Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 121
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Curr Pharm Des ; 25(24): 2609-2625, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603055

RESUMO

The conventional Drug Delivery System (DDS) has limitations such as leakage of the drug, toxicity to normal cells and loss of drug efficiency, while the stimuli-responsive DDS is non-toxic to cells, avoiding the leakage and degradation of the drug because of its targeted drug delivery to the pathological site. Thus nanomaterial chemistry enables - the development of smart stimuli-responsive DDS over the conventional DDS. Stimuliresponsive DDS ensures spatial or temporal, on-demand drug delivery to the targeted cancer cells. The DDS is engineered by using the organic (synthetic polymers, liposomes, peptides, aptamer, micelles, dendrimers) and inorganic (zinc oxide, gold, magnetic, quantum dots, metal oxides) materials. Principally, these nanocarriers release the drug at the targeted cells in response to external and internal stimuli such as temperature, light, ultrasound and magnetic field, pH value, redox potential (glutathione), and enzyme. The multi-stimuli responsive DDS is more promising than the single stimuli-responsive DDS in cancer therapy, and it extensively increases drug release and accumulation in the targeted cancer cells, resulting in better tumor cell ablation. In this regard, a handful of multi-stimuli responsive DDS is in clinical trials for further approval. A comprehensive review is crucial for addressing the existing knowledge about multi-stimuli responsive DDS, and hence, we summarized the emerging strategies in tailored ligand functionalized stimuli-responsive nanocarriers as the DDS for cancer therapies.

2.
Exp Cell Res ; 384(1): 111545, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31470016

RESUMO

Cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD) and dampens antiviral response, which increases viral infections and leads to COPD acute exacerbation (AECOPD). Adenovirus, a nonenveloped DNA virus, is linked with AECOPD, whose DNAs trigger innate immune response via interacting with pattern recognition receptors (PRRs). Stimulator of interferon genes (STING), as a cytosolic DNA sensor, participates in adenovirus-induced interferon ß (IFNß)-dependent antiviral response. STING is involved in various pulmonary diseases, but role of STING in pathogenesis of AECOPD is not well documented. In the present study, we explored relationship between STING and AECOPD induced by recombinant adenovirus vectors (rAdVs) and CS in wild type (WT) and STING-/- mice; and also characterized the inhibition of STING- IFNß pathway in pulmonary epithelium exposed to cigarette smoke extract (CSE). We found that CS or CSE exposure alone dramatically inhibited STING expression, but not significantly effected IFNß production. Moreover, CS or CSE-exposed significantly suppressed activation of STING-IFNß pathway induced by rAdVs and suppressed clearance of rAdVs DNA. Inflammation, fibrosis and emphysema of lung tissues were exaggerated when treated with CS plus rAdVs, which further deteriorate in absences of STING. In A549 cells with knockdown of STING, we also observed enhancing apoptosis related to emphysema, especially CSE and adenovirus vectors in combination. Therefore, STING may play a protective role in preventing the progress of COPD.

3.
J Nat Prod ; 82(8): 2337-2342, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31381332

RESUMO

AntiSMASH analysis of genome DNA of Streptomyces CPCC 204980, a soil isolate with potent antibacterial activity, revealed a gene cluster for polycyclic xanthones. A subsequent chemical study confirmed that the microorganism produced polycyclic xanthone cervinomycin A2 (1) and the new congeners cervinomycins B1-4 (2-5). The structures of 1-5 were determined by comprehensive analyses of MS and NMR data, which indicated that 2-5 featured a common dihydro-D ring in the polycyclic xanthone core moiety of their molecules. 2-5 are toxic to human cancer cells and active against Gram-positive bacteria.

4.
Life Sci Alliance ; 2(4)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31371524

RESUMO

Centromeric chromatin in fission yeast is distinguished by the presence of nucleosomes containing the histone H3 variant Cnp1CENP-A Cell cycle-specific deposition of Cnp1 requires the Mis16-Mis18-Mis19 complex, which is thought to direct recruitment of Scm3-chaperoned Cnp1/histone H4 dimers to DNA. Here, we present the structure of the essential Mis18 partner protein Mis19 and describe its interaction with Mis16, revealing a bipartite-binding site. We provide data on the stoichiometry and overall architecture of the complex and provide detailed insights into the Mis18-Mis19 interface.

5.
Chest ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31398348

RESUMO

BACKGROUND: Aspiration-related lung diseases are commonly diagnosed presumptively based on the clinical context and radiologic findings. Limited data exist on the spectrum of clinico-radiologic presentations associated with aspiration. METHODS: This study reviewed all cases of aspiration identified on lung biopsy encountered at the Mayo Clinic between 2003 and 2017. Demographic and clinical features, including risk factors for aspiration, diagnoses suspected prior to biopsy, imaging findings, and microbiologic data, were analyzed. RESULTS: A total of 52 consecutive adult cases of aspiration identified on lung biopsy (histologic presence of food or other particulate matter) were included; patients' median age was 59 years (range, 22 to 79 years), 38% were women, and there were five lung transplant recipients. Of these, 63% were diagnosed according to results of surgical biopsy (including four cases of lobectomy) and 37% according to results of transbronchial biopsy. Aspiration was clinically suspected prior to biopsy in 35% of the subjects. Ninety percent of subjects had at least one identifiable risk factor for aspiration; gastroesophageal reflux disease was the most common (62%), followed by a structurally abnormal esophagogastric tract and the use of consciousness-impairing medications. Only 27% of patients reported dysphagia or choking. Chest CT imaging revealed a variety of parenchymal patterns, including bronchiolitis (42%), patchy consolidation (19%), and mass (15%). Of 25 patients undergoing a video-swallow evaluation, 14 (56%) had abnormal results with laryngeal penetration with or without aspiration. Microbial cultures obtained in 21 lung biopsy specimens yielded no pathogens. CONCLUSIONS: Aspiration can occur in the absence of subjective or demonstrable swallowing difficulties and manifest a broad spectrum of clinico-radiologic presentations.

6.
Int J Cardiol ; 296: 129-135, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439425

RESUMO

BACKGROUND: The therapeutic potential of doxorubicin (DOX) is limited by cardiotoxicity. Rubicon is an inhibitory interacting partner of autophagy protein UVRAG. Currently, the role of Rubicon in DOX-induced cardiotoxicity is unknown. In this study, we test the hypothesis that loss of Rubicon attenuates DOX-induced cardiotoxicity. METHODS: A mouse model of acute DOX-induced cardiotoxicity was established by a single intraperitoneal injection of DOX at a dose of 20 mg/kg. Rubicon expression was detected by Western blot. Cardiac damage was determined by measuring activities of lactate dehydrogenase and myocardial muscle creatine kinase in the serum, cytoplasmic vacuolization, collagen deposition, ROS levels, ATP content and mitochondrial damage in the heart. Cardiac morphometry and function were assessed by echocardiography. Markers for autophagy, mitophagy and mitochondrial dynamics were evaluated by Western blot and real time reverse transcription polymerase chain reaction. RESULTS: Rubicon expression was reduced in the heart 16 h after DOX treatment. DOX induced accumulation of cytoplasmic vacuolization and collagen, increased serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, enhanced ROS levels, reduced ATP content, pronounced mitochondrial damage and greater left ventricular wall thickness in wild type mice, which were mitigated by Rubicon deficiency. Mechanistically, loss of Rubicon improved DOX-induced impairment of autophagic flux, Parkin-mediated mitophagy and mitochondrial fission and fusion in the heart. CONCLUSIONS: Loss of Rubicon ameliorates DOX-induced cardiotoxicity through enhancement of mitochondrial quality by improving autophagic flux, mitophagy and mitochondrial dynamics. Rubicon is a potential molecular target for prevention and therapy of DOX cardiotoxicity.

7.
Technol Cancer Res Treat ; 18: 1533033819846638, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311442

RESUMO

OBJECTIVE: In this study, we aimed to clarify the effects of long noncoding ribonucleic acid prostrate androgen-regulated transcript-1 on bladder cancer cell proliferation and apoptosis. METHODS: Microarrays were implemented to investigate the long noncoding ribonucleic acid expression profiles in bladder cancer tissue (N = 9) and in noncancer bladder tissue (N = 5). Relative prostrate androgen-regulated transcript-1 expression levels in tissue samples or cell lines were detected by real-time quantitative reverse transcription-polymerase chain reaction. Prostrate androgen-regulated transcript-1 expression was enhanced by the transfection of pcDNA3.1-prostrate androgen-regulated transcript-1 and downregulated by the infection with pcMV-sh prostrate androgen-regulated transcript-1. Additionally, cell proliferation and apoptosis were measured by the cell counting kit-8 assay and flow cytometry, respectively. Cell invasion was determined by a Transwell assay. RESULTS: Prostrate androgen-regulated transcript-1 expression was upregulated in bladder cancer tissues compared to adjacent nontumor tissues. Furthermore, prostrate androgen-regulated transcript-1 levels were successfully upregulated by pcDNA3.1-prostrate androgen-regulated transcript-1 and depleted by pCMV-sh prostrate androgen-regulated transcript-1 in bladder cancer cell lines (5637, T24). Enhanced prostrate androgen-regulated transcript-1 expression promoted cell proliferation and invasion and inhibited cell apoptosis. However, knockdown of prostrate androgen-regulated transcript-1 expression inhibited cell proliferation and invasion and induced cell apoptosis. CONCLUSION: In summary, these data suggest that the knockdown of prostrate androgen-regulated transcript-1 represents a tumor suppressor player in bladder cancer and contributes to the inhibition of tumor proliferation, the promotion of cell apoptosis, and the suppression of cell invasion. Prostrate androgen-regulated transcript-1 may function as a new prognostic biomarker and as a feasible therapeutic target for patients with bladder cancer.

8.
Arch Biochem Biophys ; 671: 143-151, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31283911

RESUMO

Aptamer based drug delivery systems are gaining the importance in anticancer therapy due to their targeted drug delivery efficiency without harming the normal cells. The present work formulated the pH-dependent aptamer functionalized polymer-based drug delivery system against human lung cancer. The prepared aptamer functionalized doxorubicin (DOX) loaded poly (D, L-lactic-co-glycolic acid) (PLGA), poly (N-vinylpyrrolidone) (PVP) nanoparticles (APT-DOX-PLGA-PVP NPs) were spherical in shape with an average size of 87.168 nm. The crystallography and presence of the PLGA (poly (D, L-lactic-co-glycolic acid)) and DOX (doxorubicin) in APT-DOX-PLGA-PVP NPs were indicated by the X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FTIR), and 1H and 13C nuclear magnetic resonance spectrometer (NMR). The pH-dependent aptamer AS1411 based drug release triggered the cancer cell death was evidenced by cytotoxicity assay, flow cytometry, and fluorescent microscopic imaging. In addition, the cellular uptake of the DOX was determined and the apoptosis-related signaling pathway in the A549 cells was studied by Western blot analysis. Further, the in vivo study revealed that mice treated with APT-DOX-PLGA-PVP NPs were significantly recovered from cancer as evident by mice weight and tumor size followed by the histopathological study. It was reported that the APT-DOX-PLGA-PVP NPs induced the apoptosis through the activation of the apoptosis-related proteins. Hence, the present study revealed that the APT-DOX-PLGA-PVP NPs improved the therapeutic efficiency through the nucleolin receptor endocytosis targeted drug release.

9.
Int J Nanomedicine ; 14: 3427-3438, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190801

RESUMO

Background: Biogenic silver nanoparticles (AgNPs) have wider range of biomedical applications. The present work synthesized Tp-AgNPs using mycelial extract of endophytic fungus Talaromyces purpureogenus (MEEF), characterized, and analyzed for antibacterial, anti-proliferation and cell wounding healing activities. Methods: The synthesized Tp-AgNPs were characterized by UV-visible spectrophotometer (UV-Vis), field emission transmission electron microscopy (FETEM) with energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), particle size analysis (PSA) and X-ray diffraction (XRD). Further, antibacterial activity was determined by Kirby-Bauer test and anti-proliferation activity was tested in human lung carcinoma A549 by water-soluble tetrazolium and flow cytometer assay. In addition, cell wounding healing activity was determined by scratch assay. Results: UV-Vis results displayed a strong absorption peak from 390 nm to 420 nm, which indicated the successful synthesis of Tp-AgNPs. FETEM-EDS results indicated the round and triangle shaped Tp-AgNPs with the average size of 25 nm in accordance with PSA. FTIR analysis indicated the involvement of various functional molecules from MEEF in the synthesis of Tp-AgNPs. XRD result proved nature of Tp-AgNPs as a high-quality crystal. The Tp-AgNPs significantly inhibited the growth of bacterial pathogens at the minimal inhibitory concentration of 16.12 µg.mL-1 for Gram+, and 13.98 µg.mL-1 for Gram- bacteria. Further, Tp-AgNPs (2 µg.mL-1) showed a strong anti-proliferation effect in A549. Interestingly, Tp-AgNPs was not cytotoxic to normal NIH3T3 cells. In addition, the NPs exhibited a strong cell wounding healing activity. Conclusion: This work biosynthesized AgNPs with strong antibacterial, anticancer and cell wound healing properties using endophytic fungus T. purpureogenus.


Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Prata/farmacologia , Talaromyces/metabolismo , Células A549 , Animais , Bactérias/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Nanopartículas Metálicas/ultraestrutura , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Prata/química , Cicatrização/efeitos dos fármacos
10.
Molecules ; 24(12)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31248172

RESUMO

Actinosynnema is a small but well-known genus of actinomycetes for production of ansamitocin, the payload component of antibody-drug conjugates against cancers. However, the secondary metabolite production profile of Actinosynnema pretiosum ATCC 31565, the most famous producer of ansamitocin, has never been fully explored. Our antiSMASH analysis of the genomic DNA of Actinosynnema pretiosum ATCC 31565 revealed a NRPS-PKS gene cluster for polyene macrolactam. The gene cluster is very similar to gene clusters for mirilactam and salinilactam, two 26-membered polyene macrolactams from Actinosynnema mirum and Salinispora tropica, respectively. Guided by this bioinformatics prediction, we characterized a novel 26-membered polyene macrolactam from Actinosynnema pretiosum ATCC 31565 and designated it pretilactam. The structure of pretilactam was elucidated by a comprehensive analysis of HRMS, 1D and 2D-NMR, with absolute configuration of chiral carbons predicted bioinformatically. Pretilactam features a dihydroxy tetrahydropyran moiety, and has a hexaene unit and a diene unit as its polyene system. A preliminary antibacterial assay indicated that pretilactam is inactive against Bacillus subtilis and Candida albicans.

11.
Psychiatry Res ; 273: 782-787, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31207866

RESUMO

Evidence indicates that abnormal phospholipase A2 (PLA2) levels and niacin insensitivity are present in individuals with schizophrenia. This study was designed to determine whether differences in plasma calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) exist between those with schizophrenia and healthy controls, and to explore the correlation between PLA2s and the niacin skin reaction in schizophrenic patients. We performed ELISA experiments to measure the concentrations of plasma iPLA2 and cPLA2 and we conducted a series of niacin skin tests on schizophrenic patients from the Chinese Han population. In addition, a meta-analysis of the relationship between PLA2 and schizophrenia was conducted. The plasma concentration of iPLA2 in patients with schizophrenia was significantly higher than that in healthy controls while the plasma concentration of cPLA2 did not differ. The meta-analysis also revealed that the activity level of iPLA2 in individuals with schizophrenia was higher than that in healthy controls, whereas that of cPLA2 was not. Furthermore, a significant positive correlation was found between the concentration of iPLA2 and the score for the skin flushing response within 20 min. The abnormal plasma iPLA2 concentration and its relationship with the niacin skin test in schizophrenic patients has contributed to a deeper understanding of the pathology of schizophrenia, which may in turn provide new insights into the clinical diagnoses and treatment of schizophrenia.

12.
Opt Express ; 27(9): 13516-13525, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31052872

RESUMO

In this study, we fabricated a temperature-responsive infrared reflector that adjusts to temperature changes by changing its transmittance of incident IR light. The device utilized a thermally induced change in the pitch of a cholesteric liquid crystal (CLC) to achieve near-infrared light reflection in a particular wavelength range. In addition, a polymer-stabilized cholesteric liquid crystal (PSCLC) was used as an alternative to further optimize the device performance. Polyethylene terephthalate (PET) was used as the substrate material to allow the reflector to be flexible. The light transmission performance of the reflector at different bending angles was explored, and no significant effect was found. A simulated solar device was established to study the temperature regulation effects of both CLC and PSCLC devices.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(6): 584-587, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31055811

RESUMO

OBJECTIVE: To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey. METHODS: Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members. RESULTS: Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet. CONCLUSION: The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.


Assuntos
Proteínas/genética , Paraplegia Espástica Hereditária , Adulto , Grupo com Ancestrais do Continente Asiático , Heterozigoto , Humanos , Mutação , Linhagem , Fenótipo , Paraplegia Espástica Hereditária/genética
14.
Antioxid Redox Signal ; 31(8): 579-588, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31126188

RESUMO

Although several underlying etiologic implications for schizophrenia (SZ) have been proposed, the cross talk between them is rarely explored systematically. The aim of the present study was to illustrate the pathogenic mechanism of SZ through describing a systematical pathophysiology network using proteomic signatures in first-episode SZ patients. A total of 3152 proteins were identified in leukocytes, and 475 of these proteins were significantly altered in SZ. Functional analysis revealed that cell redox homeostasis was dramatically disrupted, demonstrated as upregulated glycolysis, mitochondrial oxidative phosphorylation, and thioredoxin-centered antioxidant system. We also identified an activated complement system and caspase-independent apoptosis. In addition, increased pyruvate and lactate levels and decreased lactate-to-pyruvate ratios were observed in plasma of SZ patients. The results here lead to the hypothesis that increased oxidative stress is caused by metabolic upregulation and complement activation, which induces protein damage and cell apoptosis, thus contributing to the development of SZ. Antioxid. Redox Signal. 31, 579-588.

15.
Biomolecules ; 9(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934938

RESUMO

This work tested antioxidant, anti-lung cancer, and antibacterial activities by in vitro, in vivo, and computational experiments for the metabolites extracted from the bark, seed, and stem of Toxicodendron vernicifluum. The results showed that all the extracts significantly scavenged 1,2-diphenyl-1-picrylhydrazyl (DPPH) in a dose-dependent manner. But, the total phenol content (TPC) ranged from 2.12 to 89.25% and total flavonoids content (TFC) ranged from 1.02 to 15.62% in the extracts. The methanolic bark extract (MBE) exhibited higher DPPH scavenging activity than the other extracts, probably due to the higher content of the TPC and TFC present in it. Among the extracts, only the MBE showed anti-lung cancer activity at an acceptable level with a therapeutic index value (22.26) against human lung carcinoma. This was due to the cancer cell death in A549 induced by MBE through reactive oxygen species (ROS) generation, apoptosis, and cell arrest in G1 phase and inhibition of anti-pro-apoptotic protein survivin. Among the extracts, MBE showed significantly higher antibacterial activity as evident through the higher zone of inhibition 13 ± 0.5 mm against methycilin resistant strain of Staphylococcus aureus (MRSA), Salmonila enteria subp. enterica, and P. aeruginosa, 11 ± 0.3 mm against E. coli and 10 ± 0.2 mm against B. cereus. The MBE also showed an excellent antibacterial activity with lower minimal inhibitory concentration (MIC). Particularly, the MBE showed more significant antibacterial activity in MRSA. The in vivo antibacterial activity of the MBE was further tested in C. elegans model. The treatment of the MRSA induced cell disruption, damage and increased mortality of C. elegans as compared to the untreated and MBE treated C. elegans with normal OP50 diet. Moreover, the MBE treatment enhanced the survival of the MRSA infected C. elegans. The compounds, such as 2,3,3-trimethyl-Octane and benzoic from the MBE, metabolized the novel bacterial topoisomerases inhibitor (NBTI) and MRSA related protein (PBP2a). Overall the T. vernicifluum is potentially bioactive as evident by antioxidant, anti-lung cancer, and antibacterial assays. Further studies were targeted on the purification of the novel compounds for the clinical evaluation.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Picratos/antagonistas & inibidores , Toxicodendron/química , Células A549 , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Caenorhabditis elegans/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Neoplasias Pulmonares/patologia , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
16.
PLoS One ; 14(4): e0214335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30934009

RESUMO

The rubber tree (Hevea brasiliensis Muell. Arg.) is a rubber producing crop and contains specialized laticifers. MADS-box genes are a family of transcription factor genes that regulate plant development, especially floral organ and gametophyte development. 97 MADS-box genes were identified in the rubber tree through transcriptomes and genome mining. 93.8% of the genes were mapped onto the genome scaffolds in correspondence to the coverage (93.8%) of current version of sequenced genome. Phylogenetic analysis indicates that type II MADS-box genes have been more actively duplicated than their orthologous genes in Arabidopsis and rice, so that most (70, 72.2%) of the MADS-box genes in the rubber tree belong to type II subfamily. This is a high percentage compared to those in Arabidopsis (43.7%) and rice (56.8%). Moreover, 69 out of 70 type II genes in the rubber tree are transcribed, and they are mostly predominantly expressed in flowers, but some genes are predominantly expressed in laticifers, suggesting their roles in both flower and laticifer development. The number of type I genes in the rubber tree is only 27 (27.8%), a much smaller number compared to their orthologous genes in Arabidopsis (56.3%) and rice (43.2%). At the same time, most of the type I genes (55.6%, 15) in the rubber tree are silent and are probably pseudogenes. The high birth rate and low death rate of type II genes and low birth rate and high death rate of type I genes may corresponds to special developmental requirements in the rubber tree, e.g. the development of laticifer system for biosynthesis of cis-polyisoprene, the rubber. Moreover, atypical MIKC* factors (e.g. HbMADS1 in S-clade, and HbMADS20 in P-clade) are identified. These genes are diverged to typical MIKC* genes in sequences and facilitate functions required in laticifer development and rubber biosynthesis, which is not necessary in Arabidopsis and rice.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30974818

RESUMO

Although previous research has documented a host of negative consequences of job insecurity, workplace interpersonal relationships have rarely been considered. This omission might be caused by the application of broad stress theories to the job insecurity literature without taking a nuanced perspective to understand the nature of job insecurity. To address this issue, we conceptualized job insecurity as a threat to employee social acceptance by their employer. This conceptualization, therefore, allows us to apply the multimotive model of social rejection to investigate a previously-overlooked outcome of job insecurity-workplace friendships. Specifically, we investigated the relationship between both job feature insecurity and job loss insecurity with workplace friendships. Based on stress coping theory and the fundamental differences between job feature insecurity and job loss insecurity, we further proposed that employees' tendency to engage in positive gossip buffers the negative impact of job feature insecurity on workplace friendships, whereas employees' tendency to engage in negative gossip buffers the negative impact of job loss insecurity on workplace friendships. Data collected from 286 working adults from Mturk supported our hypotheses. Our study opens the door for future research to take a more nuanced approach when examining nontraditional consequences of job insecurity.


Assuntos
Comunicação , Amigos/psicologia , Satisfação no Emprego , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade
18.
Nanotoxicology ; 13(3): 354-368, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30704318

RESUMO

Nanomaterials are widely used in an ever-increasing number of consumer and industrial products. It is therefore essential that the toxic effects of nanomaterials are understood in order to improve product safety. Here we evaluate the toxicity of inhaled halloysite nanotubes (HNTs) by applying a purpose designed inhalation exposure system and succeed in suppressing HNTs toxicity using trehalose. By assessing apoptosis, oxidative stress, inflammatory response, and autophagy, it is found that HNTs can cause sub-chronic toxicity in mice. Further investigations indicate that HNTs induce autophagy blockade that results in the accumulation of sequestosome-1 (p62), which is responsible for the excessive apoptosis, inflammatory response and oxidative stress. We found that p62 can be eliminated by trehalose and the application of trehalose in vitro and in vivo successfully inhibits toxicity by accelerating the clearance of p62. Trehalose shows great potential for reducing nanoparticle toxicity.

19.
Nat Commun ; 10(1): 733, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760718

RESUMO

A growing emphasis in anticancer drug discovery efforts has been on targeting histone acetylation modulators. Here we comprehensively analyze the genomic alterations of the genes encoding histone acetylation modulator proteins (HAMPs) in the Cancer Genome Atlas cohort and observe that HAMPs have a high frequency of focal copy number alterations and recurrent mutations, whereas transcript fusions of HAMPs are relatively rare genomic events in common adult cancers. Collectively, 86.3% (63/73) of HAMPs have recurrent alterations in at least 1 cancer type and 16 HAMPs, including 9 understudied HAMPs, are identified as putative therapeutic targets across multiple cancer types. For example, the recurrent focal amplification of BRD9 is observed in 9 cancer types and genetic depletion of BRD9 inhibits tumor growth. Our systematic genomic analysis of HAMPs across a large-scale cancer specimen cohort may facilitate the identification and prioritization of potential drug targets and selection of suitable patients for precision treatment.


Assuntos
Genômica/métodos , Histonas/metabolismo , Mutação , Neoplasias/genética , Acetilação , Antineoplásicos/uso terapêutico , Variações do Número de Cópias de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histona Acetiltransferases/antagonistas & inibidores , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Microb Pathog ; 128: 236-244, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30611769

RESUMO

This work tested anti- Helicobacter pylori, free radicals scavenging and toxicity property as well as chemical constituents in the extract of chloroform (CE) and ethyl acetate (EAE) from the pedicel of Diospyros kaki L. (PDK-CE and PDK-EAE). There were 33 and 36 chemical constituents respectively in the extracts of PDK-CE and PDK-EAE, belonging to the fatty acids methyl ester, fatty acids, and stearic acids, as revealed by Gas Chromatography-Mass Spectrometry (GC-MS). The extracts did not exhibit any toxicity on NIH3T3 cells, but they significantly showed scavenging of NO, DPPH, and H2O2 free radicals. The extracts displayed in vitro anti-H. pylori activity. PDK-CE had the maximum inhibitory zone at a minimal inhibitory concentration (MIC) of 10 µg. ml-1 and the extract also triggered the cellular damage in the bacteria. PDK-CE extract had a high urease inhibitory activity (IC50 value of 8.5 µg). Further, in silico studies was performed by using 41 compounds against H. pylori urease (HPU) and H. pylori peptide deformylase (HPPD). The score value was the maximum (-19.58 kcal/mol) against HPU with 17-(5-ethyl-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol, while the score value was the maximum (-14.51 kcal/mol) against HPPD with hexadecanoic acid. The results demonstrated the importance of the pedicel extracts in future pharmaceutical drug development against H. pylori infections.


Assuntos
Amidoidrolases/efeitos dos fármacos , Antibacterianos/farmacologia , Biologia Computacional/métodos , Diospyros/química , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/farmacologia , Urease/efeitos dos fármacos , Animais , Antibacterianos/química , Compostos de Bifenilo/metabolismo , Morte Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Depuradores de Radicais Livres , Radicais Livres , Cromatografia Gasosa-Espectrometria de Massas/métodos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/enzimologia , Peróxido de Hidrogênio/metabolismo , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Células NIH 3T3/efeitos dos fármacos , Óxido Nítrico/metabolismo , Picratos/metabolismo , Extratos Vegetais/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA