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1.
Clin Infect Dis ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173725

RESUMO

BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. RESULTS: Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. CONCLUSION: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.

2.
Mil Med Res ; 7(1): 4, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029004

RESUMO

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Infecção Hospitalar , Controle de Infecções , Programas de Rastreamento , Equipamento de Proteção Individual , Pneumonia Viral , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Diagnóstico Diferencial , Medicamentos de Ervas Chinesas , Medicina Baseada em Evidências , Hidratação , Humanos , Controle de Infecções/normas , Pulmão/diagnóstico por imagem , Epidemiologia Molecular , Cuidados de Enfermagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
3.
Pathology ; 52(2): 206-212, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31883669

RESUMO

Ovarian lymphoma, whether a primary or secondary condition, is very rare. Little is known about its genetic aberrations. Here, we reviewed the clinical, morphological and immunohistochemical characteristics of nine ovarian diffuse large B-cell lymphoma (DLBCL) cases and performed fluorescence in situ hybridisation (FISH) analysis to detect MYC, BCL2 and BCL6 translocations. We also performed whole exome sequencing analysis to determine their genomic features compared with those of conventional extranodal DLBCL. The results showed that six of nine cases were bilateral and three cases were left-sided. Histologically, the tumour cells were homogeneous and a starry-sky pattern was very common in ovarian DLBCL (Burkitt-like). Immunohistochemically, most of the cases (7/9) were germinal centre B-cell-like (GCB) subtype, and dual expression of MYC and BCL2 was found in three cases of ovarian DLBCL. A double-hit (involving MYC and BCL6) phenotype was found in one case of ovarian DLBCL (GCB subtype). Sequencing analysis revealed that NOTCH4, NCOR2, BCL10 and CARD11 were frequently mutated both in ovarian DLBCL and conventional extranodal DLBCL. COL27A1, PRKCB, HLA-A, NOTCH3 and HDAC4 mutations were found only in ovarian DLBCL but not in conventional DLBCL, and NOTCH3 and HDAC4 mutations were only identified in the GCB subtype. Furthermore, several signalling pathways including the B-cell receptor, Epstein-Barr virus infection, HTLV-1 infection, Notch, PI3K-AKT and mTOR were found to be involved in ovarian DLBCL. Our results broaden the understanding of the clinicopathological and molecular characteristics of ovarian DLBCL and compare their genetic features to those of conventional extranodal DLBCL for the first time.

4.
Int J Biol Macromol ; 141: 351-357, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31442507

RESUMO

Escherichia coli, one of the most well-studied gram-negative bacterial species, encodes two ubiquitin-like proteins (UBLs), ThiS and MoaD. The studies on prokaryotic UBLs such as Pup, and small archaeal modifier protein have revealed the function of UBLs. However, in gram-negative bacteria, the functions of UBLs in protein modification are still poorly understood to date. Here, we report that ThiS, which has a ß-grasp fold and carboxy-terminal diglycine motif similar to ubiquitin, is able to form protein conjugates in vivo and in vitro. We also constructed in vitro ThiS conjugation (thisylation) system and identified the modified lysine sites by MS/MS, this provides an essential platform for studying the UBLs thisylation system in E. coli. The modification system is dependent on lysine 83 (ATPase activity site) and cysteine 169 (zinc binding site) in ThiF and three important substrates, GroEL, PriC, FtsA, were found to be covalently modified by this system in vitro. Taken together, this study provided evidence that the protein conjugation function of ß-grasp fold UBLs is conserved in the three major evolutionary lineages of life.

5.
ACS Omega ; 4(6): 10620-10628, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31460160

RESUMO

The synthetic water-soluble polymer, partially hydrolyzed polyacrylamide (HPAM), has been most widely used for enhanced oil recovery (EOR); however, its poor thermal stability and weak salt tolerance impede further application in high-temperature and high-salinity oil reservoirs. To address such deficiencies, three polysaccharides, xanthan gum, diutan gum, and scleroglucan, were examined in comparison with HPAM on rheological behaviors, shearing resistance, long-term thermal stability, and core flooding test. It was found that all of these three polysaccharides were less sensitive to salinity and shearing time, while HPAM showed a monotonous decrease in viscosity with increasing monovalent cations and shearing history. After 90 days of aging at 85 °C and 10.1 × 104 mg·L-1 of total dissolved solids with 1.0 × 103 mg·L-1 of Ca2+, the viscosity of diutan gum and scleroglucan solutions nearly remained unchanged; on the contrary, the viscosity of xanthan gum and HPAM solutions drops massively. Core flooding tests at 85 °C with the same initial viscosity demonstrated that all polymers showed good transportation in porous media, and 16, 13, and 11% of oil recovery were obtained by diutan gum, scleroglucan, and xanthan gum, respectively, while only 10% was obtained from HPAM. These comparative results may underpin the potential of diutan gum and scleroglucan to be used in the EOR process in HTHS oil reservoirs.

6.
3 Biotech ; 9(8): 296, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31321200

RESUMO

The prolactin receptor (PRLR), a type I cytokine receptor, must bind prolactin (PRL) to act on target cells to mediate various physiological functions, including reproduction and lactation. This study identified an 80-bp insertion/deletion (indel) polymorphism in the 3'-untranslated region (3'-UTR) of the chicken PRLR gene in 3736 individuals from 15 breeds and analyzed its associations with growth and carcass traits in an F2 resource population. The results of the association analysis indicated that the 80-bp indel polymorphism was significantly (P < 0.05) or very significantly (P < 0.01) associated with multiple growth and carcass traits, such as body weight, leg weight, and shank length. In addition, we found that during the breeding process of commercial laying hens and commercial broilers, the 80-bp indel locus was artificially selected for the II genotype. Together, our findings reveal that this 80-bp indel polymorphism has potential as a new molecular marker for marker-assisted selection of chicken growth and carcass traits.

7.
Nat Immunol ; 20(7): 835-851, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31160797

RESUMO

How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.


Assuntos
Apresentação do Antígeno/imunologia , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/imunologia , Oncogenes , RNA Longo não Codificante/genética , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Adenoma/genética , Adenoma/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
8.
J Gastroenterol Hepatol ; 34(10): 1869-1877, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31038805

RESUMO

BACKGROUND AND AIM: DNA hypermethylation has emerged as a novel molecular biomarker for the diagnosis and prognosis prediction of many cancers. We aimed to identify clinically useful biomarkers regulated by DNA methylation in hepatocellular carcinoma (HCC). METHODS: Genome-wide methylation analysis in HCCs and paired noncancerous tissues was performed using an Illumina Infinium HumanMethylation 450K BeadChip array. Methylation-specific polymerase chain reaction and pyrosequencing were used to validate the methylation status of selected genes in 100 paired HCCs and noncancerous samples. RESULTS: A total of 97 027 (20.0%) out of 485 577 CpG sites significantly were differed between HCC and noncancerous tissues. Among all the significant CpG sites, 48.8% are hypermethylated and 51.2% are hypomethylated in HCCs. Multiple signaling pathways (AMP-activated protein kinase, estrogen, and adipocytokine) involved in gene methylation were identified in HCC. FES was selected for further analysis based on its high level of methylation confirmed by polymerase chain reaction and pyrosequencing. The result showed that FES hypermethylation was correlated with tumor size (0.001), serum alpha fetoprotein (0.023), and tumor differentiation (0.006). FES protein was significantly downregulated in 51/100 (51%) HCCs, and 94.12% (48/51) of them were due to promoter hypermethylation. Both FES hypermethylation and protein downregulation were associated with the progression-free survival and overall survival of HCC patients. Overexpressed and knockdown of FES confirmed its inhibitory effect on the proliferation and migration of HCC cells. CONCLUSIONS: We identified many new differentially methylated CpGs in HCCs and demonstrate that FES functions as a tumor suppressor gene in HCC and its methylation status could be used as an indicator for prognosis of HCC.

9.
Cancer ; 125(14): 2409-2422, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31012964

RESUMO

BACKGROUND: Over 96% of high-grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer. METHODS: A novel strategy is presented for circumventing alterations in p53 by inducing the tumor-suppressor isoform TAp63 (transactivation domain of tumor protein p63) through its direct downstream target, microRNA-130b (miR-130b), which is epigenetically silenced and/or downregulated in chemoresistant ovarian cancer. RESULTS: Treatment with miR-130b resulted in: 1) decreased migration/invasion in HEYA8 cells (p53 wild-type) and disruption of multicellular spheroids in OVCAR8 cells (p53-mutant) in vitro, 2) sensitization of HEYA8 and OVCAR8 cells to cisplatin (CDDP) in vitro and in vivo, and 3) transcriptional activation of TAp63 and the B-cell lymphoma (Bcl)-inhibitor B-cell lymphoma 2-like protein 11 (BIM). Overexpression of TAp63 was sufficient to decrease cell viability, suggesting that it is a critical downstream effector of miR-130b. In vivo, combined miR-130b plus CDDP exhibited greater therapeutic efficacy than miR-130b or CDDP alone. Mice that carried OVCAR8 xenograft tumors and were injected with miR-130b in 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) liposomes had a significant decrease in tumor burden at rates similar to those observed in CDDP-treated mice, and 20% of DOPC-miR-130b plus CDDP-treated mice were living tumor free. Systemic injections of scL-miR-130b plus CDDP in a clinically tested, tumor-targeted nanocomplex (scL) improved survival in 60% and complete remissions in 40% of mice that carried HEYA8 xenografts. CONCLUSIONS: The miR-130b/TAp63 axis is proposed as a new druggable pathway that has the potential to uncover broad-spectrum therapeutic options for the majority of p53-altered cancers.

10.
Med Sci Monit ; 25: 2112-2121, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30898992

RESUMO

BACKGROUND Our research was designed to investigate the relationship of spleen tyrosine kinase (Syk) and inflammatory factors with coronary heart disease (CHD) and the risk factors of CHD. MATERIAL AND METHODS In our study, 226 patients were enrolled, from October 2017 to March 2018. Clinical and biochemical data were collected. We collected samples of peripheral blood monocytes (PBMs) from the enrolled patients. The patients were divided in 4 groups: patients without coronary artery disease (control group), patients with stable angina pectoris (SAP group), patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS group), and patients with ST-segment elevation acute myocardial infarction group (STEMI group). We detect the protein levels of Syk and inflammatory factors expression by western blot. RESULTS Our results found the protein levels of Syk and inflammatory factors expression in the NSTE-ACS and STEMI groups were higher than those in the SAP and control groups. The protein levels of Syk and inflammatory factors expression in the SAP group were higher than those in the control group. Moreover, there were many risk factors significantly associated with Syk. Besides that, these risk factors were also independent risk factors of CHD. CONCLUSIONS Our results found that the level of Syk was associated with the severity of CHD. From our study, we found that higher levels of Syk and inflammatory factors protein were associated with worse results of the CHD. For the first time, Syk was reported to be a promising therapeutic factor for CHD patients.


Assuntos
Quinase Syk/biossíntese , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/sangue , Inflamação/enzimologia , Masculino , Pessoa de Meia-Idade , Monócitos/enzimologia , Intervenção Coronária Percutânea/métodos , Fatores de Risco , Quinase Syk/sangue , Transcriptoma
11.
J Clin Invest ; 129(3): 1129-1151, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30741721

RESUMO

Epithelial-mesenchymal transition (EMT) contributes significantly to interstitial matrix deposition in diabetic kidney disease (DKD). However, detection of EMT in kidney tissue is impracticable, and anti-EMT therapies have long been hindered. We reported that phosphatase and tensin homolog (PTEN) promoted transforming growth factor beta 1 (TGF-ß), sonic hedgehog (SHH), connective tissue growth factor (CTGF), interleukin 6 (IL-6), and hyperglycemia-induced EMT when PTEN was modified by a MEX3C-catalyzed K27-linked polyubiquitination at lysine 80 (referred to as PTENK27-polyUb). Genetic inhibition of PTENK27-polyUb alleviated Col4a3 knockout-, folic acid-, and streptozotocin-induced (STZ-induced) kidney injury. Serum and urine PTENK27-polyUb concentrations were negatively correlated with glomerular filtration rate (GFR) for diabetic patients. Mechanistically, PTENK27-polyUb facilitated dephosphorylation and protein stabilization of TWIST, SNAI1, and YAP in renal epithelial cells, leading to enhanced EMT. We identified that a small molecule, triptolide, inhibited MEX3C-catalyzed PTENK27-polyUb and EMT of renal epithelial cells. Treatment with triptolide reduced TWIST, SNAI1, and YAP concurrently and improved kidney health in Col4a3 knockout-, folic acid-injured disease models and STZ-induced, BTBR ob/ob diabetic nephropathy models. Hence, we demonstrated the important role of PTENK27-polyUb in DKD and a promising therapeutic strategy that inhibited the progression of DKD.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal , Rim/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Autoantígenos/genética , Autoantígenos/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Humanos , Rim/patologia , Camundongos , Camundongos Knockout , PTEN Fosfo-Hidrolase/genética , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
12.
Cell Res ; 29(4): 286-304, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30631154

RESUMO

Despite the structural conservation of PTEN with dual-specificity phosphatases, there have been no reports regarding the regulatory mechanisms that underlie this potential dual-phosphatase activity. Here, we report that K27-linked polyubiquitination of PTEN at lysines 66 and 80 switches its phosphoinositide/protein tyrosine phosphatase activity to protein serine/threonine phosphatase activity. Mechanistically, high glucose, TGF-ß, CTGF, SHH, and IL-6 induce the expression of a long non-coding RNA, GAEA (Glucose Aroused for EMT Activation), which associates with an RNA-binding E3 ligase, MEX3C, and enhances its enzymatic activity, leading to the K27-linked polyubiquitination of PTEN. The MEX3C-catalyzed PTENK27-polyUb activates its protein serine/threonine phosphatase activity and inhibits its phosphatidylinositol/protein tyrosine phosphatase activity. With this altered enzymatic activity, PTENK27-polyUb dephosphorylates the phosphoserine/threonine residues of TWIST1, SNAI1, and YAP1, leading to accumulation of these master regulators of EMT. Animals with genetic inhibition of PTENK27-polyUb, by a single nucleotide mutation generated using CRISPR/Cas9 (PtenK80R/K80R), exhibit inhibition of EMT markers during mammary gland morphogenesis in pregnancy/lactation and during cutaneous wound healing processes. Our findings illustrate an unexpected paradigm in which the lncRNA-dependent switch in PTEN protein serine/threonine phosphatase activity is important for physiological homeostasis and disease development.

13.
Hum Pathol ; 84: 309-320, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30339972

RESUMO

Classical Hodgkin lymphoma (cHL) and ALK- anaplastic large cell lymphoma (ALCL) share many morphologic and immunohistochemical features, causing difficulties in differential diagnosis. Aberrant T-cell/B-cell antigen (TCA/BCA) expression in cHL/ALCL has previously been reported, but differences in the broader morphologic and genetic features still remain unclear. We first explored the histologic and immunohistochemical characteristics of cHL and ALCL with or without aberrant expression. Of 68 cHL cases, 10 (14.71%) were found to express 1 or more TCAs, and the frequency was as follows: CD4 > CD2 > CD3 > CD5 = CD7. Only 1 (3.33%) of 30 ALCL cases expressed BCA. Histologically, the main subtypes of cHL with aberrant TCA expression were LD and NS2. These aberrant TCA-expressing cHL tumor cells exhibited some ALCL features, and the aberrant BCA-expressing ALCL tumor cells displayed cHL characteristics. We also performed whole-exome sequencing analysis on cHL and ALCL samples with aberrant expression and compared them with those without aberrant expression. The results of this analysis showed that GNE and CACNB2 mutations, involved in the MAPK signaling pathway, may play an important role in cHL. In addition, 135 mutation sites involved in multiple signaling pathways were identified in ALCL. In the aberrant-expression cases, genetic features were similar between cHL and ALCL, consistent with their morphologic features. Our results broaden the understanding of the histologic and immunohistochemical characteristics of cHL and ALCL with aberrant expression and, for the first time, compare genetic features between cHL and ALCL with and without aberrant expression.


Assuntos
Antígenos de Diferenciação de Linfócitos B/biossíntese , Antígenos de Diferenciação de Linfócitos T/biossíntese , Biomarcadores Tumorais/imunologia , Doença de Hodgkin/imunologia , Linfoma Anaplásico de Células Grandes/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/genética , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
ACS Appl Mater Interfaces ; 10(37): 31515-31525, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30132326

RESUMO

In this work, we propose a novel concept to develop two fluorophores 2-(10 H-phenothiazin-10-yl)thianthrene 5,5,10,10-tetraoxide (PTZ-TTR) and 2-(4-(10 H-phenothiazin-10-yl)phenyl)thianthrene 5,5,10,10-tetraoxide (PTZ-Ph-TTR) showing dual conformations for highly efficient single-emitter white organic light-emitting diodes (WOLEDs). Both molecules exist in two stable conformations. Their nearly orthogonal forms own lower energy levels and show thermally activated delayed fluorescence (TADF) characteristics, whereas their nearly planar conformers possess higher energy levels and show only prompt fluorescence. These dual conformers were exploited for fabricating WOLEDs with complementary emission colors contributed by the two conformations. Moreover, the originally wasted triplet energy on the nearly planar conformation can be transferred to the nearly orthogonal one and then harvested via the TADF channel, realizing full exciton utilization. A PTZ-TTR-based single-emitter device exhibits standard white emission with a CIE coordinate of (0.33, 0.33) and a high color rendering index value of 92. On the other hand, the PTZ-Ph-TTR-based single-emitter device realizes an emission approaching warm white light and a high maximum external quantum efficiency of 16.34%. These results demonstrate an alternative approach for designing high-performance WOLEDs based on single TADF emitters.

15.
Cancer Res ; 78(16): 4524-4532, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29967256

RESUMO

Long noncoding RNA (lncRNA) is yet to be linked to cancer metabolism. Here, we report that upregulation of the lncRNA LINC00538 (YIYA) promotes glycolysis, cell proliferation, and tumor growth in breast cancer. YIYA is associated with the cytosolic cyclin-dependent kinase CDK6 and regulated CDK6-dependent phosphorylation of the fructose bisphosphatase PFK2 (PFKFB3) in a cell-cycle-independent manner. In breast cancer cells, these events promoted catalysis of glucose 6-phosphate to fructose-2,6-bisphosphate/fructose-1,6-bisphosphate. CRISPR/Cas9-mediated deletion of YIYA or CDK6 silencing impaired glycolysis and tumor growth in vivo In clinical specimens of breast cancer, YIYA was expressed in approximately 40% of cases where it correlated with CDK6 expression and unfavorable survival outcomes. Our results define a functional role for lncRNA in metabolic reprogramming in cancer, with potential clinical implications for its therapeutic targeting.Significance: These findings offer a first glimpse into how a long-coding RNA influences cancer metabolism to drive tumor growth. Cancer Res; 78(16); 4524-32. ©2018 AACR.


Assuntos
Neoplasias da Mama/genética , Proliferação de Células/genética , RNA Longo não Codificante/genética , Neoplasias da Mama/patologia , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Quinase 6 Dependente de Ciclina/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Glucose/metabolismo , Glicólise/genética , Humanos , Fosforilação
16.
Pharmacogn Mag ; 14(54): 214-219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29720834

RESUMO

Background: The rhizome of Atractylodes lancea (AL) is usually used for the treatment of various diseases such as spleen deficiency syndrome (SDS). Both bran-processed and crude AL is included in Chinese Pharmacopoeia. The different efficacies of bran-processed and crude AL on SDS are largely unknown, and the mechanisms of AL effects have not been fully elucidated. Objective: The objective of the study was to compare the effects of bran-processed and crude AL and then assess the mechanisms of treating SDS. Materials and Methods: The model of SDS in rats was established using excessive exertion, combined with an irregular diet and intragastric administration of the extract of Sennae Folium, and different doses of bran-processed and crude AL were gavaged. The serum was analyzed by an enzyme-linked immunosorbent assay (ELISA), and small intestinal tissues were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Results: The injury of SDS was alleviated by the treatment of bran-processed and crude AL. Compared to model group, the indexes of trypsin (TRY), amylase (AMS), vasoactive intestinal peptide (VIP), somatostatin (SS), gastrin (GAS), substance P (SP), Na+-K+-ATPase, and succinic dehydrogenase in serum of each administration group were increased by ELISA, and the mRNA expressions of VIP, SS, GAS, and SP in small intestinal tissues were increased by RT-PCR. Furthermore, in a dose-dependent manner, the bran-processed and crude AL increased the levels of TRY, AMS, VIP, and GAS and the mRNA expression levels of VIP. Compared with the crude AL, the bran-processed AL was more effective in treating SDS. Conclusion: Through the mechanisms of treating SDS by AL, both bran-processed and crude AL has alleviated the symptoms of SDS. SUMMARY: Both bran-processed and crude Atractylodes lancea (AL) alleviated symptoms of spleen deficiency syndrome (SDS)Comparing with crude AL, bran. processed AL was more effective in treating SDSThe efficacy of AL could be partly attributed to digestive enzyme activity, gastrointestinal hormone levels, membrane protein activity, and changes in mitochondrial activity. Abbreviations used: AL: Atractylodes lancea; TRY: Trypsin; AMS: Amylase; VIP: Vasoactive intestinal peptide; SS: Somatostatin; GAS: Gastrin; SP: Substance P; ELISA: The enzyme-linked immunosorbent assay; mRNA: Messenger ribonucleic acid; SDH: Succinic dehydrogenase; RT-PCR: Reverse transcription-polymerase chain reaction; TCM: Traditional Chinese medicine; SDS: Spleen deficiency syndrome.

17.
Int J Med Robot ; 14(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28660644

RESUMO

BACKGROUND: The performance of robotic end-effector movements can reflect the user's operation skill difference in robot-assisted minimally invasive surgery. This study quantified the trade-off of speed-accuracy-stability by kinematic analysis of robotic end-effector movements to assess the motion control skill of users with different levels of experience. METHODS: Using 'MicroHand S' system, 10 experts, 10 residents and 10 novices performed single-hand test and bimanual coordination test. Eight metrics based on the movements of robotic end-effectors were applied to evaluate the users' performance. RESULTS: In the single-hand test, experts outperformed other groups except for movement speed; in the bimanual coordination test, experts also performed better except for movement time and movement speed. No statistically significant difference in performance was found between residents and novices. CONCLUSIONS: The kinematic differences obtained from the movements of robotic end-effectors can be applied to assess the motion control skill of users with different skill levels.


Assuntos
Laparoscopia/instrumentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Fenômenos Biomecânicos , Competência Clínica , Desenho de Equipamento , Gastroenterologia/instrumentação , Ginecologia/instrumentação , Humanos , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Modelos Estatísticos , Movimento (Física) , Reprodutibilidade dos Testes , Procedimentos Cirúrgicos Robóticos/educação , Cirurgia Assistida por Computador , Urologia/instrumentação
18.
Curr Microbiol ; 75(4): 450-455, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29260303

RESUMO

In Escherichia coli, the DnaK/DnaJ chaperone can control the stability and activity of σ32, which is the key factor in heat shock response. Heterologous expression of eukaryotic molecular chaperones protects E. coli from heat stress. Here, we show that BAH1, an E3 ligase from plant that has a similar zinc finger domain to DnaJ, can perform block the effect of DnaK on σ32 in Escherichia coli. By constructing a chimeric DnaJ protein, with the J-domain of DnaJ fused to BAH1, we found BAH1 could partially compensate for the DnaJ' zinc finger domain in vivo, and that it was dependent on the zinc finger domain of BAH1. Furthermore, BAH1 could interact with both σ32 and DnaK to increase the level of HSPs, such as GroEL, DnaK, and σ32. These results suggested that the zinc finger domain was conserved during evolution.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Fator sigma/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/química , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Chaperonas Moleculares/genética , Ligação Proteica , Domínios Proteicos , Fator sigma/genética , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/genética
19.
J Clin Invest ; 127(12): 4498-4515, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29130936

RESUMO

Conventional therapies for breast cancer brain metastases (BCBMs) have been largely ineffective because of chemoresistance and impermeability of the blood-brain barrier. A comprehensive understanding of the underlying mechanism that allows breast cancer cells to infiltrate the brain is necessary to circumvent treatment resistance of BCBMs. Here, we determined that expression of a long noncoding RNA (lncRNA) that we have named lncRNA associated with BCBM (Lnc-BM) is prognostic of the progression of brain metastasis in breast cancer patients. In preclinical murine models, elevated Lnc-BM expression drove BCBM, while depletion of Lnc-BM with nanoparticle-encapsulated siRNAs effectively treated BCBM. Lnc-BM increased JAK2 kinase activity to mediate oncostatin M- and IL-6-triggered STAT3 phosphorylation. In breast cancer cells, Lnc-BM promoted STAT3-dependent expression of ICAM1 and CCL2, which mediated vascular co-option and recruitment of macrophages in the brain, respectively. Recruited macrophages in turn produced oncostatin M and IL-6, thereby further activating the Lnc-BM/JAK2/STAT3 pathway and enhancing BCBM. Collectively, our results show that Lnc-BM and JAK2 promote BCBMs by mediating communication between breast cancer cells and the brain microenvironment. Moreover, these results suggest targeting Lnc-BM as a potential strategy for fighting this difficult disease.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/metabolismo , Janus Quinase 2/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Janus Quinase 2/genética , Células MCF-7 , Camundongos , Camundongos Nus , Células NIH 3T3 , Metástase Neoplásica , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Transdução de Sinais/genética , Microambiente Tumoral/genética , Células U937
20.
Adv Mater ; 29(47)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29116652

RESUMO

The recent introduction of thermally activated delayed fluorescence (TADF) emitters is regarded as an important breakthrough for the development of high efficiency organic light-emitting devices (OLEDs). The planar D and A groups are generally used to construct TADF emitters for their rigid structure and large steric hindrance. In this work, it is shown that many frequently used nonaromatic (noncontinuous conjugation or without satisfying Hückel's rule) planar segments, such as 9,9-dimethyl-9,10-dihydroacridine, are actually pseudoplanar segments and have two possible conformations-a planar form and a crooked form. Molecules constructed from pseudoplanar segments can thus have two corresponding conformations. Their existence can have significant impact on the performance of many TADF emitters. Two design strategies are presented for addressing the problem by either (1) increasing the rigidity of these groups to suppress its crooked form or (2) increasing the steric hindrance of the linked group to minimize energy of the emitters with the highly twisted form. Following these strategies, two new emitters are synthesized accordingly and successfully applied in OLEDs demonstrating high external quantum efficiencies (20.2% and 18.3%).

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