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1.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2836-2844, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472301

RESUMO

It has been reported that ODB genes play an important role in homologous recombination-directed DNA repair, suggesting their potential applications in plant breeding. To analyze the expression characteristics of tobacco NtODB gene, the cDNA sequence of NtODB was obtained using in silico cloning technique. The physicochemical properties, signal peptide, and advanced structures of the predicted protein were analyzed using bioinformatics tools. The results showed that the NtODB gene has a 579-bp open reading frame which encodes a protein with 192 amino acid residues. The protein NtODB is predicted to be alkaline and hydrophilic. Real-time quantitative PCR showed that NtODB was constitutively expressed in different tissues. Subcellular localization showed that NtODB was mainly expressed in cell membrane and chloroplast. These results may help us to better understand and elucidate the roles of ODB genes in the homologous recombination-directed DNA repair.


Assuntos
Biologia Computacional , Tabaco , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Simulação por Computador , DNA Complementar , Filogenia , Melhoramento Vegetal , Tabaco/genética
2.
Anticancer Drugs ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34561998

RESUMO

The nucleolus is the site of ribosome biogenesis and is found to play an important role in stress sensing. For over 100 years, the increase in the size and number of nucleoli has been considered as a marker of aggressive tumors. Despite this, the contribution of the nucleolus and the biologic processes mediated by it to cancer pathogenesis has been largely overlooked. This state has been changed over the recent decades with the demonstration that the nucleolus controls numerous cellular functions associated with cancer development. Induction of nucleolar stress has recently been regarded as being superior to conventional cytotoxic/cytostatic strategy in that it is more selective to neoplastic cells while sparing normal cells. Natural products represent an excellent source of bioactive molecules and some of them have been found to be able to induce nucleolar stress. The demonstration of these nucleolar stress-inducing natural products has paved the way for a new therapeutic approach to more delicate tumor cell-killing. This review provides a contemporary summary of the role of the nucleolus as a novel promising target for cancer therapy, with particular emphasis on natural products as an exciting new class of anti-cancer drugs with nucleolar stress-inducing properties.

3.
Food Chem ; 363: 130340, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34144416

RESUMO

This study sought to explore the antibacterial mechanism associated with membrane damage in Yersinia enterocolitica by protocatechualdehyde (PCA), thus providing improved knowledge of whether PCA is suitable for pork preservation. The minimum inhibitory concentration (MIC) of PCA was determined by micro-broth dilution. We then characterized functional and morphological changes of Y. enterocolitica treated with PCA. Finally, the growth inhibition model of PCA against Y. enterocolitica in pork was established using the response surface method. Accordingly, the MIC of PCA against Y. enterocolitica was found to be 0.3125 mg/mL. Significant observations incorporated membrane depolarization, a markedly decreased intracellular ATP and pH, and morphological changes induced by PCA treatment. After PCA treatment under low temperatures, the average Y. enterocolitica count in pork decreased by two log cycles. According to the obtained findings, PCA exhibited satisfactory performances as a food preservative to control the growth and reproduction of Y. enterocolitica in pork.


Assuntos
Carne de Porco , Carne Vermelha , Yersinia enterocolitica , Animais , Benzaldeídos , Catecóis , Temperatura Baixa , Microbiologia de Alimentos , Carne , Suínos
4.
J Cancer ; 12(13): 4075-4085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093811

RESUMO

Non-small cell lung cancer (NSCLC) is one of the major cancer-related causes of morbidity and mortality worldwide. Despite the progress in lung cancer treatment, there is still an urgent need to discover novel therapeutic agents for NSCLC. Natural products represent a rich source of bioactive compounds. Through a natural compound library screening assay, we found that a group of anti-insect drugs had significant inhibitory effect on the proliferation of NSCLC cells. Among the anti-insect drugs, two derivatives of artemisinin, i.e., artesunate (ART) and dihydroartemisinin (DHA), a group of well-known anti-malarial drugs, have been shown to possess selective anti-cancer properties. Mechanistically, we found that ART and DHA induced apoptosis of A549 cells as evidenced by decreased protein level of VDAC and increased caspase 3 cleavage. Furthermore, cystine/glutamate transporter (xCT), a core negative regulator of ferroptosis, was downregulated by ART and DHA. The mRNA level of transferrin receptor (TFRC), a positive regulator of ferroptosis, was upregulated by ART and DHA. ART/DHA-induced apoptosis and ferroptosis in NSCLC cells were partly reversed by N-Acetyl-L-cysteine (NAC), a ROS scavenger, and ferrostatin-1, a ferroptosis inhibitor, respectively. These results suggest that artemisinin derivatives have anti-NSCLC activity through induction of ROS-dependent apoptosis/ferroptosis. Our findings provide the experimental basis for the potential application of artemisinin derivatives as a class of novel therapeutic drugs for NSCLC.

5.
Front Oncol ; 11: 656687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150623

RESUMO

Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of breast cancer. Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal-like cells capable of migration, invasion, and metastasis. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, could inhibit stemness properties of cancer stem cells (CSCs) derived from TNBC cell in vitro and in vivo. This study is aimed at investigating whether lovastatin inhibits TNBC CSCs by inhibiting EMT and suppressing metastasis and the mechanism involved. In the present study, we found that lovastatin dysregulated lysine succinylation of cytoskeleton-associated proteins in CSCs derived from TNBC MDA-MB-231 cell. Lovastatin inhibited EMT as demonstrated by down-regulation of the protein levels of Vimentin and Twist in MDA-MB-231 CSCs in vitro and vivo and by reversal of TGF-ß1-induced morphological change in MCF10A cells. Lovastatin also inhibited the migration of MDA-MB-231 CSCs. The disruption of cytoskeleton in TNBC CSCs by lovastatin was demonstrated by the reduction of the number of pseudopodia and the relocation of F-actin cytoskeleton. Combination of lovastatin with doxorubicin synergistically inhibited liver metastasis of MDA-MB-231 CSCs. Bioinformatics analysis revealed that higher expression levels of cytoskeleton-associated genes were characteristic of TNBC and predicted survival outcomes in breast cancer patients. These data suggested that lovastatin could inhibit the EMT and metastasis of TNBC CSCs in vitro and in vivo through dysregulation of cytoskeleton-associated proteins.

6.
Biology (Basel) ; 10(5)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068010

RESUMO

A cutaneous squamous cell carcinoma (cSCC) derived from keratinocytes is the second most common cause of non-melanoma skin cancer. The accumulation of the mutational burden of genes and cellular DNA damage caused by the risk factors (e.g., exposure to ultraviolet radiation) contribute to the aberrant proliferation of keratinocytes and the formation of a cSCC. A cSCC encompasses a spectrum of diseases that range from recursor actinic keratosis (AK) and squamous cell carcinoma (SCC) in situ (SCCIS) to invasive cSCCs and further metastatic SCCs. Emerging evidence has revealed that lncRNAs are involved in the biological process of a cSCC. According to the ceRNA regulatory theory, lncRNAs act as natural miRNA sponges and interact with miRNA response elements, thereby regulating the mRNA expression of their down-stream targets. This study was designed to search for the potential lncRNAs that may become potential therapeutic targets or biomarkers of a cSCC. Considering the spirit of the study to be adequately justified, we collected microarray-based datasets of 19 cSCC tissues and 12 normal skin samples from the GEO database (GSE42677 and GSE45164). After screening the differentially expressed genes via a limma package, we identified 24 differentially expressed lncRNAs (DElncRNAs) and 3221 differentially expressed mRNAs (DEmRNAs). The miRcode, miRTarBase, miRDB and TargetScan databases were used to predict miRNAs that could interact with DElncRNAs and DEmRNAs. A total of 137 miRNA-lncRNA and 221 miRNA-mRNA pairs were retained in the ceRNA network, consisting of 31 miRNAs, 11 DElncRNAs and 155 DEmRNAs. For the functional analysis, the top enriched biological process was enhancer sequence-specific DNA binding in Gene Ontology (GO) terms. The FoxO signaling pathway, autophagy and cellular senescence were the top enrichment terms based on a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The combination of a STRING tool and Cytoscape software (plug-in MCODE) identified five core mRNAs and built a core mRNA-associated ceRNA network. The expression for five identified core mRNAs and their related nine lncRNAs was validated using the external dataset GSE7553. Finally, one lncRNA HLA-F-AS1 and three mRNAs named AGO4, E2F1 and CCND1 were validated with the same expression patterns. We speculate that lncRNA HLA-F-AS1 may sponge miR-17-5p or miR-20b-5p to regulate the expression of CCND1 and E2F1 in the cSCC. The present study may provide potential diagnostic and therapeutic targets for cSCC patients.

7.
Genomics ; 113(4): 1999-2009, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33915244

RESUMO

The high-quality reference-grade genome for Gossupium tomentosum can greatly promote the progress in biological research and introgression breeding for the mainly cultivated species, G. hirsutum. Here, we report a high-quality genome assembly for G. tomentosum by integrating PacBio and Hi-C technologies. Comparative genomic analysis revealed a large number of genetic variations. Two re-sequencing-based ultra-dense genetic maps were constructed which comprised 4,047,199 and 6,009,681 SNPs, 4120 and 4599 bins and covering 4126.36 cM and 4966.72 cM in the EMF2 (F2 from G. hirsutum × G. tomentosum) and GHF2 (F2 from G. hirsutum × G. barbadense). The EMF2 exhibited lower recombination rate at the whole-genome level as compared with GHF2. We mapped 22 and 33 QTL associated with crossover frequency and predicted Gh_MRE11 and Gh_FIGL1 as the candidate genes governing crossover in the EMF2 and GHF2, respectively. We identified 13 significant QTL that regulate the floral transition, and revealed that Gh_AGL18 was associated with the floral transition. Therefore, our study provides a valuable genomic resource to support a better understanding of cotton interspecific cross and recombination landscape for genetic improvement and breeding in cotton.

8.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1558-1563, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787154

RESUMO

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doença de Alzheimer/tratamento farmacológico , Mineração de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Prescrições
9.
J Mater Chem B ; 9(8): 2025-2032, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33555002

RESUMO

The usage of a guided bone regeneration (GBR) membrane that prevents the ingrowth of fibroblast cells and enhances the regeneration rate is an effective strategy for bone regeneration therapy. Herein, LAPONITE® (LAP) nanoplatelets, a bioactive clay with good osteoinductivity, were incorporated within a regenerated silk fibroin (RSF) microfibrous mat via electrospinning. The as-prepared RSF-LAP hybrid microfibrous mats had an interconnected structure with pore size significantly smaller than that of the fibroblast cells, leading to an effective prevention of fibroblast cell ingrowth into the defect sites. As per the water contact angle measurements, the incorporation of LAP significantly improved the hydrophilicity of the RSF microfibrous mats. The in vitro cell experiment results show that the RSF-LAP microfibrous mats exhibited better cell adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs) than the pristine RSF microfibrous mats. Moreover, the RSF-LAP microfibrous mats promoted osteogenic differentiation by upregulating alkaline phosphatase (ALP) activity and osteo-specific gene expression. Therefore, the results suggest that this easily fabricated LAP-incorporated RSF microfibrous mat has great potential to be a promising biomaterial for GBR applications.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Membranas Artificiais , Silicatos/química , Seda/química , Fosfatase Alcalina/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanoestruturas/química , Osteogênese/efeitos dos fármacos , Ratos
10.
Hepatology ; 73(5): 1671-1687, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33080074

RESUMO

BACKGROUND AND AIMS: Mucosal-associated invariant T (MAIT) cells are nonconventional T cells restricted to major histocompatibility complex class I-related protein 1 (MR1). They are highly abundant in human liver and activated by T-cell receptor (TCR)-dependent and TCR-independent mechanisms to exhibit rapid, innate-like effector responses. However, the roles of MAIT cells in chronic HBV infection are still open for study. This study aims to test their antiviral potential and investigate their dynamic changes and regulating factors during chronic HBV infection. APPROACH AND RESULTS: Blood samples from 257 chronic HBV-infected patients were enrolled, and nontumor liver specimens were collected from 58 HBV-infected HCC patients. Combining cell-culture experiments and human data, we showed that MAIT cells had strong cytotoxicity against HBV-transfected hepatocytes in an MR1-dependent way. However, circulating and hepatic MAIT cells in HBV-infected patients decreased significantly compared to controls. Correlation analysis suggested that MAIT cell frequency was associated with disease progression and inversely correlated with serum-conjugated bilirubin level. In particular, conjugated bilirubin not only directly promoted MAIT cell activation and apoptosis, but also impaired TCR-induced proliferation and expansion of MAIT cells, which could be partially rescued by IL-2 in the absence of conjugated bilirubin. Despite that MAIT cells from patients with high conjugated bilirubin levels showed decreased cytokine-producing capacity, the increased TCR-dependent antiviral cytokine production suggested MAIT cells as an important guardian of chronic HBV with high conjugated bilirubin. CONCLUSIONS: We reveal the MR1-dependent, anti-HBV potential of MAIT cells and identify conjugated bilirubin as a major factor dysregulating its frequency and function in chronic HBV-infected patients, suggesting a therapeutic target for MAIT-cell-based immunity against chronic HBV infection.

11.
Am J Physiol Heart Circ Physiol ; 320(1): H458-H468, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095054

RESUMO

Coronary artery spasm (CAS) is an intense vasoconstriction of coronary arteries that causes total or subtotal vessel occlusion. The cardioprotective effect of sirtuin-1 (SIRT1) has been extensively highlighted in coronary artery diseases. The aims within this study include the investigation of the molecular mechanism by which SIRT1 alleviates CAS. SIRT1 expression was first determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis in an endothelin-1 (ET-1)-induced rat CAS model. Interaction among SIRT1, nuclear factor-kappaB (NF-κB), myosin light chain kinase/myosin light chain-2 (MLCK/MLC2), and ET-1 was analyzed using luciferase reporter assay, RT-qPCR, and Western blot analysis. After ectopic expression and depletion experiments in vascular smooth muscle cells (VSMCs), contraction and proliferation of VSMCs and expression of contraction-related proteins (α-SMA, calponin, and SM22α) were measured by collagen gel contraction, 5-ethynyl-2'-deoxyuridine (EdU) assay, RT-qPCR, and Western blot analysis. The obtained results showed that SIRT1 expression was reduced in rat CAS models. However, overexpression of SIRT1 inhibited the contraction and proliferation of VSMCs in vitro. Mechanistic investigation indicated that SIRT1 inhibited NF-κB expression through deacetylation. Moreover, NF-κB could activate the MLCK/MLC2 pathway and upregulate ET-1 expression by binding to their promoter regions, thus inducing VSMC contraction and proliferation in vitro. In vivo experimental results also revealed that SIRT1 alleviated CAS through regulation of the NF-κB/MLCK/MLC2/ET-1 signaling axis. Collectively, our data suggested that SIRT1 could mediate the deacetylation of NF-κB, disrupt the MLCK/MLC2 pathway, and inhibit the expression of ET-1 to relieve CAS, providing a theoretical basis for the prospect of CAS treatment and prevention.NEW & NOTEWORTHY Rat coronary artery spasm models exhibit reduced expression of SIRT1. Overexpression of SIRT1 inhibits contraction and proliferation of VSMCs. SIRT1 inhibits NF-κB through deacetylation to modulate VSMC contraction and proliferation. NF-κB activates the MLCK/MLC2 pathway. NF-κB upregulates ET-1 to modulate VSMC contraction and proliferation.


Assuntos
Miosinas Cardíacas/metabolismo , Vasoespasmo Coronário/prevenção & controle , Endotelina-1/metabolismo , Músculo Liso Vascular/enzimologia , Cadeias Leves de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Vasoconstrição , Acetilação , Animais , Proliferação de Células , Forma Celular , Células Cultivadas , Vasoespasmo Coronário/enzimologia , Vasoespasmo Coronário/genética , Vasoespasmo Coronário/fisiopatologia , Vasos Coronários/enzimologia , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Masculino , Músculo Liso Vascular/fisiopatologia , NF-kappa B/genética , Ratos Nus , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1/genética
12.
Epigenomics ; 12(17): 1501-1513, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32901506

RESUMO

Aim: Alzheimer's disease (AD) is the most frequent cause of dementia and characterized by the accumulation of ß-amyloid peptides in plaques and vessel walls. This study proposed a hypothesis of an inhibitory role of miR-96-5p in AD via regulating Foxo1. Methods & methods: AD mouse models were established by injecting with 1% pentobarbital. Results: Knockdown of miR-96-5p in the presence of naringin was shown to reduce the expression of Foxo1 and contents of superoxide dismutase, catalase and glutathione peroxidase, yet increase lipocalin-2 expression as well as hydroxyproline and malondialdehyde contents. Also, Foxo1-mediated lipocalin-2 inhibition attenuated AD. Conclusion: Our study shows downregulating miR-96-5p limited AD progression, highlighting miR-96-5p a potential therapeutic target in treating AD.

13.
Int Immunopharmacol ; 84: 106518, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32380408

RESUMO

BACKGROUND: Despite knowledge regarding the effects of antioxidants in ameliorating oxidative damage, evidence concerning their effects on activated immune cells is lacking. Here, a concanavalin A (Con A)-induced hepatitis mouse model was used to investigate the protective effects and immune regulatory mechanisms of mitochondrial-targeted ubiquinone (MitoQ). METHODS: Wild-type (WT) and CD1d-knockout (CD1d-/-, NKT cell deficient) mice were pretreated with MitoQ and then intravenously injected with a sublethal dose of Con A. Serum transaminase and inflammatory cytokine levels were tested. Immune cell functions and AMPK/mTORC1 pathway activation in liver tissue were also evaluated. RESULTS: NKT cells were critical for extensive pro-inflammatory cytokine production and prolonged liver injury upon Con A challenge, while IFN-γ-producing non-NKT cells played an important role during the hyperacute phase. MitoQ treatment not only ameliorated NKT cell-independent hyperacute hepatitis within 12 h post Con A administration but also alleviated NKT cell-dependent extended liver injury at 24 h. The underlying mechanisms involved an inhibition of the heightened activation of iNKT cells and conventional T cells, suppression of the excessive production of IFN-γ, TNF-α and IL-6, and modulation of aberrant AMPK and mTORC1 pathways. CONCLUSION: MitoQ efficiently alleviates Con A-induced hepatitis through immune regulation, suggesting a new therapeutic approach for immune-mediated liver injury by targeting mitochondrial ROS.


Assuntos
Antioxidantes/uso terapêutico , Hepatite/tratamento farmacológico , Compostos Organofosforados/uso terapêutico , Ubiquinona/análogos & derivados , Proteínas Quinases Ativadas por AMP/imunologia , Animais , Antígenos CD1d/genética , Antioxidantes/farmacologia , Concanavalina A , Citocinas/imunologia , Feminino , Hepatite/imunologia , Imunomodulação/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/imunologia , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/imunologia , Compostos Organofosforados/farmacologia , Espécies Reativas de Oxigênio/imunologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
14.
J Cancer ; 11(13): 3713-3716, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328175

RESUMO

Effective treatment modality for triple-negative breast cancer (TNBC) is currently lacking due to the absence of defined receptor targets. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, can selectively inhibit TNBC by targeting cancer stem cells in vivo and in vitro. Interestingly, we found that lovastatin induced the reappearance of human epidermal growth factor receptor 2 (HER2), one of the triple receptors that are missing in TNBC. This prompted us to explore the possibility of regaining sensitivity of TNBC cancer stem cells to receptor tyrosine kinase-targeting drugs. We found that while the combination of lovastatin with a HER2 inhibitor was not sufficient to show synergism, addition of an epidermal growth factor receptor (EGFR/HER1) inhibitor to this combination resulted in significant synergistic inhibitory effect on cell viability. Our findings provide a potential novel strategy of designing a cocktail composed of a lipid-lowering drug and two receptor tyrosine kinase inhibitors for the treatment of TNBC.

15.
IUBMB Life ; 72(2): 198-213, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31444954

RESUMO

Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA-135b (miR-135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR-135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR-135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR-135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR-135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR-135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR-135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR-135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR.


Assuntos
Aterosclerose/fisiopatologia , Autofagia , Modelos Animais de Doenças , Macrófagos/patologia , MicroRNAs/genética , Placa Aterosclerótica/patologia , Receptores da Eritropoetina/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Eritropoetina/genética
16.
Int J Biol Macromol ; 155: 1468-1477, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751749

RESUMO

In this work, silica nanoparticles modified with a new N-halamine precursor (EBDMH-SiO2 NPs) were synthesized through immobilization of 3-(4'-epoxyethyl-benzyl)-5,5-dimethylhydantoin (EBDMH) on the surface of amino-functionalized silica NPs. Then, EBDMH-SiO2 NPs and poly(lactic acid) (PLA) were blended at 185 °C to prepare a novel environmentally friendly PLA based nanocomposite (PLA/EBDMH-SiO2). The addition of EBDMH-SiO2 NPs has great influences on the thermal properties of nanocomposite. DSC results show that the grass transition temperature (Tg), cold crystallization temperature (Tcc) and melting temperature (Tm) of PLA in nanocomposites gradually decrease with the increase of EBDMH-SiO2 NPs contents up to 5%. After that, further rise in EBDMH-SiO2 NPs content actually increases Tg, Tcc, and Tm. The overall crystallization and spherulite growth rate of PLA show the similar trend. Furthermore, the introduction of EBDMH-SiO2 NPs increases the storage modulus and viscosity of the melt of nanocomposite, providing an additional benefit for PLA blowing and injection molding. After chlorination, the N-halamine precursors on the nanocomposite surfaces are transformed into N-halamines, which provide strong antibacterial activities against E. coli (CMCC 44103) and S. aureus (ATCC 6538), pointing to good potentials of the PLA/EBDMH-SiO2 nanocomposites for antibacterial applications including food packaging, filters, and a wide range of hygienic products.


Assuntos
Aminas/química , Antibacterianos/química , Antibacterianos/farmacologia , Poliésteres/química , Poliésteres/farmacologia , Dióxido de Silício/química , Nanocompostos/química , Viscosidade
17.
Nanoscale Res Lett ; 14(1): 314, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520223

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to drug resistance and difficult to treat. In this study, we grafted water-soluble pullulan with lovastatin (LV) to develop a novel amphiphilic conjugate, pullulan-encapsulated LV (PLV). The PLV conjugate was synthesized with three different ratios of pullulan to LV and characterized by Fourier transform infrared (FTIR). The degree of substitution (DS) of LV in terms of molar ratio was 7.87%, 3.58%, and 3.06% for PLV (1/2), PLV (1/3), and PLV (1/4), respectively, by proton NMR analysis. We selected the PLV (1/2) conjugate to prepare doxorubicin (DXR)-loaded PLV nanoparticles (PLV/DXR NPs) because of its superior properties. The average size and zeta potential for PLV (1/2) NPs were 177.6 nm and - 11.66 mV, respectively, determined by dynamic light scattering, and those for PLV/DXR NPs were 225.6 nm and - 10.51 mV, respectively. In vitro drug release profiling showed that PLV/DXR NPs sustainably released DXR within 72 h, which was more robust at pH 5.4 (97.90%) than pH 7.4 (76.15%). In the cytotoxicity study, PLV/DXR NPs showed greater inhibition of proliferation of TNBC MDA-MB-231 than non-TNBC MDA-MB-453 cells (IC50 0.60 vs 11.05 µM). FITC-loaded PLV/DXR NPs were prepared to investigate cellular uptake: both cell lines showed a time-dependent uptake of NPs, but the number of NPs entering MDA-MB-231 cells was greater than that entering the MDA-MB-453 cells. Pullulan-based NP co-delivery of LV and DXR could efficiently inhibit TNBC cells, which may help in designing a powerful drug delivery system for treating TNBC.

18.
Environ Sci Pollut Res Int ; 26(28): 29379-29387, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396877

RESUMO

It aimed to investigate and evaluate the soil amelioration process of bauxite residues with the amendments of organic materials from different sources. Wheat straw, poultry manure compost, and biosolids were chosen as the added organic materials. A series of essential soil properties were analyzed to evaluate the effects of organic materials on the soil amelioration of bauxite residue. The results indicated that organic amendments could obviously improve the texture of bauxite residues by increasing large aggregates contents, and elevating its organic matter content and fertility level (such as TN and TP). At the same time, organic additions were effective in reducing bauxite residues' salinity as pH, electrical conductivity and sodium content were obviously decreased in all rehabilitated treatments in comparison with control treatment. These improvements created sufficient conditions for a quick recovery of microbial communities in bauxite residues matrix. The maximum microbial biomass C increased to 0.642 g-C·kg-1, and the activities of urease, catalase, and invertase were massively elevated, especially for those after a year of rehabilitation, although alkali-phosphatase was kept a less level compared with other biological parameters. The further principal analysis and cluster analysis indicated that after 1 year of organic amendment, the improved bauxite residues matrix was very close to the reference soil based on the measured soil microbial properties. All the results suggested that organic amendment is an effective way to stimulate the soil amelioration of bauxite residues, and among the three amended organic materials, wheat straw and biosolid were better in improving the abiotic environmental conditions as well as biotic function recovery in soil amelioration of bauxite residue.


Assuntos
Óxido de Alumínio/química , Poaceae/química , Solo/química , Biomassa , Compostagem , Esterco , Microbiologia do Solo
19.
J Parasitol ; 105(1): 92-101, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30807720

RESUMO

Ticks are important vectors and reservoirs of several zoonotic pathogens. Recently, both known and unknown tick-borne pathogens have emerged and re-emerged, causing unpredictable epidemics. In this study, 211 soft tick samples were collected from Tongliao and Alxa in Inner Mongolia, China. Tick species were identified by morphological and molecular biological analyses. Morphological analysis showed that there was no significant difference in surface features between ticks from the 2 areas. Cloning by polymerase chain reaction (PCR) and sequencing of the 16S rRNA gene showed that all ticks belonged to the species Argas persicus. Analysis using Genetyx software indicated that there was a limited degree of diversity between ticks from the 2 areas. Three base changes were detected in the 16S rRNA gene. We constructed phylogenetic trees using MEGA 6.0 software and showed that the ticks from the 2 areas might have evolved independently from species in other geographical areas. To assess the presence of Rickettsia, Streptococcus suis, and Staphylococcus aureus pathogens in tick samples, over 100 16S rRNA sequences belonging to these 3 pathogens were obtained from GenBank. We used CLC Sequence Viewer 7.0 to determine conserved sequences for the design of degenerate primers. Using standard PCR, we detected Rickettsia-specific genes, including 16S rRNA, 17KD, and ompB, in gDNA samples of ticks from Alxa. This study has laid a foundation for future studies on the biodiversity of ticks and for a new pathogen information database of ticks in local areas.


Assuntos
Argas/classificação , Argas/genética , Animais , Argas/anatomia & histologia , Argas/microbiologia , Galinhas , China , Clonagem Molecular , DNA/química , DNA/isolamento & purificação , Feminino , Variação Genética , Genótipo , Abrigo para Animais , Funções Verossimilhança , Masculino , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo Genético , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
20.
Chin J Integr Med ; 25(2): 87-90, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30796688

RESUMO

The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with the development of science and technology, Western medicine, or modern medicine, was born through experimental analysis and research. With the development of medicine, the pros and cons of both medical systems become increasingly evident. How to integrate them and learn from each other will be the direction of future development of medicine. The formation and development of integrated medicine will, inevitably, usher in a new era for medicine.


Assuntos
Medicina Integrativa , Medicina Tradicional Chinesa , Corpo Humano , Humanos , Modelos Teóricos
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