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1.
Biomaterials ; 302: 122332, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37801790

RESUMO

The treatment efficacies of conventional medications against colorectal cancer (CRC) are restricted by a low penetrative, hypoxic, and immunosuppressive tumor microenvironment. To address these restrictions, we developed an innovative antitumor platform that employs calcium overload-phototherapy using mitochondrial N770-conjugated mesoporous silica nanoparticles loaded with CaO2 (CaO2-N770@MSNs). A loading level of 14.0 wt% for CaO2-N770@MSNs was measured, constituting an adequate therapeutic dosage. With the combination of oxygen generated from CaO2 and hyperthermia under near-infrared irradiation, CaO2-N770@MSNs penetrated through the dense mucus, accumulated in the colorectal tumor tissues, and inhibited tumor cell growth through endoplasmic reticulum stress and mitochondrial damage. The combination of calcium overload and phototherapy revealed high therapeutic efficacy against orthotopic colorectal tumors, alleviated the immunosuppressive microenvironment, elevated the abundance of beneficial microorganisms (e.g., Lactobacillaceae and Lachnospiraceae), and decreased harmful microorganisms (e.g., Bacteroidaceae and Muribaculaceae). Moreover, together with immune checkpoint blocker (αPD-L1), these nanoparticles showed an ability to eradicate both orthotopic and distant tumors, while potentiating systemic antitumor immunity. This treatment platform (CaO2-N770@MSNs plus αPD-L1) open a new horizon of synergistic treatment against hypoxic CRC with high killing power and safety.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Nanopartículas , Humanos , Cálcio , Linhagem Celular Tumoral , Fototerapia , Neoplasias Colorretais/terapia , Imunoterapia , Hipóxia , Microambiente Tumoral
2.
Front Oncol ; 13: 1206196, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564931

RESUMO

Background: Postoperative ileus (POI) is a common complication following abdominal surgery, which can lead to significant negative impacts on patients' well-being and healthcare costs. However, the efficacy of current treatments is not satisfactory. The purpose of this study was to evaluate the therapeutic effects of acupuncture intervention and explore the regulation of acupoint selection for treating POI in colorectal cancer (CRC) patients. Methods: We searched eight electronic databases to identify randomized controlled trials (RCTs) on acupuncture for POI in CRC and conducted a meta-analysis. Subsequently, we utilized the Apriori algorithm and the Frequent pattern growth algorithm, in conjunction with complex network and cluster analysis, to identify association rules of acupoints. Results: The meta-analysis showed that acupuncture led to significant reductions in time to first defecation (MD=-20.93, 95%CI: -25.35, -16.51; I2 = 93.0%; p < 0.01; n=2805), first flatus (MD=-15.08, 95%CI: -18.39, -11.76; I2 = 96%; p < 0.01; n=3284), and bowel sounds recovery (MD=-10.96, 95%CI: -14.20, -7.72; I2 = 94%; p < 0.01; n=2043). A subgroup analysis revealed that acupuncture not only reduced the duration of POI when administered alongside conventional care but also further expedited the recovery of gut function after colorectal surgery when integrated into the enhanced recovery after surgery (ERAS) pathway. The studies included in the analysis reported no instances of serious adverse events associated with acupuncture. We identified Zusanli (ST36), Shangjuxu (ST37), Neiguan (PC6), Sanyinjiao (SP6), Xiajuxu (ST39), Hegu (LI4), Tianshu (ST25), and Zhongwan (RN12) as primary acupoints for treating POI. Association rule mining suggested potential acupoint combinations including {ST37, ST39}≥{ST36}, {PC6, ST37}≥{ST36}, {SP6, ST37}≥{ST36}, and {ST25, ST37}≥{ST36}. Conclusion: Meta-analysis indicates acupuncture's safety and superior effectiveness over postoperative care alone in facilitating gastrointestinal recovery. Machine-learning approaches highlight the importance of the lower He-sea points, including Zusanli (ST36) and Shangjuxu (ST37), in treating POI in CRC patients. Incorporating additional acupoints such as Neiguan (PC6) (for pain and vomiting) and Sanyinjiao (SP6) (for abdominal distension and poor appetite) can optimize treatment outcomes. These findings offer valuable insights for refining treatment protocols in both clinical and experimental settings, ultimately enhancing patient care.

3.
Biomed Pharmacother ; 165: 115223, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37523984

RESUMO

Dendrobium, which belongs to the family of Orchidaceae, is a highly valuable traditional Chinese medicine commonly used in China. It exerts pharmacological activities such as antitumor and hypoglycemia effects, and its main components are alkaloids, polysaccharides, and terpenoids, among others. In recent years, research on the clinical application of Dendrobium in antitumor therapy has gained increasing attention. Accumulating evidence suggests that the active components of Dendrobium possess significant inhibitory effects on the viability of cancer cells as evident from in vivo and in vitro experiments, which indicates that Dendrobium exerts significant anticancer effect in treating and preventing cancer development, inhibiting the underlying potential molecular mechanisms, including suppression of cancer cell growth and proliferation, epithelial-mesenchymal transition (EMT), apoptosis induction, tumor angiogenesis, and reinforcement of cisplatin (DDP) -induced apoptosis. We herein present a review that summarizes the research progress of the application of Dendrobium in cancer therapy and its molecular mechanisms. This review describes the positive aspects of the active ingredients of Dendrobium in the treatment of cancers in various systems of the human body, their inhibitory effects on tumor survival and tumor microenvironment, and their potential mechanisms. Additionally, this review proposes future application prospects of Dendrobium in cancer therapy to promote further research and future extensive clinical applications of Dendrobium in cancer therapy.


Assuntos
Alcaloides , Dendrobium , Humanos , Corpo Humano , Extratos Vegetais/farmacologia , Alcaloides/farmacologia , Apoptose
4.
PeerJ ; 11: e14984, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187528

RESUMO

Objective: As the primary means of plant-induced haploid, anther culture is of great significance in quickly obtaining pure lines and significantly shortening the potato breeding cycle. Nevertheless, the methods of anther culture of tetraploid potato were still not well established. Methods: In this study, 16 potato cultivars (lines) were used for anther culture in vitro. The corresponding relation between the different development stages of microspores and the external morphology of buds was investigated. A highly-efficient anther culture system of tetraploid potatoes was established. Results: It was shown in the results that the combined use of 0.5 mg/L 1-Naphthylacetic acid (NAA), 1.0 mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D), and 1.0 mg/L Kinetin (KT) was the ideal choice of hormone pairing for anther callus. Ten of the 16 potato cultivars examined could be induced callus with their respective anthers, and the induction rate ranged from 4.44% to 22.67% using this hormone combination. According to the outcome from the orthogonal design experiments of four kinds of appendages, we found that the medium with sucrose (40 g/L), AgNO3 (30 mg/L), activated carbon (3 g/L), potato extract (200 g/L) had a promotive induction effect on the anther callus. In contrast, adding 1 mg/L Zeatin (ZT) effectively facilitated callus differentiation. Conclusion: Finally, 201 anther culture plantlets were differentiated from 10 potato cultivars. Among these, Qingshu 168 and Ningshu 15 had higher efficiency than anther culture. After identification by flow cytometry and fluorescence in situ hybridization, 10 haploid plantlets (5%), 177 tetraploids (88%), and 14 octoploids (7%) were obtained. Some premium anther-cultured plantlets were further selected by morphological and agronomic comparison. Our findings provide important guidance for potato ploidy breeding.


Assuntos
Solanum tuberosum , Solanum tuberosum/genética , Tetraploidia , Hibridização in Situ Fluorescente , Melhoramento Vegetal , Hormônios
5.
Zhongguo Zhong Yao Za Zhi ; 48(4): 1087-1097, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872279

RESUMO

The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.


Assuntos
Farmacologia em Rede , Osteoporose , Humanos , Simulação de Acoplamento Molecular , Osteogênese , Fosfatidilinositol 3-Quinases , Bases de Dados Genéticas
6.
Food Chem ; 412: 135542, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36706505

RESUMO

Chinese cabbage is a nutrients-rich vegetable with diverse leaf colors. Here, we used widely-targeted metabolomics technology to study the metabolic responses of three Chinese cabbage varieties with representative leaf colors after blue light treatment. The inner leaf color of orange varieties 20S530 and 15S1094 changed from yellow to golden yellow, while no visible color change occurred in the common variety 14S23 after the treatment. A total of 844 metabolites were measured from the leaf samples of these three varieties in a time course study after short term blue light treatment, with kaempferol-4'-O-glucoside, isoquercitrin, hyperin, arbutin, sulforaphane as enriched nutritional metabolites. Orange Chinese cabbage varieties showed additional nutrition enhancement after the treatment. This study is the first to explore the global metabolic responses of Chinese cabbage after blue light treatment, and our findings provided valuable insights on how to effectively use lighting conditions to enhance specific groups of nutrients in vegetables.


Assuntos
Brassica , Brassica/metabolismo , Luz , Verduras , Metabolômica , Valor Nutritivo
7.
Crit Rev Food Sci Nutr ; 63(24): 7091-7107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35199615

RESUMO

Prunus mume Sieb. Et Zucc (P. mume) is an acidic fruit native to China (named Chinese Mei or greengage plum). It is currently cultivated in several Asian countries, including Japan ("Ume"), Korea (Maesil), and Vietnam (Mai or Mo). Due to its myriad nutritional and functional properties, it is accepted in different countries, and its characteristics account for its commercialization. In this review, we summarize the information on the bioactive compounds from the fruit of P. mume and their structure-activity relationships (SAR); the pulp has the highest enrichment of bioactive chemicals. The nutritional properties of P. mume and the numerous uses of its by-products make it a potential functional food. P. mume extracts exhibit antioxidant, anticancer, antimicrobial, and anti-hyperuricaemic properties, cardiovascular protective effects, and hormone regulatory properties in various in vitro and in vivo assays. SAR shows that the water solubility, molecular weight, and chemical conformation of P. mume extracts are closely related to their biological activity. However, further studies are needed to evaluate the fruit's potential nutritional and functional therapeutic mechanisms. The industrial process of large-scale production of P. mume and its extracts as functional foods or nutraceuticals needs to be further optimized.


Assuntos
Prunus , Prunus/química , Frutas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Relação Estrutura-Atividade , Suplementos Nutricionais
8.
Oxid Med Cell Longev ; 2022: 6986445, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466092

RESUMO

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Ferroptosis is emerging as an effective target for tumor treatment as it has been shown to potentiate cell death in some malignancies. However, it remains unclear whether histone phosphorylation events, an epigenetic mechanism that regulates transcriptional expression, are involved in ferroptosis. Our study found that supplementation with anisomycin, an agonist of p38 mitogen-activated protein kinase (MAPK), induced ferroptosis in HCC cells, and the phosphorylation of histone H3 on serine 10 (p-H3S10) was participated in anisomycin-induced ferroptosis. To investigate the anticancer effects of anisomycin-activated p38 MAPK in HCC, we analyzed cell viability, colony formation, cell death, and cell migration in Hep3B and HCCLM3 cells. The results showed that anisomycin could significantly suppress HCC cell colony formation and migration and induce HCC cell death. The hallmarks of ferroptosis, such as abnormal accumulation of iron and elevated levels of lipid peroxidation and malondialdehyde, were detected to confirm the ability of anisomycin to promote ferroptosis. Furthermore, coincubation with SB203580, an inhibitor of activated p38 MAPK, partially rescued anisomycin-induced ferroptosis. And the levels of p-p38 MAPK and p-H3S10 were successively increased by anisomycin treatment. The relationship between p-H3S10 and ferroptosis was revealed by ChIP sequencing. The reverse transcription PCR and immunofluorescence results showed that NCOA4 was upregulated both in mRNA and protein levels after anisomycin treatment. And by C11-BODIPY staining, we found that anisomycin-induced lipid reactive oxygen species was reduced after NCOA4 knockdown. In conclusion, the anisomycin-activated p38 MAPK promoted ferroptosis of HCC cells through H3S10 phosphorylation.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Fosforilação , Anisomicina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Serina , Histonas , Fatores de Transcrição
9.
Bioorg Med Chem ; 69: 116916, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35792403

RESUMO

Microglia-induced neuroinflammation plays a critical role in neurological diseases. At present, RIPK2 is considered to participate in inflammatory and autoimmune cellular pathways and diseases. RIPK2 is found to be a pivotal therapeutic target in neurologic disorders related to inflammation. In our research, we discovered the protective function of tunicatachalcone (TC) against neuroinflammation. TC is a natural chalcone compound derived from Pongamia pinnata, a medicinal plant. The results revealed that TC (5-20 µM) ameliorated the activation of BV-2 microglia induced by lipopolysaccharide (LPS) in a dose-dependent way, which was proved by the reduced production of inflammation-related mediators. By using SPR-LC-MS/MS analysis, we revealed the potent inhibitory function of TC against neuroinflammation mediated by microglia via targeting RIPK2. A strong binding between TC and RIPK2 was further demonstrated based on the results of SPR, MST and molecular modeling. Through applying mRNA transcriptomics and bioinformatics analysis, it was demonstrated that TC could mediate RIPK2-dependent gene transcription to exert the neuroprotective effect. In summary, our research presented that RIPK2 was a possible therapeutic target of TC.


Assuntos
Produtos Biológicos , Microglia , Produtos Biológicos/farmacologia , Cromatografia Líquida , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Doenças Neuroinflamatórias , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/farmacologia , Espectrometria de Massas em Tandem
10.
J Environ Manage ; 317: 115348, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35660832

RESUMO

To ensure the efficiency of anaerobic biological treatment technology at lower temperature will expand the application of anaerobic reactor in practical industrial wastewater treatment. Through a batch experiment, asparagine, corncob biochar and Fe2+ were selected as strengthening measures to analyze the effects on the anaerobic sludge characteristics, microbial community and functional genes in the low temperature (15 °C). Results showed that after 21 days, asparagine began to promote chemical oxygen demand (COD) removal by the anaerobic treatment, with highest COD removal rate (81.65%) observed when the asparagine concentration was 1 mmol/L. When adding 3 g biochar, 25 mg/L Fe2+, and the combination of biochar and Fe2+, the COD removal rates reached to 82%, 92% and 97%, respectively. In the presence of asparagine, both biochar and Fe2+ alone or in combination increased the activity of protease (16.35%-120.71%) and coenzyme F420 (5.63%-130.2%). The relative abundance of Proteobacteria and Methanobacterium increased in the presence of biochar and Fe2+. In addition, the KEGG results showed that the combined addition of biochar and Fe2+ enhanced bacterial replication and repair and promoted amino acid metabolism of archaea.


Assuntos
Asparagina , Microbiota , Anaerobiose , Reatores Biológicos/microbiologia , Carvão Vegetal/química , Compostos Ferrosos , Esgotos/química , Temperatura , Zea mays
11.
Nat Commun ; 11(1): 4457, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901017

RESUMO

Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.


Assuntos
Ácidos Graxos Voláteis/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Interleucinas/biossíntese , Animais , Butiratos/imunologia , Butiratos/metabolismo , Butiratos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Citrobacter rodentium , Colite/imunologia , Colite/microbiologia , Colite/prevenção & controle , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/prevenção & controle , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Microbioma Gastrointestinal/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas In Vitro , Interleucinas/deficiência , Interleucinas/genética , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Regiões Promotoras Genéticas , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Interleucina 22
12.
Phytochemistry ; 178: 112460, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32692662

RESUMO

Paris polyphylla var. yunnanensis can synthesize Paris saponins with multiple effective therapies, and its rhizome has become an indispensable ingredient in many patented drugs. However, how Paris saponin content changes in tissues at different stages and the molecular mechanisms underlying the production and accumulation of the bioactive compounds are unclear. This study aimed to uncover the mechanisms underlying the biosynthesis and accumulation by integrating transcriptome sequencing and phytochemical investigation of the leaves and rhizomes at different growth stages. Paris saponin content in leaves was lower during the fruiting stage than the vegetative stage, whereas the content in rhizomes increased during the fruiting stage. The candidate genes related to Paris saponin biosynthesis were determined by transcriptome analyses. Most biosynthetic genes were found to be abundantly expressed in the leaves during the vegetative stage in the light of expression profiles and functional enrichment results. The expression patterns of the differentially expressed genes related to the biosynthesis were positively correlated with the accumulation of saponins in tissues. These findings suggest that both leaves and rhizomes are capable of biosynthesizing Paris saponins, and that aerial plant parts can be used to extract them. The different patterns of biosynthesis and accumulation in the leaves and rhizomes were also determined here. This study will help improve our understanding of the mechanisms underlying the biosynthesis and accumulation of Paris saponins, and aid in the comprehensive development and utilization of this medicinal plant.


Assuntos
Liliaceae , Saponinas , Perfilação da Expressão Gênica , Folhas de Planta , Rizoma
13.
Food Chem Toxicol ; 136: 110955, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31712109

RESUMO

Dibutyl phthalate (DBP) is a ubiquitous environmental contaminant that at certain levels can be harmful to human health. Although DBP has been widely linked to immunotoxicity, any association between DBP exposure and splenic injury remains unknown. The purpose of this study was to investigate whether DBP exposure can induce splenic injury and the antagonistic effects of two antioxidants, vitamin E (VitE) and curcumin (Cur), on DBP-induced splenic injury. The levels of ROS, GSH, T-AOC, IL-1ß, TNF-α, cytochrome C, caspase-8, caspase-9 and caspase-3 in the spleen homogenate of mice were measured. Any histopathological changes in the spleen were observed using H&E and toluidine blue staining. And the morphology of mitochondria was observed using Janus Green B staining. The results indicate that exposure to 50 mg/kg DBP could cause histopathological changes of the spleen and result in inflammation and apoptosis associated with oxidative stress, which may lead to splenic injury in mice. Moreover, both VitE and Cur could antagonize the oxidative stress induced by DBP to reduce splenic injury. These findings help to expand our understanding of DBP-mediated immunotoxicity, and to show that VitE and Cur can alleviate DBP-induced splenic injury and the possible DBP-associated decline in immune function.


Assuntos
Curcumina/uso terapêutico , Dibutilftalato/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Esplenopatias/induzido quimicamente , Esplenopatias/prevenção & controle , Vitamina E/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Mitocôndrias/patologia , Baço/efeitos dos fármacos , Baço/patologia , Esplenopatias/patologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Cancer Med ; 9(1): 179-193, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31724326

RESUMO

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/epidemiologia , Transcriptoma/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Regulação para Baixo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular/métodos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Medicina de Precisão/métodos , Prognóstico , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , RNA-Seq , Curva ROC , Medição de Risco/métodos , Transcriptoma/efeitos dos fármacos , Regulação para Cima
15.
J Immunol ; 203(1): 282-292, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31076530

RESUMO

The gut microbiota has been shown critical for mucosal adjuvant activity of cholera toxin (CT), a potent mucosal adjuvant. However, the mechanisms involved remain largely unknown. In this study, we report that depletion of gut bacteria significantly decreased mucosal and systemic Ab responses in mice orally immunized with OVA and CT. Feeding mice short-chain fatty acids (SCFAs) promoted Ab responses elicited by CT, and, more importantly, rescued Ab responses in antibiotic-treated mice. In addition, mice deficient in GPR43, a receptor for SCFAs, showed impaired adjuvant activity of CT. Administering CT did not promote SCFA production in the intestines; thus, SCFAs facilitated but did not directly mediate the adjuvant activity of CT. SCFAs promoted B cell Ab production by promoting dendritic cell production of BAFF and ALDH1a2, which induced B cell expression of IFN regulatory factor 4, Blimp1, and XBP1, the plasma B cell differentiation-related genes. Furthermore, when infected with Citrobacter rodentium, GPR43-/- mice exhibited decreased Ab responses and were more susceptible to infection, whereas the administration of SCFAs promoted intestinal Ab responses in wild-type mice. Our study thereby demonstrated a critical role of gut microbiota and their metabolite SCFAs in promoting mucosal adjuvant activity of CT through GPR43.


Assuntos
Adjuvantes Imunológicos/metabolismo , Linfócitos B/imunologia , Toxina da Cólera/metabolismo , Citrobacter rodentium/fisiologia , Células Dendríticas/imunologia , Infecções por Enterobacteriaceae/imunologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Família Aldeído Desidrogenase 1/metabolismo , Animais , Formação de Anticorpos , Fator Ativador de Células B/metabolismo , Diferenciação Celular , Imunidade nas Mucosas , Camundongos , Camundongos Knockout , Comunicação Parácrina , Receptores Acoplados a Proteínas G/genética , Retinal Desidrogenase/metabolismo
16.
Biomed Res Int ; 2019: 5280514, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032350

RESUMO

The study aims to investigate the effects of the alcohol extract of Coreopsis tinctoria Nutt (AC) on diabetic nephropathy (DN) mice. A total of 30 db/db (DN) mice were divided into 3 groups, which were treated with AC (300 mg/kg/day), metformin (180 mg/kg/day), or saline by gavage for 10 weeks. Ten db/m mice treated with saline were used as normal control (NC group). Body weight (BW) and fasting blood glucose (FBG), HbA1c, 24 h urinary albumin excretion (UAE), and renal pathological fibrosis were analyzed. Expression of miR-192, miR-200b, and proteins in the PTEN/PI3K/AKT pathway was analyzed by qPCR or western blot. The DN mice had significantly higher BW, FBG, and 24 h UAE, as well as more severe pathological fibrosis when compared with NC. Treatment of AC could decrease BW, FBG, and 24 h UAE and alleviated kidney damage. Compared with the NC group, expressions of miR-192 and miR-200b were increased, whereas their target proteins (ZEB2 and PTEN) were reduced in the kidneys of DN mice, which further modulated the expression of their downstream proteins PI3K p85α, P-AKT, P-smad3, and COL4 α1; these proteins were increased in the kidneys of DN mice. In contrast, AC treatment reversed the expression changes of these proteins. These findings demonstrate that AC may protect the kidneys of DN mice by decreasing miR-192 and miR-200b, which could further regulate their target gene expression and modulate the activity of the PTEN/PI3K/AKT pathway to reduce the degree of renal fibrosis.


Assuntos
Coreopsis/química , Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , MicroRNAs/genética , Albuminúria/urina , Álcoois/química , Animais , Glicemia/isolamento & purificação , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Diabetes Mellitus/urina , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/urina , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hemoglobinas Glicadas/isolamento & purificação , Humanos , Rim/efeitos dos fármacos , Rim/fisiologia , Camundongos , Camundongos Endogâmicos NOD , PTEN Fosfo-Hidrolase/genética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
17.
Bioelectrochemistry ; 128: 49-55, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30917334

RESUMO

An effective and biodegradable Ficus tikoua leaves extract was studied as a corrosion inhibitor for carbon steel in hydrochloric acid. Systematic electrochemical experiments and morphological characterization were carried out to investigate the properties of the corrosion inhibitor. Meanwhile, quantum chemical calculations were performed to aid further understanding of the electrochemical mechanism. The electrochemical results reveal that the extract inhibitors act as a mixed-type with an inhibition efficiency up to 95.8% at 298 K. Moreover, this extract shows good inhibory activity at a wide range of temperatures and the corresponding results were further confirmed by morphological analysis. The chemical formulae of these major components are fully optimized in the DFT with B3LYP in the gas phase and the base set is 6-311++G (d, p).


Assuntos
Carbono/química , Corrosão , Ficus/química , Ácido Clorídrico/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Aço/química , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
18.
J Ethnopharmacol ; 227: 166-175, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30176347

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Rhizome of Ligusticum chuanxiong Hort. (Abbreviated as LC) is a frequently prescribed component in plenty of traditional Chinese medicine (TCM) formulas which are used to treat diabetic nephropathy (DN). The aims of the present study are to investigate the protective effect of the ethanol extract of LC rhizome (EEL) against DN in vivo, evaluate its potential mechanism, and find the evidence supporting its enthopharmacological use as an anti-DN agent. MATERIALS AND METHODS: Hepa 1c1c7 murine hepatoma cells, human breast carcinoma MDA-MB-231 cells, human renal glomerular endothelial cells (HRGEC), and RAW 264.7 murine macrophages were adopted to test the effects of EEL and its active constituents on inhibitions of oxidative stress and inflammation in vitro. A streptozotocin (STZ) -induced DN C57BL/6 mice model was established and used to investigate the preventive effect of EEL against DN in vivo. RESULTS: EEL demonstrated potential inhibitory effects against oxidative stress and inflammation in vitro. Using a STZ-induced DN mice model, it has been found that EEL treatment significantly prevented STZ-induced increases of urine production, urinary albumin excretion (UAE) and urine albumin-to-creatinine ratio (UACR), and markedly attenuated STZ-induced renal damages (e.g. glomerulosclerosis and fibrosis). The predominant bioactive constituents, Z-ligustilide (LGT), ferulic acid (FA), and tetramethylpyrazine (TMP), were inhibitors of oxidative stress and inflammation through acting with Nrf2 and NF-κB pathways. CONCLUSIONS: EEL attenuates structural and functional damages of kidney in STZ-induced DN model in vivo, which might be related to the functions of EEL on inhibitions of oxidative stress and inflammation. These finding definitely supports the ethnopharmacological use of LC as an anti-DN agent.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Ligusticum , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Rizoma
19.
J Ethnopharmacol ; 221: 37-47, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29660467

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Cinnamomum camphora (L.) J. Presl has been used for the traditional medicine as a therapeutic agent of inflammation-related diseases, including sprains, rheumatic arthritis, abdominal pain, cough and bronchitis, for a long history. The aim of the present study was to illustrate anti-inflammatory substances of C. camphora and their mechanism of action, and to establish the correlations between chemical constituents and traditional uses of this plant. MATERIALS AND METHODS: Chemical constituents were purified by chromatographic methods, and their structures were established based on spectroscopic analysis. Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages was adopted for evaluating the anti-inflammatory activity in vitro. The nitric oxide (NO) production assay and nuclear factor kappa B (NF-κB) dual luciferase reporter assay were used to screen anti-inflammatory constituents. The mRNA and protein levels of inflammation-related cytokines and enzymes were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR), immunoblot analysis, and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: Twenty-five constituents were isolated from the EtOH extract of C. camphora. Eight constituents, covering phenylpropanoid (7), lignans (10 and 22), flavonoids (16-18), coumarin (21), and terpenoid (24) significantly inhibited LPS-stimulated NO production with maximum inhibition rates (MIRs) of ≥ 80%, and thus were verified to be the anti-inflammatory substances of this ethnomedical plant. (+)-Episesaminone (SMO, 22) and 3S-(+)-9-oxonerolidol (NLD, 24) blocked NF-κB activation via inducing IκBα expression. Moreover, SMO and NLD inhibited productions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), and alleviated increased mRNA and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and matrix metallopeptidase-9 (MMP-9) in LPS-stimulated RAW 264.7 macrophages. CONCLUSIONS: The ethnomedical use of C. camphora for the treatment of inflammation-related diseases was attributed to the combined in vitro anti-inflammatory activities of phenylpropanoid, lignan, flavonoid, coumarin, and terpenoid. SMO and NLD were found to be new molecules with in vitro anti-inflammatory activities, which are achieved by inhibiting NF-κB regulated inflammatory response.


Assuntos
Anti-Inflamatórios/farmacologia , Cinnamomum camphora , Macrófagos/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Animais , Anti-Inflamatórios/análise , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Citocinas/genética , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Compostos Fitoquímicos/análise , Componentes Aéreos da Planta , Extratos Vegetais/análise , Células RAW 264.7
20.
Shanghai Kou Qiang Yi Xue ; 15(2): 210-2, 2006 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16685369

RESUMO

PURPOSE: To study the in vitro antimicrobial activity of ethanol extract of salvia miltiorrhiza bunge on several oral pathogenic microbes. METHODS: Antimicrobial activities of ethanol extract of salvia miltiorrhiza bunge for porphyromonas gingivalis ATCC 33277, A. actinomycetes comitans ATCC 24523, Streptococcus mutans, and Lactobacillus were determined using the cup-plate method. The minimum antibacterial concentrations of ethanol extract of salvia miltiorrhiza bunge were measured. SPSS10.0 software package was used for Student's t test. RESULTS: Ethanol extract of salvia miltiorrhiza bunge had antimicrobial activities on Porphyromonas gingivalis, A. actinomycetemcomitans, Streptococcus mutans, Lactobacillus, and the minimum inhibitory concentrations were 15.62 mg/ml, 15.62 mg/ml, 62.50mg/ml and 15.62 mg/ml; The pH of the solution was influential to its antimicrobial activity. CONCLUSION: Ethanol extract of salvia miltiorrhiza bunge has an antimicrobial activity on oral pathogenic microbes.


Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Salvia miltiorrhiza/química , Actinomyces , Etanol , Testes de Sensibilidade Microbiana , Fitoterapia , Raízes de Plantas/química , Porphyromonas gingivalis/efeitos dos fármacos , Salvia/química , Streptococcus mutans/efeitos dos fármacos
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