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1.
Artigo em Inglês | MEDLINE | ID: mdl-31484223

RESUMO

Lys-N, also known as lysine-specific metalloendopeptidase, functions as the "sister" enzyme of lysyl endopeptidase (Lys-C) in proteomic research. Its digestion specificity at the N-terminal lysine residue makes it a very useful tool in proteomics analysis, especially in mass spectrometry-based de novo sequencing of proteins. Here we invented a complete production process of highly purified Lys-N from dry fruit of Grifola frondosa (Maitake Mushroom). The purification process includes 1 step of microfiltration plus 1 step of UF/DF (ultra-filtrated used in tandem with diafiltrated method) recovery step and 4 steps of chromatography purification. The overall yield of the process was approximately 6.7 mg Lys-N protein/kg dry fruit of Grifola frondosa. The assay data demonstrated that the purified Lys-N exhibited high enzymatic activity and specificity. The novel production process provides the first time to extract of Lys-N from dry fruit of Grifola frondosa. The process is also stable, scalable, and provides an economic way of producing the enzyme in large quantities for mass spectrum-based proteomics and other biological studies.

2.
Cancer Med ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31482686

RESUMO

Squamous cell carcinoma (SCC) is a unique clinical and histological category that accounts for about 30% of total lung cancer. To identify risk factors for lymph node metastasis and analyze the molecular features of these metastases in lung SCC, a retrospective study was performed for 170 lung SCC patients who underwent surgical treatment. The overall survival of these patients with or without lymph node metastasis (LM/NLM) was analyzed using the Kaplan-Meier method. We also used the TCGA database to compare the differentially expressed genes (DEGs) in patients with stage T1-2 and T3-4 lung SCC. Data from both our retrospective study and the TCGA database demonstrated a correlation between age and stage T1-T2 LM (P = .002). There were significant differences between the LM and NLM groups in both mean survival time and median survival time for different T-stages (P = .031). There were 176 upregulated and 177 downregulated DEGs between the LM and NLM groups in the stage T1-2 group and 93 upregulated and 34 downregulated DEGs in the stage T3-T4 group. These differentially expressed genes were predicted to participate in five cellular components, five molecular functions, and five biological processes. There were 20 genes, including GCG, CASR, NPY, CGA, TAC1, ALB, APOA1, CRH, CHRH, TRH, and GHSR, located at the core of the protein-protein interaction network in the stage T1-2 group and 11 genes, including F2, CASR, GRM1, GNRHR, GRPR, NTSR1, PROKR2, UTS2D, PTH, ALB, and FGA, in the stage T3-4 group. Overall, LM plays a key role in the treatment response and prognosis of SCC patients. Several risk factors, including age and stage, were identified for LM. There was a previously undiscovered enrichment of significant novel genes in lung SCC between the LM and NLM groups, which may have the potential for predicting prognosis and targeting.

3.
Sensors (Basel) ; 19(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487858

RESUMO

This paper presents a soft engine which performs up-and-down motion with four planar film-structured ionic polymer-metal composites (IPMC) actuators. This soft engine assembled with a stretchable Fresnel zone plate is capable of tuning the focus of ultrasonic beam. Instead of conventional clamps, we employ 3D printed frame pairs with magnets and a conductive gold cloth to provide an alternative solution for securing the IPMC actuators during assembly. The design and analysis of the zone plate are carefully performed. The zone plate allows the plane ultrasonic wave to be effectively focused. The motion of IPMC actuators stretch the metal-foil-made zone plate to tune the focal range of the ultrasonic beam. The zone plate, 3D frames and IPMC actuators were fabricated, assembled and tested. The stiffness normal to the stretchable zone plate with varied designs was investigated and the seven-zone design was selected for our experimental study. The force responsible for clamping the IPMC actuators, controlled by the magnetic attraction between the fabricated frames, was also examined. The driving voltage, current and resulting displacement of IPMC actuation were characterized. The developed soft engine stretching the zone plate to tune the focal point of the ultrasonic beam up to 10% was successfully demonstrated.

4.
PLoS One ; 14(8): e0219750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31369566

RESUMO

BACKGROUND: The cocirculation of duck hepatitis A virus subtypes 1 (DHAV-1) and 3 (DHAV-3) in ducklings has resulted in significant economic losses. Ducklings with DHAV-1 or DHAV-3 infection show similar clinical signs and gross lesions; hence, it is important to identify the viral subtypes in infected ducklings as early as possible for better clinical management. METHODS AND RESULTS: Based on multiple 5' noncoding region (5'-NCR) sequences of DHAV-1 and DHAV-3 strain alignments, universal and type-specific primers were designed and synthesized. With three primers in one-tube reverse transcription-PCR (RT-PCR), reference DHAV-1 and DHAV-3 isolates ranging over 60 years and across many different countries were successfully amplified, indicating that the primer sequences were completely conserved. The sequence results and the sizes of amplicons from reference DHAV-1 and DHAV-3 isolates are completely correlated with their subtypes. Moreover, with this one-tube RT-PCR system, amplicon sizes from liver samples of reference DHAV-1- or DHAV-3-infected birds fit closely with their subtypes, which was determined by virus isolation and neutralization testing. No other duck-origin RNA viruses were detected. The sensitivity of viral RNA detection was 10 pg. With this system, 20% subtype 1, 45% subtype 3, and 9% coinfection of two subtypes were detected in 55 clinical samples. CONCLUSIONS AND SIGNIFICANCE: This novel approach could be used for rapidly typing DHAV-1 or DHAV-3 infection in routine clinical surveillance or epidemiological screening.

5.
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.

6.
Mol Ther Nucleic Acids ; 17: 840-851, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31465963

RESUMO

Although accumulating evidence has demonstrated the key roles of enhancers in gene expression regulation, the contribution of genome-wide enhancer-enhancer interactions to developmental decisions remains unclear. Here we explored the cooperative regulation patterns among enhancers to understand their regulatory mechanism. We first filtered robust enhancers in embryonic stem cells (ESCs) through integrating bidirectional transcription, genomic location, and epigenetic modification. Genome-wide enhancer-enhancer interactions were then identified based on enhancer-promoter relationships that were derived from Hi-C data. We further explored the interacting principles of the identified enhancer-enhancer interactions. The results revealed that the observed cooperativity occurred mainly between enhancers distributed within a 1-kb to 10-Mb distance across the genome. In addition, enhancer-enhancer pairs had higher expression correlations than non-interacting pairs. Finally, we identified robust enhancers during human cardiac commitment, and we found that enhancers exhibited strong stage-specific expression patterns. We further inferred the enhancer-enhancer interactions based on RNA sequencing (RNA-seq) data in heart development, according to the regulatory principles characterized from Hi-C data. The identified enhancer-enhancer interaction networks (EEINs) presented highly dynamic linkages. Moreover, enhancers cooperatively targeted many marker genes in each developmental stage to regulate stage-specific functions, which contribute to the organization of cell identity in heart development. Our work will increase the understanding of enhancer regulation in human heart development.

7.
Microb Drug Resist ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369339

RESUMO

Aims: Antimicrobial resistance (AMR) has become a serious global health issue, which is exacerbated globally by the overuse and misuse of antimicrobial drugs. Improving awareness and understanding AMR through effective communication, education, and training is recommended by the World Health Organization as one of five key strategies of tackling AMR. This study explores the knowledge and perception of AMR, its educational status, and any potential associations among Chinese medical students. Results: A total of 2,616 students from four medical schools across China were enrolled in this study. Data reveal a general lack of knowledge about both antibiotic use and AMR that is related to school type, major, and clinical experience. Students' AMR knowledge was associated with their perception of issues in this area as well as their educational status. Results of a linear regression model show that learning about AMR in class (OR: 1.85, 95% CI: 1.47-2.23) and the hours spent learning about these issues (OR: 0.11, 95% CI: 0.07-0.15) were both positively associated with enhanced knowledge. Conclusions: A significant lack of knowledge about AMR is found among Chinese medical students, associated with their perception of these issues. The status of AMR education in medical schools nationally is therefore less than satisfactory and positively correlated with general knowledge of this issue.

8.
Bioresour Technol ; 291: 121853, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377510

RESUMO

The concentration of antibiotics in anaerobically digested swine wastewater (ADSW) usually gradually increases due to the addition of antibiotics in livestock feed. Lemna aequinoctialis was used to treatment synthetic ADSW contaminated by oxytetracycline (OTC) whose concentrations were 0.05, 0.25, 0.50 and 1.00 mg/L, and its influences on NH3-N and TP remove were investigated. The fresh weight, photosynthetic pigment and protein content of duckweed were also investigated. Results have shown that nutrient removal and duckweed growth followed the "dose-response" relationships, and 0.05 mg/L OTC could significantly promote the synthesis of photosynthetic pigments and proteins in duckweed. Meanwhile, the protein content gradually decreased during investigation. More important, the degradation products and possible degradation pathways of OTC were diagrammatized via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), and twelve intermediates were detected in the duckweed systems. This study can offer a novel view for phytoremediation of ADSW containing antibiotics by aquatic plants.


Assuntos
Antibacterianos/metabolismo , Araceae/metabolismo , Nutrientes , Oxitetraciclina/metabolismo , Águas Residuárias/química , Anaerobiose , Animais , Biodegradação Ambiental , Cromatografia Líquida , Suínos , Espectrometria de Massas em Tandem
9.
Turk J Gastroenterol ; 30(8): 722-731, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31418417

RESUMO

BACKGROUND/AIMS: We have previously identified a tight junction protein claudin-9 (CLDN9) as an upregulated gene in hepatocellular carcinoma (HCC) through an immunohistochemistry analysis. Here, we explore its function and clinical relevance in human HCC. MATERIALS AND METHODS: Stable transfection of the hepatocyte line HL7702 with CLDN9 was confirmed by the real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence. The impact of CLDN9 on the cell invasion and migration was assessed in vitro by a transwell assay and wound-healing experiment. Western blotting was used to determine the activation state of the Tyk2 (tyrosine kinase 2)/Stat3 (signal transducer and activator of transcription 3) pathway. Moreover, we used a Tyk2-RNAi assay to silence the expression of Tyk2 in CLDN9 expressing hepatocytes; subsequently, the impact of the Tyk2/Stat3 signaling pathway on the cell invasion and migration in vitro was assessed by a transwell assay and a wound-healing experiment. Furthermore, an immunohistochemistry method was utilized to explore the expression levels of CLDN9 and p-Stat3 in the HCC tissues and histologically non-neoplastic hepatic tissues. RESULTS: We confirmed that the expression of CLDN9 significantly enhanced the metastatic ability of hepatocytes in vitro, and the activation of the Stat3 pathway by Tyk2 was an important mechanism by which CLDN9 promoted hepatocyte aggressiveness in HCC. CONCLUSION: As an HCC proto-oncogene, CLDN9 affected the Stat3 signaling pathway via Tyk2 and ultimately enhanced the metastatic ability of hepatocytes.

10.
Molecules ; 24(17)2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31450679

RESUMO

The purpose of the present study is to examine the effects of melatonin on apoptosis and oxidative stress in mouse Leydig cells and to elucidate the mechanisms responsible for these effects. Our results indicated that 10 ng/mL of melatonin significantly promoted cell viability, the ratio of EdU-positive (5-Ethynyl-2'-deoxyuridine) cells, and increased the mRNA expression of proliferating cell nuclear antigen (PCNA), cyclin D1(CCND1), and cell division control protein 42 (CDC42) (p < 0.05). We also observed that melatonin inhibited apoptosis of mouse Leydig cells, accompanied with increased B-cell lymphoma-2 (BCL-2) and decreased BCL2 associated X (BAX) mRNA and protein expression. Moreover, addition of melatonin significantly decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, while it increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels (p < 0.05). In addition, we also found that melatonin increased the expression of SIRT1 (Silent information regulator 1) (p < 0.05). To explore the role of SIRT1 signaling in melatonin-induced cells, mouse Leydig cells were pretreated with EX527, an inhibitor of SIRT1. The protective effects of melatonin on mouse Leydig cells were reversed by EX527, as shown by decreased cell proliferation and increased cell apoptosis and oxidative stress. In summary, our results demonstrated that melatonin inhibited apoptosis and oxidative stress of mouse Leydig cells through a SIRT1-dependent mechanism.

11.
Inorg Chem ; 58(15): 9974-9981, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31317742

RESUMO

Metal oxide semiconductor (MOS) gas sensors operated at room temperature (RT) hold great promise for environmental monitoring in the emerging smart society. An in-depth understanding of the gas/MOS interfacial charge exchange under the ambient moist atmosphere is essential for subsequent molecule recognition. Herein, delafossite p-CuScO2 with a unique oxygen intercalation property was utilized. Eight orders of resistance tuning could be rationally achieved via controlling oxygen intercalation realized by air annealing (without altering the size and morphological properties), which allows extraction of both the intrinsic (gas/MOS interaction, p-type response) and extrinsic (gas/H2O/MOS interaction, pseudo-n-type response) sensing mechanisms upon exposure to ammonia molecules. This work could provide an insight into the underlying sensing mechanism of RT sensors working in an ambient moist atmosphere, and the unique n- to p-type switching contains rich molecule related features that could be potentially explored for molecule recognition.

12.
Life Sci ; 231: 116527, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176783

RESUMO

AIMS: Extracellular vesicles (EVs) are vital for information exchange between donor and recipient cells. When cells are stressed (e.g., by oxygen glucose deprivation, OGD), the complex information carried by the EVs is altered by the donor cells. Here, we aimed to analyze the proteomic differences between EVs derived from OGD-damaged cells and EVs derived from undamaged cells to explore the potential mechanisms by which EVs aggravate ischemic stroke (IS). MAIN METHODS: EVs released by rat adrenal gland PC12 cells subjected to 0, 3, 6, or 12 h of OGD were isolated. The proteins from the EVs secreted by each of the OGD groups were profiled using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). We predicted the functions, pathways, and interactions of the differentially expressed proteins using Gene Ontology (GO), KEGG pathways, and STRING. We used parallel reaction monitoring (PRM) to validate our results. KEY FINDINGS: We identified several differentially expressed proteins in the OGD groups as compared to the controls: 170 proteins in the 3 h OGD EVs, 44 proteins in the 6 h OGD EVs, and 77 proteins in the 12 h OGD EVs (fold-change ≥1.5; p ≤ 0.05). These proteins were associated with oxidative stress, carbohydrate metabolism, protein synthesis and degradation, and thrombosis. SIGNIFICANCE: We identified changes in protein expression in the EVs secreted by OGD-damaged cells, highlighting potential mechanisms by which EVs aggravate IS. Our results also suggested potential protein targets, which may be useful for the prevention and treatment of IS.

13.
Int J Syst Evol Microbiol ; 69(8): 2486-2491, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169487

RESUMO

The taxonomic position of an actinobacterium isolated from a desert soil sample collected from Badain Jaran Desert, designated as CPCC 204711T, was established using a polyphasic approach. Cells of the isolate were Gram-staining-positive, aerobic, non-motile cocci. Good growth was observed at 28 °C (range 20-40 °C), pH 7.0 (range pH 6.0-8.0) and 0-1 % NaCl concentration (range 0-5 %, w/v). Galactose, arabinose and ribose were detected as the sugar compositions in the whole cell hydrolysates. The peptidoglycan type was A3gamma (ll-Dpm-Gly). MK-9(H4) was detected as the predominant menaquinone, and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, several unidentified glycolipids, and one unidentified amino-glycolipid were detected as the major polar lipids. The predominant fatty acid was anteiso-C15 : 0. The genomic DNA G+C content was 73.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204711T affiliated to the family Propionibacteriaceae, in which the strain formed a distinct phylogenetic lineage next to the genus Mariniluteicoccus, with the highest 16S rRNA gene sequence similarity of 96.0 % to Mariniluteicoccus endophyticus YIM 2617T. Both phylogenetic analysis and phenotypic characteristics supported that strain CPCC 204711T represents a novel species of a new genus in the family Propionibacteriaceae, for which the name Desertihabitans aurantiacus gen. nov., sp. nov. is proposed, with CPCC 204711T (=KCTC 39977T=DSM 105431T) as the type strain.


Assuntos
Clima Desértico , Filogenia , Propionibacteriaceae/classificação , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Peptidoglicano/química , Fosfolipídeos/química , Propionibacteriaceae/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
14.
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.

15.
Zhongguo Fei Ai Za Zhi ; 22(5): 255-263, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31109434

RESUMO

BACKGROUND: Lung cancer is one of the common malignant tumors that impair human health. With the development of epigenetics, the researchers found that enhancer of Zeste homolog 2 (EZH2) is highly expressed in lung cancer tissue and its expression is closely related to the prognosis. EZH2 inhibitor can also enhance the sensitivity of tumor cells to a variety of anti-tumor drugs. The purpose of this study is to investigate the effect of combination of EZH2 inhibitor and gefitinib on the proliferation, apoptosis and migration of Gefitinib-resistant lung cancer cells. METHODS: PC9 and PC9/AB2 cells were used for this study. CCK-8 and EdU experiment were used to detect combined treatment on cell viability and proliferation activity; Wound healing assay and Transwell chamber experiment were used to determine the effects of combination therapy on cell migration ability; Flow cytometry was used to detect the effect of combination therapy on EZH2 and apoptosis; Western blot was used to observe the effect of combination therapy on epidermal growth factor receptor (EGFR) signaling pathway-related proteins expression. RESULTS: In gefitinib-resistant cell line PC9/AB2, gefitinib combined with EZH2 inhibitor GSK343 can significantly inhibit cell viability, reduce cell migration and increase cell apoptosis. At the same time, combination therapy can significantly inhibit the expression of EZH2 and phosphorylation EGFR proteins. CONCLUSIONS: The combination of EZH2 inhibitor GSK343 and gefitinib sensitize PC9/AB2 cell to gefitinib response. This study also suggests that synergistic therapy plays a role in the reversal of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) resistance in lung cancer.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Receptores ErbB/antagonistas & inibidores , Gefitinibe/farmacologia , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos
16.
Zhongguo Fei Ai Za Zhi ; 22(5): 264-270, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31109435

RESUMO

BACKGROUND: Lung cancer is one of the most deadly cancers in the world for human. In recent years, the effect of targeted therapy has become increasingly significant. Apatinib is a multi-target anti-tumor drug that is currently under study. The purpose of this study is to investigate the effects of Apatinib on the biological characteristics of lung cancer cells and its possible mechanism. METHODS: Lung cancer cell lines H1299 and H3255 were cultured in vitro. The effects of Apatinib on proliferation, migration and invasion of H1299 and H3255 cells were detected by cell proliferation assays wound healing assays and Transwell assays. The protein expression related to cancer angiogenesis and invasion was detected by Western blot. RESULTS: Apatinib significantly inhibited the proliferation, migration and invasion of H1299 and H3255 in a concentration-dependent manner. Western blot showed that with the increasing of drug concentration, VEGF, VEGFR2, N-cadherin, MMP9, MMP2 and Vimentin were down-regulated, and E-cadherin were up-regulated. CONCLUSIONS: Apatinib can inhibit the invasion and migration of lung adenocarcinoma cells H1299 and H3255. By regulation of epithelial-mesenchymal transition and the expression of matrix metalloproteinase-related proteins.


Assuntos
Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Piridinas/farmacologia , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica
17.
Zhongguo Fei Ai Za Zhi ; 22(5): 280-288, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31109437

RESUMO

BACKGROUND: Lung cancer is a malignant tumor disease with high morbidity and high mortality. The non-small cell lung cancer (NSCLC) is the most common type, among them, lung squamous cell carcinoma own special pathological type and specific treatment, is a subtype of non-small cell lung cancer and can be divided into peripheral type and central type according to clinical phenotype. This study explores the differences in gene levels and their potential values based on clinical differences between central and peripheral in lung squamous cell carcinoma. METHODS: The lung squamous cell carcinoma dataset was collected from The Cancer Genome Atlas (TCGA) database, clinical information and the corresponding gene expression profiles were downloaded. Then we further sort and analyze all these data. RESULTS: In clinical characteristics analysis, result showed that central lung squamous cell carcinoma was more likely to metastasis with lymph node than peripheral lung squamous cell carcinoma (46.2%, 67/145 vs 28.9%, 26/90; P=0.019), while there were no significant differences in gender, age, tumor size, distant metastasis, tumor node metastasis (TNM) stage, and EGFR mutation. Gene expression analysis showed 1,031 differentially expressed genes between central and peripheral lung squamous cell carcinoma, of which 629 genes were up-regulated and 402 genes were down-regulated (peripheral vs central). Further enrichment analysis showed differentially expressed genes were mainly riched in 6 signaling pathways. Among them, the neuroactive ligand-receptor interaction pathway was the main enrichment pathway of differentially expressed genes, and other differential expressed genes were mainly involved in lipid metabolism and glucose metabolism. The analysis of interaction network showed that hepatocyte nuclear factor 1 homeobox A (HNF1A) and cytochrome p450 family, Cytochrome P450 3A4 (CYP3A4) own widely effect in up-regulated genes, while ALB and APOA1 at the key positions of the network in down-regulated genes were CONCLUSIONS: Central and peripheral lung squamous cell carcinoma showed clinical phenotype difference not only reflected in the incidence of lymph node metastasis, but also in gene expression profiles. Among them, HNF1A, CYP3A4, ALB, APOA1 at the key position of the differential gene interaction network and maybe as regulatory factors in the phenotypic difference.


Assuntos
Carcinoma de Células Escamosas/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Idoso , Feminino , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fumar/genética
18.
J Nat Prod ; 82(5): 1149-1154, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31070914

RESUMO

Isarubrolones are bioactive polycyclic tropoloalkaloids from Streptomyces. Three new isarubrolones (2-4), together with the known isarubrolone C (1) and isatropolones A (5) and C (6, 3( R)-hydroxyisatropolone A), were identified from Streptomyces sp. CPCC 204095. The structures of these compounds were determined using a combination of mass spectrometry, 1D and 2D NMR spectroscopy, and ECD. Compounds 3 and 4 feature a pyridooxazinium unit, which is rarely seen in natural products. Compound 6 could conjugate with amino acids or amines to expand the structural diversity of isarubrolones with a pentacyclic or hexacyclic core. Importantly, 1 and 3-6 were found to induce complete autophagy.

19.
Theriogenology ; 134: 1-10, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108431

RESUMO

The mammalian Sirtuin family of seven enzymes, members of the NAD+-dependent histone deacetylase family that modify histones via direct deacetylation, is involved in the regulation of many antioxidant and oxidative stresses. In the present study, we explored the effects of nicotinamide (NAM)-induced oxidative stress on the in vitro development of bovine embryos, on the acetylation of histone H3 lysine 56 (H3K56ac) and on expression of apoptosis-related genes. Treatment with NAM (10, 20 or 40 mM for 24, 48 or 196 h) during IVC resulted in significantly decreased blastocyst formation (24 h: 38.8 vs. 33.1, 27.3 and 10.2%, with P > 0.05, P < 0.05 and P < 0.01, respectively; 48 h: 37.5 vs. 28.2, 13.4 and 0%, with P < 0.05 and P < 0.01, respectively; 196 h: 35.8 vs. 23.4, 0 and 0%, with P < 0.05, respectively). Treatment with NAM (20 and 40 mM for 24 h) resulted in increased intracellular reactive oxygen species (ROS) levels in 2-cell and blastocysts, and apoptotic cell numbers in blastocysts and decreased mitochondrial membrane potential (ΔΨ) in 2-cell embryos (P < 0.05). Polydatin (PD) and I-CBP112 rescued the 20 mM NAM-induced embryo developmental defects and reduced ROS levels and apoptotic cell numbers in blastocysts (P < 0.05). The gene expression of NF-κB, COX2 and p53 was significantly increased in the NAM-treated group. Immunofluorescence analysis confirmed that the protein levels of nuclear factor-kappa B (NF-κB) decreased significantly after PD and I-CBP112 treatment compared with the control (P < 0.05). High level of H3K56ac induced by NAM was decreased after PD and I-CBP112 treatment (P < 0.05). These findings suggest that NAM treatment induces high levels of H3K56 acetylation that may be involved in oxidative stress-induced bovine developmental defects, which can be tolerated by PD and I-CBP112 treatment.

20.
Neurochem Res ; 44(8): 1807-1817, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093905

RESUMO

Cerebral ischemic injury is a leading cause of human mortality and disability, seriously threatening human health in the world. Activin A (Act A), as a well-known neuroprotective factor, could alleviate ischemic brain injury mainly through Act A/Smads signaling. In our previous study, a noncanonical Act A/Smads signal loop with self-amplifying property was found, which strengthened the neuroprotective effect of Act A. However, this neuroprotective effect was limited due to the self-limiting behavior mediated by Smad anchor for receptor activation (SARA) protein. It was reported that microRNA-17-5p (miR-17-5p) could suppress the expression of SARA in esophageal squamous cell carcinoma. Thus we proposed that knockdown of miR-17-5p could strengthen the neuroprotective effect of Act A/Smads signal loop through SARA. To testify this hypothesis, oxygen-glucose deficiency (OGD) was introduced to highly differentiated rattus pheochromocytoma (PC12) cells. After the transfection of miR-17-5p mimic or inhibitor, the activity of Act A signal loop was quantified by the expression of phosphorylated Smad3. The results showed that suppression of miR-17-5p up-regulated the expression of SARA protein, which prolonged and strengthened the activity of Act A signaling through increased phosphorylation of downstream Smad3 and accumulation of Act A ligand. Further luciferase assay confirmed that SARA was a direct target gene of miR-17-5p. These practical discoveries will bring new insight on the endogenous neuroprotective effects of Act A signal loop by interfering a novel target: miR-17-5p.

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