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1.
J Med Virol ; 95(10): e29140, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37800627

RESUMEN

The epidemic of Mpox virus (MPXV) from May 2022 was once declared as a Public Health Emergency of International Concern by the World Health Organization. Vaccines play an important role in prevention of infectious diseases, and mRNA vaccine technology was proved to be a safe and effective platform with successful application in defense of coronavirus disease 2019. In this study, based on A29L, M1R, A35R, and B6R of MPXV, we developed two MPXV mRNA vaccine candidates, designated as MPXfus and MPXmix. The MPXfus was one-component, in which these four antigen proteins were linked in tandem by flexible linker and encoded by an individual mRNA as a fusion protein. The MPXmix was multicomponent containing four mRNA, and each mRNA encoded one antigen protein respectively. Mice were immunized with equal quality of MPXfus or MPXmix, delivered by lipid nanoparticles for evaluation and comparison of the immune responses induced by these two MPXV vaccine candidates. Results of immune response analyses indicated that both MPXfus and MPXmix could elicit high-level of antigen-specific antibodies and robust cellular immune response in mice. Moreover, results of virus neutralization assays suggested that sera from MPXfus- or MPXmix-immunized mice possessed high neutralizing activities against vaccinia virus. In addition, titers of antigen-specific antibody, levels of cellular immune response, and activities of neutralizing antibody against vaccinia virus induced by MPXfus and MPXmix presented no significant difference. In summary, this study provides valuable insights for further clinical development of one-component and multicomponent mRNA vaccine candidates for the prevention of MPXV and other orthomyxoviruses.


Asunto(s)
Mpox , Animales , Ratones , Anticuerpos Neutralizantes , Virus Vaccinia/genética , Inmunidad Celular , ARN Mensajero/genética , Anticuerpos Antivirales
2.
J Enzyme Inhib Med Chem ; 38(1): 2242601, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37533352

RESUMEN

ATPase family AAA domain-containing protein 2 (ATAD2) has been emerging as a hot anti-cancer drugable target due to its oncogenic epigenetic modification closely associated with cancer cells proliferation, apoptosis, migration and drug resistance. In this study, we design a series of theophylline derivatives as novel ATAD2 inhibitors through fragment-based screening and scaffold growth strategy. A novel potent ATAD2 inhibitor (compound 19f) is discovered with an IC50 value of 0.27 µM against ATAD2, which adopts a combination of classic and atypical binding mode. Additionally, compound 19f could impede ATAD2 activity and c-Myc activation, induced significant apoptosis, and illustrated an anti-migration effect in BT-549 cells. Collectively, these results provide new enlightenment for the development of novel potent ATAD2 inhibitors for triple-negative breast cancer (TNBC) treatment.


Asunto(s)
Neoplasias , Teofilina , Humanos , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Unión al ADN/metabolismo , Adenosina Trifosfatasas/metabolismo , Proliferación Celular
3.
BMC Musculoskelet Disord ; 22(1): 535, 2021 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-34118907

RESUMEN

BACKGROUND: To determine whether multiple drilling is effective in postponing the need for total hip arthroplasty (THA) in early-stage nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: We identified 514 patients who were diagnosed with early-stage ONFH between January 2008 and December 2018. One hundred ninety-six patients underwent multiple drilling, and 318 patients had a natural course of progression. One hundred fifty-nine patients were selected for each group after case-control matching for preoperative demographics and modified Ficat and Arlet stage. The rates of THA conversion were compared. We also performed Cox regression to identify risk factors associated with THA conversion in patients who underwent multiple drilling. RESULTS: Kaplan-Meier survivorship with an endpoint of THA for nontraumatic reasons were not significantly different between the multiple drilling group (75.6, 95% confidence interval 67.8-83.4%) and the natural course group (72.2, 95% confidence interval 64.8-79.6%) at 5 years (log-rank, P = .191). In the Cox regression model, a larger extent of necrotic lesion, bone marrow edema (BME), and higher postoperative work intensity significantly increased the risk of THA conversion (P < .05). Among patients treated with autogenous bone grafting, there was a lower risk of failure in patients with necrotic lesion less than 15% (P < .05). CONCLUSIONS: Multiple drilling is not effective in reducing the rate of THA conversion in early-stage nontraumatic ONFH. The risk of conversion to THA after multiple drilling is increased by a larger extent of necrotic lesion, presence of BME, and higher postoperative work intensity in patients with early-stage ONFH. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR2000035180 ) dated 2 August 2020.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Necrosis de la Cabeza Femoral , Artroplastia de Reemplazo de Cadera/efectos adversos , Trasplante Óseo , Estudios de Casos y Controles , Cabeza Femoral/cirugía , Necrosis de la Cabeza Femoral/epidemiología , Necrosis de la Cabeza Femoral/cirugía , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
4.
J Cell Biochem ; 121(4): 2950-2961, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31709636

RESUMEN

miR-760 is downregulated in various human tumors, and fat metabolism disorder correlates with tumor progression, especially anomalism of key fat metabolic enzymes that are positively modulated by c-Myc. The aim of our study is to elucidate the presumptive molecular mechanisms of miR-760-mediated esophageal squamous cell carcinoma (ESCC) cell function and to assess the therapeutic significance of miR-760 in ESCC patients. Quantitative real-time PCR (RT-qPCR) analysis indicated that miR-760 was significantly downexpressed in ESCC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assay, and flow cytometry denoted that induced ectopic overexpression of miR-760 dramatically inhibited ESCC cells proliferation, attenuated migration, and invasion facilitated apoptosis in vitro. Mechanistically, c-Myc predicted using bioinformatics was identified as a potential target gene of miR-760 by luciferase reporter assay. Furthermore, mRNA and protein expression levels of c-Myc and key fat metabolic enzymes were downregulated with miR-760 mimics. The above investigation results, responsible for the antineoplastic properties of miR-760 in ESCC, preliminarily highlighted that the hypothetical signal amongst miR-760, c-Myc, and key fat metabolic enzymes may develop a novel diagnostic marker, therapeutic target, and independent prognostic indicator.


Asunto(s)
Tejido Adiposo/embriología , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Biología Computacional , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Luciferasas/metabolismo , Invasividad Neoplásica , Pronóstico , ARN Interferente Pequeño/metabolismo
5.
Med Sci Monit ; 24: 4128-4136, 2018 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-29909422

RESUMEN

BACKGROUND Transcription factor 21 (TCF21), a member of the class A of basic helix-loop-helix family, has been widely identified as a tumor suppressor. Growing evidence has demonstrated the downregulation of TCF21 in distinct cancers. The aim of this study was to explore the expression and biological functions of TCF21 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS TCF21 expression in esophageal cancer cell lines and carcinomas tissues were detected, and its associations with clinical characteristics were analyzed. We carried out this study of biological functions and underlying mechanisms using TE10 and KYSE510 cell lines. RESULTS TCF21 mRNA and protein expression were both downregulated in esophageal cancer tissues compared with adjacent normal tissues. Low expression of TCF21 was closely correlated with N stage. In Kaplan-Meier survival analysis, patients with lower TCF21 expression had poorer prognosis. Overexpression of TCF21 greatly inhibited the proliferation, migration, and invasion in both TE10 and KYSE510 cell lines. Furthermore, mechanistic studies showed that with TCF21 gene overexpressed, the expression of tumor suppressor Kiss-1 was upregulated and epithelial-mesenchymal transition (EMT) related proteins (E-cadherin, N-cadherin, Snail, Twist, and Vimentin) which participate in cancer cell invasion and metastasis, were reversed. CONCLUSIONS TCF21 is downregulated in ESCC, and its low expression is closely correlated with N stage and predicts a poor prognosis. TCF21 functions as a tumor suppressor in ESCC progression, and enhancement of its expression levels may be partly through promoting Kiss-1 expression to reverse EMT by modulating EMT-related gene expression. Thus, TCF21 can potentially be used as a treatment target for ESCC.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Adulto , Anciano , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/biosíntesis , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , Transición Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Kisspeptinas/biosíntesis , Kisspeptinas/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Regulación hacia Arriba
6.
J Transl Med ; 14: 47, 2016 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-26865361

RESUMEN

The repair of organs and tissues has stepped into a prospective era of regenerative medicine. However, basic research and clinical practice in the lung regeneration remains crawling. Owing to the complicated three dimensional structures and above 40 types of pulmonary cells, the regeneration of lung tissues becomes a great challenge. Compelling evidence has showed that distinct populations of intrapulmonary and extrapulmonary stem/progenitor cells can regenerate epithelia as well as endothelia in various parts of the respiratory tract. Recently, the discovery of human lung stem cells and their relevant studies has opened the door of hope again, which might put us on the path to repair our injured body parts, lungs on demand. Herein, we emphasized the role of endogenous and exogenous stem/progenitor cells in lungs as well as artificial tissue repair for the injured lungs, which constitute a marvelous toolbox for the treatment of acute lung injury. Finally, we further discussed the potential problems in the pulmonary remodeling and regeneration.


Asunto(s)
Lesión Pulmonar Aguda/terapia , Trasplante de Células Madre , Células Madre/citología , Cicatrización de Heridas , Ingeniería Genética , Humanos , Regeneración
7.
Respir Res ; 17(1): 164, 2016 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-27923370

RESUMEN

BACKGROUND: Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. METHODS: Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells. RESULTS: The results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair. Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo. It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation. CONCLUSIONS: AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.


Asunto(s)
Lesión Pulmonar Aguda/patología , Proliferación Celular , Células Epiteliales/patología , Alveolos Pulmonares/patología , Regeneración , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/fisiopatología , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Indoles/farmacología , Cinética , Lipopolisacáridos , Masculino , Piperazinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/metabolismo , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/fisiopatología , Ratas Sprague-Dawley , Regeneración/efectos de los fármacos , Transducción de Señal , Sulfonamidas/farmacología
8.
Respir Res ; 16: 140, 2015 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-26561298

RESUMEN

BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS), most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem/progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid (RA) plus simvastatin (SS) with respect to dynamics of lung repair cells as well as to elucidate the underlying mechanism. MATERIALS AND METHODS: The experimental Sprague-Dawley rats were divided randomly into normal control (control), sham operated (sham), ARDS, ARDS + vehicle and ARDS + RA + SS groups. ARDS was reproduced through hemorrhagic shock/resuscitation (shock) and subsequent intratracheal LPS (4.5 mg/kg, Escherichia coli serotype O55: B5) injection. The rats were treated by intragastric administration of RA (2 mg/kg/day) and SS (2 mg/kg/day) for 5 days in the ARDS + RA + SS group. Seven days after the first RA-SS injection, a right lower lobe of lung was sampled for histological analysis concerning systemic uniform random sampling method. Immunohistochemistry of inflation-fixed lungs for alveolar type 1 (AT1), alveolar type 2 (AT2) and Clara cells was measured by AQP5, Pro-SPC and CCSP staining respectively. The alveolar cell proliferation and apoptosis were analyzed with Ki67 staining and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method. Meanwhile, the alveolar cell numerical and surface density (alveolar cells, AT1, AT2, Clara, proliferating and apoptotic cells) were evaluated by stereology. RESULTS: RA-SS compound exerted anti-inflammatory and pro-repairing effects on respiratory tracts in ARDS induced by hemorrhagic-endotoxin shock. The numerical density and surface density of alveolar cells, AT1 cell fraction, and numerical density of AT2 and Clara cells were significantly increased after treatment with RA-SS compound in ARDS. Concurrently, the Ki67+ alveolar cells were obviously increased while the TUNEL+ alveolar cells were reduced, which was correlated with the attenuation of inflammatory injury and functional repair in injured lung tissues. CONCLUSIONS: Our data convincingly indicated that the prophylactic and therapeutic treatment of RA plus SS had obvious beneficial effect on the remodeling/regeneration of injured pulmonary tissues, suggesting that the underlying mechanisms are related to the re-balance between regeneration and apoptosis in lung stem/progenitor cells.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Pulmón/efectos de los fármacos , Regeneración/efectos de los fármacos , Simvastatina/farmacología , Células Madre/efectos de los fármacos , Tretinoina/farmacología , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/fisiopatología , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patología , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Ratas Sprague-Dawley , Células Madre/metabolismo , Células Madre/patología
9.
Cell Biol Int ; 39(11): 1348-53, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26174412

RESUMEN

In recent years, more and more research has shown that the lung is an organ of regenerative potential, with several types of stem/progenitor cells undergoing proliferation and differentiation after lung injury and participating the injury repair process. Mouse lung multipotent stem cells (MLSCs) have extensive self-renewal ability in culture and could differentiate into endothelial and lung epithelial (alveolar epithelial type 1, 2, and Clara) cells in vitro. But the research of MLSCs was limited due to its rarity. In this study, we introduced a novel microfluidic magnetic activated cell sorting system in the isolation of MLSCs. The sorted MLSCs had better viability and purity. They were identified by colony formation efficiency and differentiation ability and they have self-renewal and differentiation capacities, highlighting their stem cell properties.


Asunto(s)
Citometría de Flujo/métodos , Separación Inmunomagnética/métodos , Pulmón/citología , Técnicas Analíticas Microfluídicas/métodos , Células Madre Multipotentes/citología , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Ratones , Ratones Endogámicos C57BL
10.
Crit Care ; 19: 6, 2015 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-25572180

RESUMEN

INTRODUCTION: The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, it plays pivotal roles in the pathogenesis of sepsis in several ways. Our previous study showed that rs1800625 (-429T/C) revealed a strong clinical relevance with sepsis morbidity rate and multiple organ dysfunction syndrome (MODS) in patients with major trauma. In this study, we enlarged the sample size, added two validation populations and examined the expression of RAGE on the surface of peripheral leukocytes to ex vivo lipopolysaccharide (LPS) stimulation in subjects with different genotypes. METHODS: Rs1800625 was genotyped using pyrosequencing in 837 Chinese Han patients with major trauma in Chongqing. We then validated the clinical relevance in 340 Zhejiang and 347 Yunnan patients. The expression of RAGE on the surface of peripheral blood mononuclear cells was measured by flow cytometric analysis. RESULTS: The results indicated that rs1800625 was significantly associated with sepsis morbidity rate and MODS in patients with major trauma in the Chongqing, Zhejiang and Yunnan districts. Patients with CC genotype had lower sepsis morbidity rate and MODS after major trauma. Furthermore, patients with CC genotype had significantly higher RAGE expression (P = 0.009). CONCLUSIONS: The rs1800625 polymorphism is a functional single nucleotide polymorphism and confers host susceptibility to sepsis and MODS in patients with major trauma.


Asunto(s)
Insuficiencia Multiorgánica/genética , Traumatismo Múltiple/complicaciones , Receptor para Productos Finales de Glicación Avanzada/genética , Sepsis/genética , Adulto , Pueblo Asiatico/genética , China , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Reproducibilidad de los Resultados , Sepsis/etiología
11.
Hum Vaccin Immunother ; 20(1): 2309704, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38300140

RESUMEN

From July to September 2023, China reported over 1, 400 confirmed cases of mpox transmitted mainly through sexual contact between males. Meanwhile, the percentage of men who have sex with men at universities in southwestern China is increasing every year, which is likely to lead to a potential spread of mpox on campuses. Vaccination is an effective preventive measure against infectious diseases, this study examined the willingness of university students in Southwest China to receive the mpox vaccine and analyzed the factors influencing their decision. A cross-sectional survey was conducted among 7311 university students from 10 universities in Southwest China between August 13 and September 1, 2023. The survey revealed a hesitancy rate of 56.13% toward the mpox vaccine, with the most common reason being concerns about vaccine safety (1407/4104, 34.29%). Univariate analysis identified 13 variables that significantly differed between the vaccine acceptance and vaccine hesitancy groups. Multivariate logistic regression analyses indicated protective factors for vaccine hesitancy, such as sexually transmitted diseases, previous knowledge about mpox, frequent information about mpox, people can get reinfection of mpox, and worries about mpox endemic in China. Additionally, the confidence and convenience dimensions in the 3Cs model were identified as risk factors for mpox vaccine hesitancy. This study found a high rate of vaccine hesitancy among university students in Southwest China regarding the mpox vaccine. Collaboration between university and healthcare departments is recommended to address mpox vaccine hesitancy among college students, thereby promoting their willingness to receive the mpox vaccine.


Asunto(s)
Mpox , Minorías Sexuales y de Género , Vacuna contra Viruela , Masculino , Humanos , Estudios Transversales , Homosexualidad Masculina , Vacilación a la Vacunación , Estudiantes , China
12.
Virus Res ; 323: 198961, 2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36209918

RESUMEN

Reverse genetics system offers powerful tool for the research of RNA viruses. The infectious clones of classical swine fever virus (CSFV) were commonly constructed either in high- or low-copy number plasmids and transcribed to infectious RNA using phage RNA-polymerases. Herein, the full-length genome of CSFV Shimen strain, flanked by cytomegalovirus immediate-early (CMV) promoter (a eukaryotic RNA polymerase II promoter) sequence at the 5'-end and the hepatitis delta virus ribozyme along with the bovine growth hormone termination and polyadenylation signal sequences at the 3'-end, was packaged in bacterial artificial chromosome vector to establish a CSFV infectious clone pBAC-smCSFV. This infectious cDNA clone maintained stability after passaged 20 times in bacteria. Transfection of PK15 cells with this cDNA clone facilitated recovery of infectious progeny virus which was identical to parent virus as characterized by RT-qPCR, western blotting, indirect immunofluorescence assay, one-step growth kinetics analysis and nucleotide sequencing. Based on this CSFV infectious cDNA clone, the mCherry was inserted between viral Npro and C protein to develop reporter virus CSFV-mCherry. The mCherry was stably expressed after CSFV-mCherry was passaged 10 times in PK15 cells. Taken together, this present study develops a concise and efficient CSFV infectious cDNA clone and a reporter virus CSFV-mCherry. To the best of our knowledge, this is the first combination of CMV promoter and BAC system in construction of CSFV reverse genetics system. The CSFV infectious cDNA clone and the reporter virus will be useful in the study of CSFV virus biology, virulence determinants, molecular pathogenesis, vaccine development and virus-host interaction.

13.
ACS Biomater Sci Eng ; 9(3): 1341-1351, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36825832

RESUMEN

In this paper, we synthesized selenium nanoparticles (SeNPs) that could be effectively excited by pure yellow light (YL) source to enhance antibacterial ability. Meanwhile, YL could also play the role of anti-inflammatory and promote wound healing. In addition, in order to overcome the problem of low penetration depth of photodynamic therapy (PDT), SeNPs were encapsulated with polyethylenimine (PEI), then modified with the sound sensitive agent indocyanine green (ICG), realizing the combined photoacoustic therapy to promote the healing of wounds infected by drug-resistant bacteria. The antibacterial efficiency of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) reached more than 99% in in vitro and in vivo experiments within 10 min, which could safely and quickly kill drug-resistant bacteria to repair and heal wounds.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Nanopartículas , Selenio , Selenio/farmacología , Escherichia coli , Antibacterianos/farmacología , Luz , Bacterias , Cicatrización de Heridas
14.
Theranostics ; 13(2): 787-809, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36632213

RESUMEN

ATPase family AAA domain-containing protein 2 (ATAD2) has been widely reported to be a new emerging oncogene that is closely associated with epigenetic modifications in human cancers. As a coactivator of transcription factors, ATAD2 can participate in epigenetic modifications and regulate the expression of downstream oncogenes or tumor suppressors, which may be supported by the enhancer of zeste homologue 2. Moreover, the dominant structure (AAA + ATPase and bromine domains) can make ATAD2 a potential therapeutic target in cancer, and some relevant small-molecule inhibitors, such as GSK8814 and AZ13824374, have also been discovered. Thus, in this review, we focus on summarizing the structural features and biological functions of ATAD2 from an epigenetic modulator to a cancer therapeutic target, and further discuss the existing small-molecule inhibitors targeting ATAD2 to improve potential cancer therapy. Together, these inspiring findings would shed new light on ATAD2 as a promising druggable target in cancer and provide a clue on the development of candidate anticancer drugs.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas , Epigénesis Genética , Terapia Molecular Dirigida , Neoplasias , Humanos , Dominio AAA , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética
15.
Vaccines (Basel) ; 11(9)2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37766097

RESUMEN

With no specific antiviral drugs and preventive vaccines against Mpox virus (MPXV), the epidemic has led to the declaration of a Public Health Emergency of International Concern. As a developmental direction for new vaccines, studies of subunit vaccines based upon MPXV antigen proteins are lacking. In this study, A29L, M1R, A35R, and B6R of MPXV were expressed and purified from a prokaryotic system. The four MPXV antigen proteins in combination were mixed with aluminum hydroxide or CpG7909 as adjuvant, and subsequently used to inoculate mice. The results of enzyme-linked immunosorbent assay (ELISA), flow cytometry analyses, and enzyme-linked immunospot (ELISPOT) assays indicated that A29L, M1R, A35R, and B6R elicited high-level antigen-specific antibodies and CD4+ T cells-based cellular immune response in mice. Moreover, the results of virus neutralization assays suggested that sera from the mice immunized with four proteins elicited high neutralizing activities against the vaccinia virus. Notably, the results of ELISA, ELISPOT, and virus neutralization assays also showed that the CpG7909 adjuvant was more effective in inducing an immune response compared with the aluminum adjuvant. In summary, this study offers valuable insights for further studies of subunit vaccine candidates for the prevention of MPXV and other orthomyxoviruses.

16.
IEEE Trans Cybern ; 52(11): 11624-11638, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34097632

RESUMEN

This article is concerned with the intermittent estimator-based mixed passive and [Formula: see text] control for the high-speed train (HST) with multiple noises, actuator stochastic fault, and sensor packet loss. First, an intermittent estimator is designed to track the undetectable status of HSTs in response to only partial information available due to sensor failures. Then, two different stability criteria are developed by adopting two different Lyapunov function strategies. Simultaneously, in order to reduce the control cost and accelerate the convergence time, two different algorithms are designed. It is worth emphasizing that different from the existing results of HST subject to actuator fault, this article adopts a more flexible fault representation mode, namely, semi-Markov switching mode, which is more in line with the practical background and has a higher valuable application. Especially, the Lyapunov function designed in this article can drive the system state to decrease monotonically in both the "working interval" and the "rest interval," so as to avoid the phenomenon of state impulsive jump. Finally, through the test of HST experimental value of Japan's Shinkansen, the simulation results show the effectiveness and rationality of the proposed control method and also make a comparative analysis with related works, to prove the advantages of the control technology proposed in this article.

17.
Int J Gen Med ; 15: 4613-4623, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35535145

RESUMEN

Background: Malignant pleural mesothelioma (MPM) is a particularly fatal cancer with a median survival of less than one year. The value of single-agent checkpoint inhibitors is still obscure in MPM. We aim to reveal CUL4B prognostic role and immune infiltrates in MPM patients. Methods: CUL4B expression profile and clinical information of malignant pleura mesothelioma individuals were collected from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. Quantitative real-time PCR (qRT-PCR) analysis measured CUL4B mRNA expression in epithelioid, biphasic, sarcomatoid, and normal pleural cell lines. Results: CUL4B expression elevated in MPM and had a high diagnostic value with AUC = 0.772. Additionally, our results showed that CUL4B high expression significantly correlated with poorer outcomes in MPM. Moreover, GSEA revealed 15 KEGG pathways enriched in the CUL4B high-expression group, and 22 were exhibited in the CUL4B low-expression group. Otherwise, our results showed that CUL4B was relevant to Wnt antagonistic factors (BARX2), Insulin-like growth factor binding protein 3 (IGFBP3), and Phosphatase and tensin homolog (PTEN). In addition, our results revealed that CUL4B expression was positively linked with four types of immune cells, whereas CUL4B expression was negatively linked with three types of immune cells. Additionally, our results showed that CUL4B expression regulates T helper cells, Tcm, and Th2 cells infiltration MPM microenvironment. Finally, our results identified CUL4B high expression in MPM cell line NCI-H2052 (epithelioid), MSTO-211H (biphasic), and NCI-H28 (sarcomatoid). Conclusion: CUL4B is a valuable prognostic biomarker and a critical immune cell infiltration regulator in MPM.

18.
J Orthop Surg Res ; 17(1): 85, 2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35148802

RESUMEN

INTRODUCTION: Given the possibility of inadvertent bacterial contamination of salvaged blood, the use of cell salvage is relatively contraindicated in cases of reimplantation for chronic hip periprosthetic joint infection (PJI). However, there are no published data supporting this assertion. The purpose of the current study was to compare the reinfection rate and rate of postoperative allogeneic blood transfusion (ABT) in second-stage reimplantation for PJI with or without intraoperative cell salvage reinfusion. MATERIALS AND METHODS: We identified 125 patients who underwent two-stage exchange for chronic hip PJI between November 2012 and April 2019. The groups of patients who had (n = 61) and had not (n = 64) received intraoperative cell salvage reinfusion were compared with respect to the curative infection-free rate. Moreover, we compared the need for postoperative ABT and identified independent factors associated with ABT using multiple regression analysis. RESULTS: The log-rank survival curve with an endpoint of infection eradication failure was not significantly different between the cell salvage group (98.4%, 95% CI 95.3-99.9%) and the control group (95.3%, 95% CI 90.2-99.9%) at one year (log rank, P = .330). The rates of postoperative ABT in the cell salvage group were significantly lower than those in the control group (11.5% vs 26.6%, P = .041). In multivariable models, patient age, body mass index, preoperative hemoglobin level, and intraoperative cell salvage were independent predictors of ABT exposure (P < .05). CONCLUSIONS: The use of cell salvage during reimplantation in two-stage exchange for chronic hip PJI did not appear to increase the reinfection rate, while it significantly reduced the rate of postoperative allogeneic red blood transfusion. Greater age, lower BMI, lower preoperative hemoglobin, and non-intraoperative cell salvage reinfusion were associated with higher rate of allogeneic red blood transfusion.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Recuperación de Sangre Operatoria , Infecciones Relacionadas con Prótesis , Reimplantación , Anciano , Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/microbiología , Reinfección , Reoperación , Reimplantación/efectos adversos , Estudios Retrospectivos
19.
Front Plant Sci ; 13: 853220, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35909776

RESUMEN

Due to the rising concentration of atmospheric CO2, climate change is predicted to intensify episodes of drought. However, our understanding of how combined environmental conditions, such as elevated CO2 and drought together, will influence crop-insect interactions is limited. In the present study, the direct effects of combined elevated CO2 and drought stress on wheat (Triticum aestivum) nutritional quality and insect resistance, and the indirect effects on the grain aphid (Sitobion miscanthi) performance were investigated. The results showed that, in wheat, elevated CO2 alleviated low water content caused by drought stress. Both elevated CO2 and drought promoted soluble sugar accumulation. However, opposite effects were found on amino acid content-it was decreased by elevated CO2 and increased by drought. Further, elevated CO2 down-regulated the jasmonic acid (JA) -dependent defense, but up-regulated the salicylic acid (SA)-dependent defense. Meanwhile, drought enhanced abscisic acid accumulation that promoted the JA-dependent defense. For aphids, their feeding always induced phytohormone resistance in wheat under either elevated CO2 or drought conditions. Similar aphid performance between the control and the combined two factors were observed. We concluded that the aphid damage suffered by wheat in the future under combined elevated CO2 and drier conditions tends to maintain the status quo. We further revealed the mechanism by which it happened from the aspects of wheat water content, nutrition, and resistance to aphids.

20.
Biomater Sci ; 10(4): 939-946, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35037011

RESUMEN

During clinical surgery, bleeding that occurs in the operative region is inevitable. Due to the blood adhesion on ordinary medical gloves, it reduces surgery quality to a certain extent and even prolongs operation time. Herein, we show that medical blood-repellent gloves (MBRG) can be obtained by spraying the blood-repellent mist spray (MS) on the surface of ordinary medical gloves, which are available for immediate use in around one minute. After the modification, MBRG not only have a significantly higher blood repellent rate than that of ordinary medical gloves, but also can effectively inhibit the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and even promote the healing of infected wounds. MS is easy to prepare, low-toxic, and can be widely used on the surface of various medical gloves, such as rubber gloves, polyethylene film gloves, and nitrile gloves, which may have an impact on the development of future medical gloves.


Asunto(s)
Escherichia coli , Staphylococcus aureus , Antibacterianos , Nitrilos
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