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1.
Nature ; 632(8023): 63-68, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38961303

RESUMO

Mass is commonly considered an intrinsic property of matter, but modern physics reveals particle masses to have complex origins1, such as the Higgs mechanism in high-energy physics2,3. In crystal lattices such as graphene, relativistic Dirac particles can exist as low-energy quasiparticles4 with masses imparted by lattice symmetry-breaking perturbations5-8. These mass-generating mechanisms all assume Hermiticity, or the conservation of energy in detail. Using a photonic synthetic lattice, we show experimentally that Dirac masses can be generated by means of non-Hermitian perturbations based on optical gain and loss. We then explore how the spacetime engineering of the gain and loss-induced Dirac mass affects the quasiparticles. As we show, the quasiparticles undergo Klein tunnelling at spatial boundaries, but a local breaking of a non-Hermitian symmetry can produce a new flux non-conservation effect at the domain walls. At a temporal boundary that abruptly flips the sign of the Dirac mass, we observe a variant of the time-reflection phenomenon: in the non-relativistic limit, the Dirac quasiparticle reverses its velocity, whereas in the relativistic limit, the original velocity is retained.

2.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892310

RESUMO

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.


Assuntos
Movimento Celular , Metaloproteinase 9 da Matriz , Neoplasias de Mama Triplo Negativas , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Movimento Celular/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Animais , Camundongos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Invasividade Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos Nus
3.
Cancer Sci ; 114(9): 3583-3594, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37650703

RESUMO

Radiotherapy (RT) plays an important role in localized lung cancer treatments. Although RT locally targets and controls malignant lesions, RT resistance prevents RT from being an effective treatment for lung cancer. In this study, we identified phosphomevalonate kinase (PMVK) as a novel radiosensitizing target and explored its underlying mechanism. We found that cell viability and survival fraction after RT were significantly decreased by PMVK knockdown in lung cancer cell lines. RT increased apoptosis, DNA damage, and G2/M phase arrest after PMVK knockdown. Also, after PMVK knockdown, radiosensitivity was increased by inhibiting the DNA repair pathway, homologous recombination, via downregulation of replication protein A1 (RPA1). RPA1 downregulation was induced through the ubiquitin-proteasome system. Moreover, a stable shRNA PMVK mouse xenograft model verified the radiosensitizing effects of PMVK in vivo. Furthermore, PMVK expression was increased in lung cancer tissues and significantly correlated with patient survival and recurrence. Our results demonstrate that PMVK knockdown enhances radiosensitivity through an impaired HR repair pathway by RPA1 ubiquitination in lung cancer, suggesting that PMVK knockdown may offer an effective therapeutic strategy to improve the therapeutic efficacy of RT.


Assuntos
Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Fosfotransferases (Aceptor do Grupo Fosfato) , Tolerância a Radiação/genética , Ubiquitinação , Modelos Animais de Doenças
4.
Brief Bioinform ; 22(1): 474-484, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31885044

RESUMO

BACKGROUND: With the increasing development of biotechnology and information technology, publicly available data in chemistry and biology are undergoing explosive growth. Such wealthy information in these resources needs to be extracted and then transformed to useful knowledge by various data mining methods. However, a main computational challenge is how to effectively represent or encode molecular objects under investigation such as chemicals, proteins, DNAs and even complicated interactions when data mining methods are employed. To further explore these complicated data, an integrated toolkit to represent different types of molecular objects and support various data mining algorithms is urgently needed. RESULTS: We developed a freely available R/CRAN package, called BioMedR, for molecular representations of chemicals, proteins, DNAs and pairwise samples of their interactions. The current version of BioMedR could calculate 293 molecular descriptors and 13 kinds of molecular fingerprints for small molecules, 9920 protein descriptors based on protein sequences and six types of generalized scale-based descriptors for proteochemometric modeling, more than 6000 DNA descriptors from nucleotide sequences and six types of interaction descriptors using three different combining strategies. Moreover, this package realized five similarity calculation methods and four powerful clustering algorithms as well as several useful auxiliary tools, which aims at building an integrated analysis pipeline for data acquisition, data checking, descriptor calculation and data modeling. CONCLUSION: BioMedR provides a comprehensive and uniform R package to link up different representations of molecular objects with each other and will benefit cheminformatics/bioinformatics and other biomedical users. It is available at: https://CRAN.R-project.org/package=BioMedR and https://github.com/wind22zhu/BioMedR/.


Assuntos
Biologia Computacional/métodos , Sistemas de Gerenciamento de Base de Dados , Gerenciamento de Dados/métodos , Bases de Dados de Compostos Químicos , Bases de Dados Genéticas , Humanos
5.
Cancer Cell Int ; 23(1): 172, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596639

RESUMO

BACKGROUND: The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors. METHODS: In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo. RESULTS: ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues. CONCLUSIONS: Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

6.
Int J Gynecol Cancer ; 33(8): 1279-1286, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37451690

RESUMO

OBJECTIVE: This prospective cohort study evaluated the introduction of an enhanced recovery after surgery (ERAS) pathway in a tertiary gynecologic oncology referral center. Compliance and clinical outcomes were studied in two separate surgical cohorts. METHODS: Patients undergoing laparotomy for suspected or verified advanced ovarian cancer at Oslo University Hospital were prospectively included in a pre- and post-implementation cohort. A priori, patients were stratified into: cohort 1, patients planned for surgery of advanced disease; and cohort 2, patients undergoing surgery for suspicious pelvic tumor. Baseline characteristics, adherence to the pathway, and clinical outcomes were assessed. RESULTS: Of the 439 included patients, 235 (54%) underwent surgery for advanced ovarian cancer in cohort 1 and 204 (46%) in cohort 2. In cohort 1, 53% of the patients underwent surgery with an intermediate/high Aletti complexity score. Post-ERAS, median fasting times for solids (13.1 hours post-ERAS vs 16.0 hours pre-ERAS, p<0.001) and fluids (3.7 hours post-ERAS vs 11.0 hours pre-ERAS, p<0.001) were significantly reduced. Peri-operative fluid management varied less and was reduced from median 15.8 mL/kg/hour (IQR 10.8-22.5) to 11.5 mL/kg/hour (IQR 9.0-15.4) (p<0.001). In cohort 2 only there was a statistically significant reduction in length of stay (mean (SD) 4.3±1.5 post-ERAS vs 4.6±1.2 pre-ERAS, p=0.026). Despite stable readmission rates, there were significantly more serious complications reported in cohort 1 post-ERAS. CONCLUSIONS: ERAS increased adherence to current standards in peri-operative management with significant reduction in fasting times for both solids and fluids, and peri-operative fluid administration. Length of stay was reduced in patients with suspicious pelvic tumor. Despite serious complications being common in patients with advanced disease undergoing debulking surgery, a causal relationship with the ERAS protocol could not be established. Implementing ERAS and continuous performance auditing are crucial to advancing peri-operative care of patients with ovarian cancer.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias Ovarianas , Neoplasias Pélvicas , Humanos , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/complicações , Tempo de Internação , Estudos Retrospectivos
7.
Int J Gynecol Cancer ; 33(8): 1287-1294, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37451689

RESUMO

OBJECTIVES: This study aimed to analyze the adherence to strategies to prevent post-operative nausea and vomiting after implementation of an enhanced recovery after surgery (ERAS) protocol for gynae-oncology patients. Patient-reported nausea before and after ERAS was also studied. METHODS: This prospective observational study included all patients undergoing laparotomy for a suspicious pelvic mass or confirmed advanced ovarian cancer before (pre-ERAS) and after the implementation of ERAS (post-ERAS) at Oslo University Hospital, Norway. Patients were a priori stratified according to the planned extent of surgery into two cohorts (Cohort 1: Surgery of advanced disease; Cohort 2: Surgery for a suspicious pelvic tumor). Clinical data including baseline characteristics and outcome data were prospectively collected. RESULTS: A total of 439 patients were included, 243 pre-ERAS and 196 post-ERAS. At baseline, 27% of the patients reported any grade of nausea. In the post-ERAS cohort, statistically significantly more patients received double post-operative nausea and vomiting prophylaxis (64% pre-ERAS vs 84% post-ERAS, p<0.0001). There was no difference in the need for rescue medication (82% pre-ERAS vs 79% post-ERAS; p=0.17) and no statistically significant difference between pre- and post-ERAS or between the surgical cohorts in patient-reported nausea of any grade on day 2. Patients who reported none/mild nausea on day 2 had significantly less peri-operative fluid administered during surgery than those who reported moderate or severe nausea (median 12.5 mL/kg/hour vs 16.5 mL/kg/hour, p=0.045) but, in multivariable analysis, fluid management did not remain significantly associated with nausea. CONCLUSION: Implementation of an ERAS protocol increased the adherence to post-operative nausea and vomiting prevention guidelines. Nausea, both before and after laparotomy, remains an unmet clinical need of gynae-oncology patients also in an ERAS program. Patient-reported outcome measures warrant further investigation in the evaluation of ERAS.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário , Náusea/etiologia , Náusea/prevenção & controle , Vômito , Tempo de Internação , Estudos Retrospectivos , Complicações Pós-Operatórias/prevenção & controle , Estudos Observacionais como Assunto
8.
J Acoust Soc Am ; 154(3): 1871-1881, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37756575

RESUMO

The aim of this work is to investigate and analyze the operation mechanism and power control principle of a bolted Langevin type (BLT)-loaded phase-shifted control inverter and to find a safe power control method for a phase-shifted control inverter used to drive a high-power BLT by preventing the differential current (shock current) from occurring in the right branches of a phase-shifted full-bridge circuit. In this paper, by allowing the inverter operating frequency to operate under inductive loads that coincide with the zero points of voltage and current rather than the resonant frequency of the BLT, which results in the generation of a shock current in the right branch of the full-bridge circuit, the switches of the right-branch also enabled zero-voltage, zero-current switching on (ZVZCS turn-on). The proposed method can fundamentally eliminate the generation of shock current by realizing ZVZCS turn-on on the right-branch switch elements of the inverter. The phase-shift angle control limit for power control by this scheme is 90° and the power control range is 20%-100%.

9.
Opt Express ; 30(20): 37085-37100, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258626

RESUMO

Color balance is a critical concept in the application of functional transparent polymers from a customer's standpoint. In this study, multiple polar and non-polar fluorescent dyes are embedded simultaneously for the first time in a polydimethylsiloxane (PDMS) polymer matrix. Five dyes successfully coexist with the optimum blending ratio. Furthermore, simultaneous dispersing of polar and non-polar dyes in the polymer is achieved. Absorption and photoluminescence characteristics of multiple fluorescent dyes in PDMS medium are systemically deconvoluted and discussed. The competitive average visible transmittance and color balance of synthesized multi-fluorescent dye embedded PDMS is demonstrated by high color rendering index and CIE color space coordinates close to the white point. Additionally, the luminescent solar concentrator device demonstrates improved power conversion efficiency and light utilization efficiency than the pure PDMS waveguide-based device. Moreover, the long-term storage stability is demonstrated successfully. The findings, therefore, demonstrate the applicability of multi-fluorescent dye embedded PDMS to advanced transparent devices.

10.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232715

RESUMO

PAUF, a tumor-promoting protein secreted by cancer cells, exerts paracrine effects on immune cells through TLR4 receptors expressed on immune cell surfaces. This study aimed to investigate if PAUF elicits autocrine effects on pancreatic cancer (PC) cells through TLR4, a receptor that is overexpressed on PC cells. In this study, TLR4 expression was detected in PC cells only, but not normal pancreatic cells. The migration of TLR4 high-expressing PC cells (i.e., BxPC-3) was reduced by a selective TLR4 inhibitor, in a dose-dependent manner. Using TLR4 overexpressed and knockout PC cell lines, we observed direct PAUF-TLR4 binding on the PC cell surfaces, and that PAUF-induced cancer migration may be mediated exclusively through the TLR4 receptor. Further experiments showed that PAUF signaling was passed down through the TLR4/MyD88 pathway without the involvement of the TLR4/TRIF pathway. TLR4 knockout also downregulated PC membrane PD-L1 expression, which was not influenced by PAUF. To the best of our knowledge, TLR4 is the first receptor identified on cancer cells that mediates PAUF's migration-promoting effect. The results of this study enhanced our understanding of the mechanism of PAUF-induced tumor-promoting effects and suggests that TLR4 expression on cancer cells may be an important biomarker for anti-PAUF treatment.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Fator 88 de Diferenciação Mieloide , Subunidade p50 de NF-kappa B , Neoplasias Pancreáticas , Receptor 4 Toll-Like , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Movimento Celular/genética , Movimento Celular/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lectinas/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Neoplasias Pancreáticas
11.
Mol Cancer ; 20(1): 133, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649584

RESUMO

BACKGROUND: AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined. METHODS: AMPKα1fl/flFoxp3YFP-Cre, Foxp3YFP-Cre, Rag1-/-, and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation. RESULTS: The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3ß (GSK-3ß), inhibiting the expression of PD-1 in Tregs. CONCLUSION: Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3ß signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hidroximetilglutaril-CoA Redutases/metabolismo , Imunomodulação , Receptor de Morte Celular Programada 1/genética , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Metabolismo Energético , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Imunofenotipagem , Camundongos , Receptor de Morte Celular Programada 1/metabolismo
12.
Biochem Biophys Res Commun ; 563: 15-22, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34058470

RESUMO

Helicobacter pylori infection is a crucial factor in the development of gastric cancer (GC). Molecular therapeutic targets and mechanisms contributing to H. pylori infection-associated GC induction are poorly understood and this study aimed to fill that research gap. We found that the nuclear receptor estrogen-related receptor gamma (ESRRG) is a candidate factor influencing H. pylori infection-driven GC. ESRRG suppressed H. pylori infection and cell growth induced by H. pylori infection in GC cells and organoid models In addition, H. pylori infection downregulates ESRRG expression. Gene expression profiling revealed that trefoil factor 1 (TFF1), a well-known tumor suppressor in GC, is a downstream target of ESRRG. Mechanistically, ESRRG directly binds to the TFF1 promoter and induces TFF1 gene expression. Furthermore, TFF1 activation by ESRRG was inhibited by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/p65, which is induced by inflammation, such as by H. pylori infection. Our current study provides new molecular insights into how ESRRG regulates H. pylori infection, contributing to GC development. We suggest that modulation of ESRRG-suppressing H. pylori infection could be a therapeutic target for the treatment of GC patients.


Assuntos
Infecções por Helicobacter/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias Gástricas/metabolismo , Fator Trefoil-1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Gástricas/patologia
13.
J Gastroenterol Hepatol ; 36(5): 1197-1207, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32875595

RESUMO

BACKGROUND AND AIM: This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. METHODS: A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. RESULTS: A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. CONCLUSION: Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Neoplasias Colorretais/patologia , Neoplasias Colorretais/psicologia , Neoplasias Colorretais/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Análise de Regressão , Adulto Jovem
14.
Curr Microbiol ; 78(5): 1730-1740, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33704531

RESUMO

Washing rice water (WRW) refers to the sewage produced by rice washing in China and other parts of Asia people's daily life. As in the WRW is rich a variety of nutrients, microorganisms are prone to multiply and pollute the environment. In this article, high-throughput sequencing is used to describe the microbial diversity in different fermentation time WRW. The results showed that the sequencing depth effectively covered the microbial species in the samples, and the bacterial community structure in the samples of WRW at different fermentation periods was rich in diversity. Preominant taxa included Proteobacteria (62%), Firmicutes (28%), approximately Cyanobacteria (10%) and Bacteroidetes (0.5%). The core WRW microbiome comprises Trabulsiella, Pseudomonas, Serratia, Lactobacillus, Erwinia, Enterobacter, Clostridium and Acinetobacter, some of which are potential beneficial microbes. The change of microbial community composition with the change of habitat was assessed. It was found that environmental factors had significant influence on the assembly structure of microbial community.


Assuntos
Microbiota , Oryza , China , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Água
15.
Biochem Biophys Res Commun ; 528(2): 376-382, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32087970

RESUMO

The RNA binding proteins (RBPs) have multiple roles in human cancer. However, their molecular target and function have not been clearly identified. Our genomic analysis derived from patients reveals that NONO is a potential oncogenic gene in lung cancer. NONO is highly expressed in lung cancer tissues compared with normal tissues, and its expression has been correlated with the prognosis of lung cancer patients. We found that NONO significantly influences cancer cell proliferation in lung cancer. Gene expression profiles with NONO-depleted cells revealed that the sirtuin signaling pathway is highly correlated with NONO. Thus, NONO-silenced cells caused reduction of the TCA cycle and glycolysis metabolism. We identified that NONO regulated NAMPT, which is a well-known gene involved in sirtuin signaling, and NONO has a significant correlation with NAMPT in lung cancer patients. We propose that NONO modulates energy metabolism by direct interaction with NAMPT and suggest that a functional relationship between NONO and NAMPT contributes to lung cancer cell survival. Targeting the axis can be a promising approach for patient treatment in lung cancer.


Assuntos
Citocinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Metabolismo Energético , Neoplasias Pulmonares/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Proteínas de Ligação a RNA/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Nicotinamida Fosforribosiltransferase/genética , Proteínas de Ligação a RNA/genética
16.
J Chem Inf Model ; 60(1): 63-76, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31869226

RESUMO

Lipophilicity, as evaluated by the n-octanol/buffer solution distribution coefficient at pH = 7.4 (log D7.4), is a major determinant of various absorption, distribution, metabolism, elimination, and toxicology (ADMET) parameters of drug candidates. In this study, we developed several quantitative structure-property relationship (QSPR) models to predict log D7.4 based on a large and structurally diverse data set. Eight popular machine learning algorithms were employed to build the prediction models with 43 molecular descriptors selected by a wrapper feature selection method. The results demonstrated that XGBoost yielded better prediction performance than any other single model (RT2 = 0.906 and RMSET = 0.395). Moreover, the consensus model from the top three models could continue to improve the prediction performance (RT2 = 0.922 and RMSET = 0.359). The robustness, reliability, and generalization ability of the models were strictly evaluated by the Y-randomization test and applicability domain analysis. Moreover, the group contribution model based on 110 atom types and the local models for different ionization states were also established and compared to the global models. The results demonstrated that the descriptor-based consensus model is superior to the group contribution method, and the local models have no advantage over the global models. Finally, matched molecular pair (MMP) analysis and descriptor importance analysis were performed to extract transformation rules and give some explanations related to log D7.4. In conclusion, we believe that the consensus model developed in this study can be used as a reliable and promising tool to evaluate log D7.4 in drug discovery.


Assuntos
Aprendizado de Máquina , Modelos Moleculares , Algoritmos , Descoberta de Drogas/métodos , Lipídeos/química , Relação Quantitativa Estrutura-Atividade
17.
J Korean Med Sci ; 35(5): e31, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32030920

RESUMO

BACKGROUND: Mechanism and predictive biomarkers for tyrosine kinase inhibitor (TKI) resistance of advanced clear cell renal cell carcinoma (ccRCC) have not been fully evaluated. METHODS: We performed gene expression profiling on samples from an acquired TKI resistance cohort that consisted of 10 cases of TKI-treated ccRCC patients with matched tumor tissues harvested at pre-treatment and TKI-resistant post-treatment periods. In addition, a public microarray dataset from patient-derived xenograft model for TKI-treated ccRCC (GSE76068) was retrieved. Commonly altered pathways between the datasets were investigated by Ingenuity Pathway Analysis using commonly regulated differently expressed genes (DEGs). The significance of candidate DEG on intrinsic TKI resistance was assessed through immunohistochemistry in a separate cohort of 101 TKI-treated ccRCC cases. RESULTS: TNFRSF1A gene expression and tumor necrosis factor (TNF)-α pathway were upregulated in ccRCCs with acquired TKI resistance in both microarray datasets. Also, high expression (> 10% of labeled tumor cells) of TNF receptor 1 (TNFR1), the protein product of TNFRSF1A gene, was correlated with sarcomatoid dedifferentiation and was an independent predictive factor of clinically unfavorable response and shorter survivals in separated TKI-treated ccRCC cohort. CONCLUSION: TNF-α signaling may play a role in TKI resistance, and TNFR1 expression may serve as a predictive biomarker for clinically unfavorable TKI responses in ccRCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais , Inibidores de Proteínas Quinases , Receptores Tipo I de Fatores de Necrose Tumoral , Transdução de Sinais , Fator de Necrose Tumoral alfa , Adulto , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/terapia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/diagnóstico , Neoplasias Renais/metabolismo , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Análise de Sobrevida , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
18.
Reprod Domest Anim ; 55(5): 624-631, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32108385

RESUMO

This study investigated the relationship between acrosome reactions and fatty acid composition with respect to fertility in boar sperm. The acrosome reaction was induced more than 85% by 60 mM methyl-beta-cyclodextrin (MBCD), and plasma membrane integrity was significantly reduced dependent on the MBCD level in boar sperm (p < .05). The acrosome-reacted sperm exhibited significantly higher saturated fatty acids (SFAs) and lower polyunsaturated fatty acids (PUFAs) composition compared to the non-acrosome reaction group (p < .0001). In addition, the PUFAs, C22:5n-6 (docosapentaenoic acid [DPA]; p < .01) and C22:6n-3 (docosahexaenoic acid [DHA]; p < .0001) were significantly decreased, and cleavage and blastocyst formation of oocytes were significantly (p < .0001) decreased in acrosome-reacted sperm relative to non-acrosome-reacted sperm. Moreover, acrosome reaction was positively correlated with SFAs, whereas negatively correlated with PUFAs, of the PUFAs, the DPA (p = .0005) and DHA (p = <.0001) were negatively correlated with the acrosome reaction. Therefore, these results suggest that the PUFAs composition of sperm is closely involved in acrosome reaction in pigs.


Assuntos
Reação Acrossômica/efeitos dos fármacos , Ácidos Graxos Insaturados/química , Espermatozoides/fisiologia , beta-Ciclodextrinas/farmacologia , Animais , Membrana Celular/efeitos dos fármacos , Fertilização in vitro/veterinária , Masculino , Oócitos , Espermatozoides/química , Sus scrofa
19.
Molecules ; 25(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033016

RESUMO

Vitamin E (VE) and ß-cyclodextrin (ß-CD) can form an inclusion complex; however, the inclusion rate is low because of the weak interaction between VE and ß-CD. The results of a molecular docking study showed that the oxygen atom in the five-membered ring of octenyl succinic anhydride (OSA) formed a strong hydrogen bond interaction (1.89 Å) with the hydrogen atom in the hydroxyl group of C-6. Therefore, ß-CD was modified using OSA to produce octenyl succinic-ß-cyclodextrin (OCD). The inclusion complexes were then prepared using OCD with VE. The properties of the inclusion complex were investigated by Fourier-transform infrared spectroscopy (FT-IR), 13C CP/MAS NMR, scanning electron microscopy (SEM), and atomic force microscopy (AFM). The results demonstrated that VE had been embedded into the cavity of OCD. Furthermore, the emulsifying properties (particle size distribution, ζ-potential, and creaming index) of the OCD/VE inclusion-complex-stabilized emulsion were compared with that stabilized by ß-CD, OCD, and an OCD/VE physical mixture. The results showed that the introduction of the OS group and VE could improve the physical stability of the emulsion. In addition, the OCD/VE inclusion complex showed the strongest ability to protect the oil in the emulsion from oxidation. OCD/VE inclusion complex was able to improve the physical and oxidative stability of the emulsion, which is of great significance to the food industry.


Assuntos
Emulsões/química , Conservação de Alimentos/métodos , Succinatos/química , Vitamina E/química , beta-Ciclodextrinas/química , Antioxidantes/química , Indústria Alimentícia/métodos , Peroxidação de Lipídeos/efeitos dos fármacos , Microscopia de Força Atômica , Simulação de Acoplamento Molecular , Ressonância Magnética Nuclear Biomolecular , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(3): 215-220, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32204756

RESUMO

OBJECTIVE: To study the clinical features and chest CT findings of coronavirus disease 2019 (COVID-19) in infants and young children. METHODS: A retrospective analysis was performed for the clinical data and chest CT images of 9 children, aged 0 to 3 years, who were diagnosed with COVID-19 by nucleic acid detection between January 20 and February 10, 2020. RESULTS: All 9 children had an epidemiological history, and family clustering was observed for all infected children. Among the 9 children with COVID-19, 5 had no symptoms, 4 had fever, 2 had cough, and 1 had rhinorrhea. There were only symptoms of the respiratory system. Laboratory examination showed no reductions in leukocyte or lymphocyte count. Among the 9 children, 6 had an increase in lymphocyte count and 2 had an increase in leukocyte count. CT examination showed that among the 9 children, 8 had pulmonary inflammation located below the pleura or near the interlobar fissure and 3 had lesions distributed along the bronchovascular bundles. As for the morphology of the lesions, 6 had nodular lesions and 7 had patchy lesions; ground glass opacity with consolidation was observed in 6 children, among whom 3 had halo sign, and there was no typical paving stone sign. CONCLUSIONS: Infants and young children with COVID-19 tend to have mild clinical symptoms and imaging findings not as typical as those of adults, and therefore, the diagnosis of COVID-19 should be made based on imaging findings along with epidemiological history and nucleic acid detection. Chest CT has guiding significance for the early diagnosis of asymptomatic children.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Betacoronavirus , COVID-19 , Teste para COVID-19 , Pré-Escolar , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
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