much attention because of its broad pharmacological properties. OBJECTIVE: This review provides a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of acetylshikonin focussing on its mechanisms on the basis of currently available literature. METHODS: The information of acetylshikonin from 1977 to 2020 was collected using major databases including Elsevier, Scholar, PubMed, Springer, Web of Science, and CNKI. Acetylshikonin, pharmacology, toxicity, pharmacokinetics, and naphthoquinone derivative were used as key words. RESULTS: According to emerging evidence, acetylshikonin exerts a wide spectrum of pharmacological effects such as anticancer, anti-inflammatory, lipid-regulatory, antidiabetic, antibacterial, antifungal, antioxidative, neuroprotective, and antiviral properties. However, only a few studies have reported the adverse effects of acetylshikonin, with respect to reproductive toxicity and genotoxicity. Pharmacokinetic studies demonstrate that acetylshikonin is associated with a wide distribution and poor absorption. CONCLUSIONS: Although experimental data supports the beneficial effects of this compound, acetylshikonin cannot be considered as a therapy drug without further investigations, especially, on the toxicity and pharmacokinetics.

18.
Chem Biodivers ; 17(11): e2000553, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32939973

RESUMO

Toona sinensis (A.Juss.) M.Roem., a multi-purpose tree of Meliaceae, is widely distributed and intensively cultivated in Asia, yet its high yielding, lipid-rich seeds are rarely exploited. The present study systematically analyzed the differences and correlations of seed morphological characteristics and fatty acid (FA) profiles of 62 representative T. sinensis germplasms distributed across northern to southern China. T. sinensis seeds were rich in total FAs (TFA, 107.03-176.18 mg/g). Additionally, linoleic acid (54.69-100.59 mg/g), α-linolenic acid (ALA, 22.47-45.02 mg/g), oleic acid (OA, 5.12-23.94 mg/g), palmitic acid (6.87-14.14 mg/g), stearic acid (SA, 3.13-6.57 mg/g) and elaidic acid (1.70-2.88 mg/g) were the major FAs measured by GC/MS analysis. Size (average width of 3.94±0.01 mm and length of 5.79±0.02 mm) and mass (average thousand-seed weight of 10.52±0.17 g) were greater in T. sinensis seeds collected south than north of 30° latitude. These traits were also positively correlated with unsaturated FA content and negatively related to SA and saturated FA contents (P<0.05). Significant positive correlations were found between seed length and polyunsaturated FA (R2 =0.370) and ALA levels (R2 =0.296), as well as between thousand-seed weight and monounsaturated FAs (R2 =0.309) and OA levels (R2 =0.297) (P<0.05). Seventeen T. sinensis germplasms gathered by cluster analysis as cluster IV were determined as desirable for oil processing due to their higher TFA and ALA contents and greater seed size and mass than others. Generally, the wider, heavier, and especially longer seeds of T. sinensis contain much higher levels of FAs, especially ALA, and are the more promising sources for breeding and the oil processing industry.

19.
Biomed Pharmacother ; 131: 110661, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32942154

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers with the highest morbidity and mortality. It is necessary to develop new anti-liver cancer drugs. Itraconazole is a popular systemic anti-fungal drug with a strong anti-tumor effect. However, so far, it is not clear whether itraconazole has specific anti-tumor effect on liver cancer. The purpose of this study was to investigate itraconazole resistant effect of liver cancer and to explore its potential anti-cancer mechanism. The effect of itraconazole on the proliferation of liver cancer cells was studied with MTT assay. Flow cytometry was used to determine the effect of itraconazole on apoptosis, cell cycle distribution, changes in intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). In addition, after DAPI staining, nuclear morphological changes were observed under the fluorescent microscope, and the release of lactate dehydrogenase (LDH) was measured using the microplate reader. Finally, the expressions of proteins related to the anti-tumor signaling pathway were determined by Western blotting. The results showed that itraconazole significantly inhibited the proliferation of HepG2 and Bel-7405 cells. In addition, the data showed that itraconazole induced apoptosis in HepG2 cells, increased the production of ROS, blocked cell cycle, and decreased MMP. Furthermore, itraconazole inhibited HCC cell growth and promoted apoptosis through the Hh, Wnt/catenin, AKT/mTOR/S6K, ROS and death receptor pathways. Finally, we come to the conclusion that itraconazole exerts anti-liver cancer effect, and has potential for use as a new drug for liver cancer in clinic.

20.
Biomed Pharmacother ; 131: 110750, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32942160

RESUMO

Rhizoma Paris is a popular Chinese medicine in clinics. It contains four main saponins which are its major bioactive compounds. These saponins are Paris saponin I, II, VI and VII (PSI, PSII, PSVI and PSVII, respectively). Up to now, the research using HUVEC cells to evaluate the anti-angiogenic activity of four saponins is blank. The purpose of this study was to evaluate the anti-angiogenic properties (also known as angiotoxicity) of the four saponins in Rhizoma Paris on vascular endothelial cells-HUVEC cells, and to investigate the underlying mechanism, which has not been studied before. In this study, MTT assay, Lactate dehydrogenase (LDH) assay, wound healing experiments, transwell cell invasion assay, tubule formation experiment, DAPI staining, AV-PI double staining, and cell cycle analysis were used to determine the effects of Paris saponins. The results showed that, with increases in concentrations of PSI, PSII, PSVI and PSVII, the viability of HUVEC cells decreased significantly. In addition, four saponins dose-dependent enhanced LDH release and inhibited HUVEC cell migration, invasion, and angiogenesis. In terms of mechanism, PSI significantly inhibited protein expression in multiple signaling pathways. In particular, with the VEGF2 as the target, it activate the downstream PI3K / AKT / mTOR, SRC / eNOS, P38, PLCγ / ERK / MERK and JAK2/STAT3 signaling pathways. In conclusion, PSI, PSII, PSVI and PSVII can inhibit endothelial cell proliferation, migration and invasion, block endothelial cell cycle, induce endothelial cell apoptosis, act on protein expression in several anti-angiogenic signaling pathways, and finally inhibit angiogenesis in vitro. This study provides further data support for the clinical application of Paris saponins as antiangiogenic drugs.

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