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1.
Chem Sci ; 12(44): 14883-14892, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34820104

RESUMO

Ustilaginoidins are a type of mycotoxin featuring a dimeric naphtho-γ-pyrone skeleton, produced by the rice false smut pathogen Ustilaginoidea virens. Here we used gene disruption, heterologous expression in Aspergillus oryzae, feeding experiments, and in vitro experiments to fully elucidate the biosynthesis of ustilaginoidins. A new route to dimeric 2,3-unsaturated naphtho-γ-pyrones via dimerization of YWA1 (and 3-methyl YWA1) followed by dehydration was discovered. Intriguingly, the reduction of the 2,3-double bond of the pyrenone ring was catalyzed by a phospholipid methyltransferase-like enzyme (UsgR). The reductase was specific for reduction of monomeric, linear naphtho-γ-pyrenones, but not for the dimers. Atroposelective coupling of various monomers by the laccase (UsgL) led to diverse ustilaginoidins. Moreover, 3-epimerism of the 3-methyl-2,3-dihydro-naphtho-γ-pyrones adds additional complexity to the biosynthesis.

2.
Plant Physiol Biochem ; 169: 224-235, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34808465

RESUMO

Basic/helix-loop-helix (bHLH) transcription factors are involved in various metabolic and physiological processes in plants. Sweetpotato (Ipomoea batatas (L.) Lam.) is an important crop in China but is highly susceptible to cold stress. However, little information on the bHLH gene family is available, and the function of this family in response to cold stress has not been revealed in sweetpotato. Here, 110 IbbHLHs were identified and classified into 17 categories based on phylogenetic relationships, conserved motifs and gene structure analyses. Except for 5 IbbHLHs, 90 IbbHLHs were putative E-box-binding proteins including 70 IbbHLHs belonging to G-box, whereas 15 IbbHLHs were putative non-E box-binding proteins based on DNA-binding analysis. In total, 37 pairs of segmental duplicated genes and 5 pairs of tandem duplication genes were identified within the IbbHLH gene family. The transcript level of 20 IbbHLHs was regulated by cold stress based on RNA-seq data, and 8 genes were selected for further quantitative real-time PCR (qRT-PCR) analysis. IbHLH8 and IbHLH92 are involved in network interaction with several genes related to abiotic and biotic stresses under cold treatment. IbbHLH79, an ICE1-like gene, was isolated and overexpressed in sweetpotato. The IbbHLH79 protein can activate the CBF (C-repeat Binding Factor) pathway, and IbbHLH79-overexpressing transgenic plants display enhanced cold tolerance. Taken together, these results provide valuable information on the IbbHLH gene family; in addition, several IbbHLHs may regulate cold stress, and the results suggest IbbHLH79 will be useful for molecular breeding of enhanced cold tolerance in sweetpotato.

3.
J Exp Clin Cancer Res ; 40(1): 351, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749766

RESUMO

BACKGROUND: Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gastric cancer progression. METHODS: The expression of LINC01050 in the context of gastric cancer was assessed using The Cancer Genome Atlas datasets. Its functions in gastric cancer were investigated through gain- and loss-of-function experiments combined with the Cell Counting Kit-8 assays, colony-forming assays, Transwell assays, flow cytometry, Western blot analyses, and xenograft tumor and mouse metastasis models. Potential LINC01050 transcription activators were screened via bioinformatics and validated by chromatin immunoprecipitation and luciferase assays. The interaction between LINC01050 and miR-7161-3p and the targets of miR-7161-3p were predicted by bioinformatics analysis and confirmed by a luciferase assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments. RESULTS: LINC01050 was significantly up-regulated in gastric cancer, and its high expression was positively correlated with a poor prognosis. The transcription factor c-Myc was found to directly bind to the LINC01050 promoter region and activate its transcription. Furthermore, overexpression of LINC01050 was confirmed to promote gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. At the same time, its knockdown inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro along with tumor growth and metastasis in vivo. Moreover, mechanistic investigations revealed that LINC01050 functions as a molecular sponge to absorb cytosolic miR-7161-3p, which reduces the miR-7161-3p-mediated translational repression of SPZ1, thus contributing to gastric cancer progression. CONCLUSIONS: Taken together, our results identified a novel gastric cancer-associated lncRNA, LINC01050, which is activated by c-Myc. LINC01050 may be considered a potential therapeutic target for gastric cancer.

4.
Chem Asian J ; 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34658163

RESUMO

The generation of free radicals is a key process in the formation and the collapse of the bubbles in water, however, the direct and dynamic observation of the radicals in this process at single bubbles has never been achieved. Here, the hydroxyl (OH. ) and oxygen (O2 .- ) radicals at single oxygen bubbles are continuously traced using chemiluminescence (CL), in which these radicals at the bubble react with the surrounding luminol in the solution emitting the light. Varied increase trends of luminescence are observed in the generation of a bubble, floating, short parking at the water/air interface and the final explosion, revealing the complexity in the distribution of radicals at the bubble unprecedentedly. Despite more radicals are observed at the bubble generated at a deep position under the water for the stabilization, almost the same amount of radicals are included in the bubbles that is independent on the water pressure during the production of the bubble. This rich information collected from the dynamic study of bubbles illustrates the complicated generation and distribution process of radicals at the bubbles, and will facilitate the understanding of the function about the bubbles.

5.
APL Bioeng ; 5(4): 041502, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34632251

RESUMO

Despite diagnostic and therapeutic advances, liver cancer kills more than 18 million people every year worldwide, urging new strategies to model the disease and to improve the current therapeutic options. In vitro tumor models of human cancer continue to evolve, and they represent an important screening tool. However, there is a tremendous need to improve the physiological relevance and reliability of these in vitro models to fulfill today's research requirements for better understanding of cancer progression and treatment options at different stages of the disease. This review describes the hepatocellular carcinoma microenvironmental characteristics and illustrates the current immunotherapy strategy to fight the disease. Moreover, we present a recent collection of 2D and 3D in vitro liver cancer models and address the next generation of in vitro systems recapitulating the tumor microenvironment complexity in more detail.

6.
Cancers (Basel) ; 13(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34680324

RESUMO

Anti-PD-1/L1 immunotherapy has been intensively used in heavily treated population with advanced gastric adenocarcinoma. However, the immunotherapeutic efficacy is low even in PD-L1 positive patients. We aimed to establish a new strategy based on the co-expression of CMTM6/4 and PD-L1 for patient stratification before immunotherapy. By analyzing the data obtained from TCGA and single-cell RNA sequencing at the mRNA level, and 6-color multiplex immunofluorescence staining of tumor tissues in tissue array and 48-case pre-immunotherapy patients at the protein level, we found that CMTM6/4 and PD-L1 co-expressed in both epithelial and mesenchymal regions of gastric adenocarcinoma. The tumor tissues had higher levels of CMTM6/4 expression than their adjacent ones. A positive correlation was found between the expression of CMTM6/4 and the expression of PD-L1 in tumor epithelium. Epithelial co-expression of CMTM6/4 and PD-L1 in gastric tumor region was associated with shorter overall survival but better short-term response to anti-PD-1/L1 immunotherapy. Thus, we developed a predictive model and three pathological patterns based on the membrane co-expression of CMTM6/4 and PD-L1 in tumor epithelial cells for pre-immunotherapy patient screening in gastric adenocarcinoma.

7.
Front Immunol ; 12: 719727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621268

RESUMO

Infectious pneumonia is one of the most common complications after bone marrow transplantation (BMT), which is considered to be associated with poor reconstitution and functional maturation of alveolar macrophages (AMs) post-transplantation. Here, we present evidence showing that lack of IL-13-secreting group 2 innate lymphoid cells (ILC2s) in the lungs may underlay poor AM reconstitution in a mouse model of haploidentical BMT (haplo-BMT). Recombinant murine IL-13 was able to potentiate monocyte-derived AM differentiation in vitro. When intranasally administered, a cocktail of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and CCL2 not only promoted donor monocyte-derived AM reconstitution in haplo-BMT-recipient mice but also enhanced the innate immunity of the recipient animals against pulmonary bacterial infection. These results provide a useful clue for a clinical strategy to prevent pulmonary bacterial infection at the early stage of recipients post-BMT.

8.
J Gastrointest Oncol ; 12(4): 1851-1859, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532133

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains dismal. Hence, it is important to identify the diagnostic and prognostic biomarkers for HCC. Urokinase plasminogen activator (uPA), an extracellular matrix (ECM)-degrading protease, plays a pivotal role in the invasion and metastasis of HCC. Methods: To confirm the clinical significance of uPA in HCC, we explored uPA expression in HCC in The Cancer Genome Atlas (TCGA) database. The expression level of uPA was further verified by quantitative reverse transcription polymerized chain reaction (qRT-PCR) in 133 pairs of primary HCC samples. A survival analysis was conducted with the Kaplan-Meier method in the HCC samples and TCGA database. Results: Our results showed that uPA was overexpressed in HCC and was significantly associated with HCC tumor size (P=0.015), differentiation grade (P=0.028), and absence of tumor encapsulation (P=0.010). Patients with high uPA expression levels had a poor outcome (P=0.026). TCGA database analysis was also consistent with our experimental results. Conclusions: In conclusion, our findings revealed that uPA was overexpressed in HCC and was related to HCC malignant features including tumor size, differentiation grade and absence of tumor encapsulation. High uPA expression had a shorter survival time. It is a potential prognostic biomarker of HCC.

9.
Adv Mater ; : e2105039, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561901

RESUMO

The oxidation of transition metal dichalcogenides (TMDCs) has been extensively studied and applied in electronics, optics, and energy sources because of its tunable structure and performance. However, due to the lack of appropriate technology, dynamically observe the oxidation process remains an arduous task. Herein, the synergistic oxidation between edge and basal plane in molybdenum disulfide (MoS2 ) is observed through electrogenerated chemiluminescence (ECL) blinking with a millisecond resolution. In addition, the ECL method provides a simple, convenient, and quick way to judge structural changes. The transient elevation of the ECL intensity proved the intermittent doping of oxygen at MoS2 , which generates O-atom active sites. High ECL intensity enhanced from the produced hydroperoxide intermediates eases the monitoring of MoS2 particles. Further study shows that the formation of sulfur vacancies at MoS2 , by the edge activation of hydrogen peroxide and the migration of oxygen to the basal plane, is more conducive to oxygen doping that favors the formation of MoOMo as new active sites to induce bursts. The revealing of sulfur vacancy-governed blinking from MoS2 indicates a complex interaction between oxygen and MoS2 . The same phenomenon is observed on tungsten disulfide (WS2 ), which provides new information about the oxidation feature of 2D dichalcogenides.

10.
J Craniofac Surg ; 32(6): 2024-2028, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34516069

RESUMO

ABSTRACT: Fat repositioning is an effective way to treat tear trough deformity (TTD) in Asians. Recent techniques mainly focused on the fixation technique, whereas how to precisely shape and individually quantify the fat pedicle has been ignored. This article introduced an individualized, targeted, and tension-free technique to fabricate a fan-shaped thin septum fat pedicle for repositioning. Furthermore, a layer-level fixation method was advocated to provide sufficient, continuous, uninterrupted filling of the TTD. From January 1, 2009, to December 31, 2018, 492 patients underwent this procedure. Through a transconjunctival incision, a continuous fan-shaped, tension-free, customized septum fat pedicle was precisely designed to match the TTD anatomy. The pedicle could either be elongated, or thickened, or debulked, or translocated, to meet the patients' individual needs. At the same time, a layer-level fat pedicle fixation technique was applied to fully interrupt the TTD. The mean operation time was 60 ±â€Š9.3 minutes. All patients demonstrated a significant improvement with elimination of both eye bags and TTD. High satisfaction was noted among the patients. No obvious resorption of the fat pedicles was observed, and the lower lid contour improvements were durable. One infection occurred after 3 days of surgery, and was resolved by removal of the suture followed by topical application of iodine and oral antibiotics for 3 to 5 days. No other complications were observed. Precisely repositioning transconjunctival fat using a layer-level fixation technique with a fan-shaped thin fat pedicle under a subperiosteal plane is an effective, lasting, and safe approach for individually treating TTD.


Assuntos
Blefaroplastia , Tecido Adiposo/transplante , Pálpebras/cirurgia , Humanos , Suturas
11.
Biomed Environ Sci ; 34(8): 650-655, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34474727

RESUMO

Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens. In comparison with those of the commercial quantitative polymerase chain reaction (qPCR), the sensitivity of the EBV and CMV ICR-RAAs using extracted DNA was 93.33% and 84.84%, respectively; the specificity was 98.75% and 100.00%, respectively; and the Kappa values were 0.930 and 0.892 ( P < 0.05), respectively. In comparison with those of qPCR, the sensitivity of the EBV and CMV ICR-RAAs using the DNA by thermal lysis was 72.22% and 80.00%, respectively; the specificity was 100.00%; and the Kappa values were 0.764 and 0.878 ( P < 0. 05), respectively. Thus, rapid and specific detection of EBV and CMV is possible using ICR-RAA assays.


Assuntos
Citomegalovirus/genética , DNA Viral/análise , Herpesvirus Humano 4/genética , Técnicas de Amplificação de Ácido Nucleico , Recombinases/genética , Adolescente , Adulto , Criança , Pré-Escolar , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 877-881, 2021.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34535200

RESUMO

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Asma/tratamento farmacológico , Criança , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Estudos Prospectivos , Qualidade de Vida
14.
Methods Mol Biol ; 2388: 27-34, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524659

RESUMO

Natural killer T (NKT) cells have been shown to bridge innate and adaptive immunity. However, the rare population and hard-to-transfect of primary NKT cells slow down our understanding of cellular and molecular mechanisms of NKT development and function. To overcome these drawbacks, NKT hybridomas, especially DN32.D3 cells, are applied to study NKT cells in vitro and becoming a valuable tool. Here, we describe the method in the genetic manipulation of DN32.D3 cells by retrovirus, including the generation and concentration of retrovirus, retroviral transduction of DN32.D3 cells, and evaluation of transduction efficiency.

15.
Virol Sin ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398429

RESUMO

Human respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015-2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A (RSV-A) was the predominant subgroup during this research period except in 2016. Totally, 535 sequences of the second hypervariable region (HVR-2) of the G gene were obtained. Combined with 182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1 (512), NA1 (6) and GA5 (3), respectively; while 196 RSV-B sequences fell in BA9 (193) and SAB4 (3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258Q and H266L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than 10%, while the sequences with T290I and T312I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites (296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015-2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

16.
Cancer Res ; 81(20): 5296-5310, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34400394

RESUMO

The most recent American Dietary Guidelines (2020-2025) recommend shifting dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in oils regulate immune cell function and cancer risk remains unclear. Here we demonstrated that high-fat diets (HFD) rich either in OA or LA induced a similar degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor growth. LA impaired antitumor T-cell responses by promoting naïve T-cell apoptosis and inhibiting TNFα production. While exogenous OA and LA were taken up by T cells with similar efficacy, only LA induced significant mitochondrial reactive oxygen species production and lipid peroxidation. Importantly, naïve T cells predominantly expressed epidermal fatty acid binding protein (E-FABP), which is central in facilitating LA mitochondrial transport and cardiolipin incorporation. Genetic depletion of E-FABP rescued LA-impaired T-cell responses and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these data suggest that dietary oils high in LA promote mammary tumors by inducing E-FABP-mediated T-cell dysfunction. SIGNIFICANCE: These findings suggest that modulation of dietary oil composition and inhibition of E-FABP activity may represent novel strategies to enhance T-cell function in the prevention and treatment of obesity-associated cancers.

17.
Respiration ; 100(11): 1097-1104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34412056

RESUMO

BACKGROUND: The treatment of pulmonary malignancies remains a challenge. The efficacy and safety of bronchoscopic radiofrequency ablation (RFA) for the treatment of lung cancer are not well elucidated. OBJECTIVE: This study aimed to evaluate the feasibility and safety of RFA guided by bronchoscopic transparenchymal nodule access (BTPNA) in vivo. METHODS: In an attempt to determine the parameters of RFA, we first performed RFA in conjunction with automatic saline microperfusion in the lung in vitro with various ablation energy (10, 15, 20, 25, and 30 W) and ablation times (3, 5, 8, and 10 min). The correlation between ablated area and RFA parameter was recorded and analyzed. Further, we conducted a canine study with RFA by BTPNA in vivo, observing the ablation effect and morphological changes in the lung assessed by chest CT and histopathologic examination at various follow-up time points (1 day, n = 3; 30 days, n = 4; 90 days, n = 4). The related complications were also observed and recorded. RESULTS: More ablation energy, but not ablation time, induced a greater range of ablation area in the lung. Ablation energy applied with 15 W for 3 min served as the appropriate setting for pulmonary lesions ≤1 cm. RFA guided by BTPNA was performed in 11 canines with 100% success rate. Inflammation, congestion, and coagulation necrosis were observed after ablation, which could be repaired within 7 days; subsequently, granulation and fibrotic scar tissue developed after 30 days. No procedure-related complication occurred during the operation or in the follow-up periods. CONCLUSION: The novel RFA system and catheter in conjunction with automatic saline microperfusion present a safe and feasible modality in pulmonary parenchyma. RFA guided by BTPNA appears to be well established with an acceptable tolerance; it might further provide therapeutic benefit in pulmonary malignancies.

18.
Epigenomics ; 13(15): 1231-1245, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34318684

RESUMO

During the last two decades, diverse epigenetic modifications including DNA methylation, histone modifications, RNA editing and miRNA dysregulation have been associated with psychiatric disorders. A few years ago, in a review we outlined the most common epigenetic alterations in major psychiatric disorders (e.g., aberrant DNA methylation of DTNBP1, HTR2A, RELN, MB-COMT and PPP3CC, and increased expression of miR-34a and miR-181b). Recent follow-up studies have uncovered other DNA methylation aberrations affecting several genes in mental disorders, in addition to dysregulation of many miRNAs. Here, we provide an update on new epigenetic findings and highlight potential origin of the diversity and inconsistencies, focusing on drug effects, tissue/cell specificity of epigenetic landscape and discuss shortcomings of the current diagnostic criteria in mental disorders.

19.
J Hepatocell Carcinoma ; 8: 759-771, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268259

RESUMO

Purpose: By using integrative RNA sequencing analysis, we identified a novel tumor suppressor, serpin family A member 11 (SERPINA11), which is a serine proteinase inhibitor that belongs to the serpin superfamily. However, the function of SERPINA11 in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role and molecular mechanism of SERPINA11 in HCC. Methods: Gene expression patterns of SERPINA11 were analyzed in tissue samples of HCC patients by qRT-PCR. In vitro and in vivo experiments were performed to characterize the function and molecular mechanism of SERPINA11 in the tumor metastasis capacity. Results: SERPINA11 was downregulated in approximately 50% of HCC and significantly associated with metastasis and poor outcome of patients. Functional study demonstrated that SERPINA11 could inhibit cell growth, cell migration and tumor metastasis. Mechanistic investigations suggested that SERPINA11 accelerated urokinase-type plasminogen activator (uPA) degradation to suppress extracellular signal-regulated kinase (ERK1/2) phosphorylation, and thereby subdued metastatic capabilities of HCC cells. Conclusion: SERPINA11 plays an important tumor suppressive role in HCC, with possible use as a biomarker and an intervention point for new therapeutic strategies.

20.
Food Chem ; 365: 130470, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34237577

RESUMO

To explore the antioxidant capacity of citrus flavonoids under different evaluation systems, chemical and biological methods were engaged to determine the antioxidant abilities of flavanones and polymethoxyflavones. Results showed that flavanones exhibited good antioxidant activity, while polymethoxyflavones had a weak ability to scavenge free radicals. Both flavanones and polymethoxyflavones exerted the ability to inhibit H2O2-induced oxidative stress, but the effective concentration of polymethoxyflavones was lower. Further exploration showed that neohesperidin and tangeretin selectively regulated antioxidant enzyme activity, both in vitro and in vivo. Tangeretin also maintained the expression of antioxidant enzymes in L02 cells and in ICR mice liver. The mechanism exploration showed that both neohesperidin and tangeretin promoted the expression of NRF2 and inhibit the expression of KEAP1, but tangeretin could inhibit the ubiquitination of NRF2 by inhibiting CUL3. The mechanism was verified by CUL3 gene silencing. This study demonstrates a novel antioxidant mechanism of natural products.


Assuntos
Antioxidantes , Fator 2 Relacionado a NF-E2 , Animais , Proteínas Culina/metabolismo , Flavonas , Peróxido de Hidrogênio , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ubiquitinação
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