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1.
Cell ; 185(13): 2265-2278.e14, 2022 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-35568034

RESUMEN

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.


Asunto(s)
COVID-19 , Vacunas , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Ratones , SARS-CoV-2/genética
2.
Cell ; 185(10): 1728-1744.e16, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35460644

RESUMEN

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Macaca mulatta , Ratones , ARN Circular/genética , SARS-CoV-2/genética , Vacunas Sintéticas/genética , Vacunas de ARNm
3.
Nature ; 586(7830): 572-577, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32726802

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.


Asunto(s)
Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/inmunología , Neumonía Viral/prevención & control , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , COVID-19 , Vacunas contra la COVID-19 , Humanos , Macaca mulatta/inmunología , Macaca mulatta/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Animales , Modelos Moleculares , Dominios Proteicos , SARS-CoV-2 , Suero/inmunología , Bazo/citología , Bazo/inmunología , Linfocitos T/inmunología , Vacunación
4.
New Phytol ; 238(4): 1420-1430, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36843251

RESUMEN

The basal levels of salicylic acid (SA) vary dramatically among plant species. In the shoot, for example, rice contains almost 100 times higher SA levels than Arabidopsis. Despite its high basal levels, neither the biosynthetic pathway nor the biological functions of SA are well understood in rice. Combining with metabolite analysis, physiological, and genetic approaches, we found that the synthesis of basal SA in rice shoot is dependent on OsAIM1, which encodes a beta-oxidation enzyme in the phenylalanine ammonia-lyase (PAL) pathway. Compromised SA accumulation in the Osaim1 mutant led to a lower shoot temperature than wild-type plants. However, this shoot temperature defect resulted from increased transpiration due to elevated steady-state stomatal aperture in the mutant. Furthermore, the high basal SA level is required for sustained expression of OsWRKY45 to modulate the steady-state stomatal aperture and shoot temperature in rice. Taken together, these results provide the direct genetic evidence for the critical role of the PAL pathway in the biosynthesis of high basal level SA in rice, which plays an important role in the regulation of steady-state stomatal aperture to promote fitness under stress conditions.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Oryza , Oryza/metabolismo , Ácido Salicílico/metabolismo , Plantas/metabolismo , Arabidopsis/genética , Fenilanina Amoníaco-Liasa/genética , Fenilanina Amoníaco-Liasa/metabolismo , Regulación de la Expresión Génica de las Plantas , Complejos Multienzimáticos/genética , Complejos Multienzimáticos/metabolismo , Proteínas de Arabidopsis/metabolismo
5.
J Med Virol ; 95(6): e28846, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37282766

RESUMEN

Since the first SARS-CoV-2 outbreak in late 2019, the SARS-CoV-2 genome has harbored multiple mutations, especially spike protein mutations. The currently fast-spreading Omicron variant that manifests without symptoms or with upper respiratory diseases has been recognized as a serious global public health problem. However, its pathological mechanism is largely unknown. In this work, rhesus macaques, hamsters, and BALB/C mice were employed as animal models to explore the pathogenesis of Omicron (B.1.1.529). Notably, Omicron (B.1.1.529) infected the nasal turbinates, tracheae, bronchi, and lungs of hamsters and BALB/C mice with higher viral loads than in those of rhesus macaques. Severe histopathological damage and inflammatory responses were observed in the lungs of Omicron (B.1.1.529)-infected animals. In addition, viral replication was found in multiple extrapulmonary organs. Results indicated that hamsters and BALB/c mice are potential animal models for studies on the development of drugs/vaccines and therapies for Omicron (B.1.1.529).


Asunto(s)
COVID-19 , SARS-CoV-2 , Ratones , Animales , Cricetinae , Macaca mulatta , Ratones Endogámicos BALB C , Bronquios
6.
Biochem Genet ; 61(2): 725-741, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36104590

RESUMEN

Lung cancer is the most commonly diagnosed cancer and the leading reason for tumor-related mortality, while non-small cell lung cancer (NSCLC) is the most usual type of lung cancer. Circular RNAs (circRNAs) have emerged as vital regulators in the development of human cancers, including NSCLC. We aimed to explore the functions of circRNA leukemia inhibitory factor receptor (circLIFR) in NSCLC progression. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify the expression of circLIFR, microRNA-429 (miR-429), and Elav-like family member 2 (CELF2) in NSCLC tissues and cells. Cell proliferation capability of NSCLC cells was determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. The flow cytometry assay was performed to evaluate cell-cycle distribution and apoptosis of NSCLC cells. The abilities of migration and invasion were measured by transwell assay. In addition, the activities of caspase 3 and caspase 9 were measured by the assay kits. The interaction relationship between miR-429 and circLIFR or CELF2 was analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The expression levels of related proteins were examined by Western Blot assay. The xenograft experiment was established to explore the role of circLIFR in vivo. CircLIFR, circular, and stable transcript in NSCLC cells, was decreased more than 2 folds in NSCLC tissues and cells than controls (P < 0.0001). Importantly, overexpression of circLIFR impeded cell proliferation, migration, invasion, and inactivated protein kinase B (AKT)/phosphatase and tensin homolog (PTEN)-signaling pathways while enhanced apoptosis and cell-cycle arrest in NSCLC cells, which was overturned by upregulation of miR-429 or silencing of CELF2. Furthermore, the upregulation of circLIFR inhibited NSCLC tumor growth in vivo. Overexpression of circLIFR could suppress NSCLC progress by acting as a sponge of miR-429 to regulate the expression of CELF2 and PTEN/AKT-signaling pathways in NSCLC.


Asunto(s)
Proteínas CELF , Carcinoma de Pulmón de Células no Pequeñas , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular , Neoplasias Pulmonares/genética , MicroARNs/genética , Proteínas del Tejido Nervioso , Proteínas Proto-Oncogénicas c-akt , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética
7.
Sensors (Basel) ; 23(11)2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37300063

RESUMEN

Compared to fixed orthodontic appliances with brackets, thermoplastic invisible orthodontic aligners offer several advantages, such as high aesthetic performance, good comfort, and convenient oral health maintenance, and are widely used in orthodontic fields. However, prolonged use of thermoplastic invisible aligners may lead to demineralization and even caries in most patients' teeth, as they enclose the tooth surface for an extended period. To address this issue, we have created PETG composites that contain piezoelectric barium titanate nanoparticles (BaTiO3NPs) to obtain antibacterial properties. First, we prepared piezoelectric composites by incorporating varying amounts of BaTiO3NPs into PETG matrix material. The composites were then characterized using techniques such as SEM, XRD, and Raman spectroscopy, which confirmed the successful synthesis of the composites. We cultivated biofilms of Streptococcus mutans (S. mutans) on the surface of the nanocomposites under both polarized and unpolarized conditions. We then activated piezoelectric charges by subjecting the nanocomposites to 10 Hz cyclic mechanical vibration. The interactions between the biofilms and materials were evaluated by measuring the biofilm biomass. The addition of piezoelectric nanoparticles had a noticeable antibacterial effect on both the unpolarized and polarized conditions. Under polarized conditions, nanocomposites demonstrated a greater antibacterial effect than under unpolarized conditions. Additionally, as the concentration of BaTiO3NPs increased, the antibacterial rate also increased, with the surface antibacterial rate reaching 67.39% (30 wt% BaTiO3NPs). These findings have the potential for application in wearable, invisible appliances to improve clinical services and reduce the need for cleaning methods.


Asunto(s)
Nanocompuestos , Streptococcus mutans , Humanos , Biopelículas , Antibacterianos/farmacología , Antibacterianos/química , Nanocompuestos/química
8.
J Cell Mol Med ; 26(7): 1969-1978, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35229451

RESUMEN

CD44 has shown prognostic values and promising therapeutic potential in multiple human cancers; however, the effects of CD44 silencing on biological behaviors of cancer stem cells (CSCs) have not been fully understood in colorectal cancer. To examine the contribution of siRNA-induced knockdown of CD44 to the biological features of colorectal CSCs, colorectal CSCs HCT116-CSCs were generated, and CD44 was knocked down in HCT116-CSCs using siRNA. The proliferation, migration and invasion of HCT116-CSCs were measured, and apoptosis and cell-cycle analyses were performed. The sensitivity of HCT116-CSCs to oxaliplatin was tested, and xenograft tumor growth assay was performed to examine the role of CD44 in HCT116-CSCs tumorigenesis in vivo. In addition, the expression of epithelial-mesenchymal transition (EMT) markers E-cadherin, N-cadherin and vimentin was quantified. siRNA-induced knockdown of CD44 was found to inhibit the proliferation, migration and invasion, induce apoptosis, promote cell-cycle arrest at the G1/G0 phase and increase the sensitivity of HCT116-CSCs to oxaliplatin in HCT116-CSCs, and knockdown of CD44 suppressed in vivo tumorigenesis and intrapulmonary metastasis of HCT116-CSCs. Moreover, silencing CD44 resulted in EMT inhibition. Our findings demonstrate that siRNA-induced CD44 knockdown suppresses the proliferation, invasion and in vivo tumorigenesis and metastasis of colorectal CSCs by inhibiting EMT.


Asunto(s)
Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Receptores de Hialuranos , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Receptores de Hialuranos/genética , Células Madre Neoplásicas/metabolismo , ARN Interferente Pequeño/genética
9.
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33307034

RESUMEN

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.


Asunto(s)
COVID-19/transmisión , Gastroenteritis/patología , Tracto Gastrointestinal/patología , Pulmón/patología , Animales , Bronquios/metabolismo , Bronquios/patología , COVID-19/inmunología , COVID-19/metabolismo , COVID-19/patología , Prueba de Ácido Nucleico para COVID-19 , Caspasa 3/metabolismo , Citocinas/inmunología , Modelos Animales de Enfermedad , Mucosa Gástrica , Gastroenteritis/metabolismo , Gastroenteritis/virología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/metabolismo , Células Caliciformes/patología , Intestino Delgado/metabolismo , Intestino Delgado/patología , Antígeno Ki-67/metabolismo , Pulmón/diagnóstico por imagen , Pulmón/inmunología , Pulmón/metabolismo , Macaca mulatta , Mucosa Nasal , ARN Viral/aislamiento & purificación , Distribución Aleatoria , Recto/metabolismo , Recto/patología , SARS-CoV-2 , Tráquea/metabolismo , Tráquea/patología
11.
BMC Pulm Med ; 22(1): 412, 2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36357869

RESUMEN

BACKGROUND: Adenocarcinoma has long been an independent histological class of lung cancer, which leads to high morbidity and mortality. We aimed to investigate the contribution of LINC02126 in lung adenocarcinoma. METHODS: RNA sequencing data and clinical information were downloaded. Diagnostic efficiency and survival analysis of LINC02126 were performed, followed by functional analysis of genes co-expressed with LINC02126 and differentially expressed genes (DEGs) in different LINC02126 expression groups. Tumor immune microenvironment (TIME) cell infiltration and correlation analysis of tumor mutation burden were performed in different LINC02126 expression groups. RESULTS: In lung adenocarcinoma, the expression level of LINC02126 was significantly decreased. Significant expression differences of LINC02126 were found in some clinical variables, including T staging, M staging, sex, stage, and EGFR mutation. LINC02126 had potential diagnostic and prognostic value for patients. In the low LINC02126 expression group, the infiltration degree of most immune cells was significantly lower than that in the high LINC02126 expression group. Tumor mutation burden level and frequency of somatic mutation in patients with low LINC02126 expression group were significantly higher than in patients with high LINC02126 expression group. CONCLUSIONS: LINC02126 could be considered as a diagnostic, prognostic and immunotherapeutic target for lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pronóstico , Receptores ErbB/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Inmunoterapia , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/genética
12.
Med Sci Monit ; 23: 4657-4664, 2017 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-28957036

RESUMEN

BACKGROUND This study aimed to compare the efficacy and safety of vinorelbine plus cisplatin (NP regimen) vs. gemcitabine plus cisplatin (GP regimen) for treatment of metastatic TNBC after failure with anthracyclines and taxanes. MATERIAL AND METHODS A total of 48 patients with metastatic TNBC that failed in anthracyclines and taxanes treatment were enrolled and randomly grouped. Patients in the NP group (n=22) were given 25 mg/m² vinorelbine on days 1 and 8 and 25 mg/m² cisplatin on days 2-4 of each 21-day cycle, while subjects in the GP group (n=26) were administered 1000 mg/m² gemcitabine on days 1 and 8 and 25 mg/m² cisplatin on days 2-4 of each 21-day cycle. The treatment response and adverse events were compared between the 2 groups every 2 cycles. RESULTS The ORR, DCR, and median TTP were 45.5%, 77.3%, and 5 months in the NP group, and 46.2%, 80.8%, and 5.2 months in the GP group, and no significant differences were observed in ORR, DCR, and median TTP between the 2 groups (P>0.05). The major adverse events included grade I-II bone marrow inhibition, gastrointestinal reactions, and phlebitis, and a lower incidence of thrombocytopenia and rash and a higher incidence of phlebitis was found in the NP group than in the GP group (P<0.05). CONCLUSIONS Either NP or GP regimen is active and tolerated in treatment of metastatic TNBC with anthracyclines and/or taxanes resistance, which may be used as a salvage treatment for metastatic TNBC.


Asunto(s)
Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Taxoides/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Vinblastina/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Demografía , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del Tratamiento , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Vinorelbina , Gemcitabina
13.
Planta ; 240(1): 103-15, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24705986

RESUMEN

Phospholipase D (PLD) is crucial for plant responses to stress and signal transduction, however, the regulatory mechanism of PLD in abiotic stress is not completely understood; especially, in crops. In this study, we isolated a gene, TaPLDα, from common wheat (Triticum aestivum L.). Analysis of the amino acid sequence of TaPLDα revealed a highly conserved C2 domain and two characteristic HKD motifs, which is similar to other known PLD family genes. Further characterization revealed that TaPLDα expressed differentially in various organs, such as roots, stems, leaves and spikelets of wheat. After treatment with abscisic acid (ABA), methyl jasmonate, dehydration, polyethylene glycol and NaCl, the expression of TaPLDα was up-regulated in shoots. Subsequently, we generated TaPLDα-overexpressing transgenic Arabidopsis lines under the control of the dexamethasone-inducible 35S promoter. The overexpression of TaPLDα in Arabidopsis resulted in significantly enhanced tolerance to drought, as shown by reduced chlorosis and leaf water loss, higher relative water content and lower relative electrolyte leakage than the wild type. Moreover, the TaPLDα-overexpressing plants exhibited longer roots in response to mannitol treatment. In addition, the seeds of TaPLDα-overexpressing plants showed hypersensitivity to ABA and osmotic stress. Under dehydration, the expression of several stress-related genes, RD29A, RD29B, KIN1 and RAB18, was up-regulated to a higher level in TaPLDα-overexpressing plants than in wild type. Taken together, our results indicated that TaPLDα can enhance tolerance to drought and osmotic stress in Arabidopsis and represents a potential candidate gene to enhance stress tolerance in crops.


Asunto(s)
Arabidopsis/fisiología , Regulación de la Expresión Génica de las Plantas , Fosfolipasa D/genética , Transducción de Señal , Estrés Fisiológico , Triticum/enzimología , Secuencia de Aminoácidos , Arabidopsis/enzimología , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Sequías , Expresión Génica , Germinación , Datos de Secuencia Molecular , Presión Osmótica , Fosfolipasa D/metabolismo , Filogenia , Hojas de la Planta/enzimología , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/enzimología , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/fisiología , Plantas Modificadas Genéticamente , Plantones/enzimología , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/fisiología , Semillas/enzimología , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/fisiología , Análisis de Secuencia de ADN , Transgenes , Triticum/genética
14.
Genet Mol Biol ; 37(1): 73-80, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24688294

RESUMEN

WRKY transcription factors have been extensively characterized in the past 20 years, but in wheat, studies on WRKY genes and their function are lagging behind many other species. To explore the function of wheat WRKY genes, we identified a TaWRKY68 gene from a common wheat cultivar. It encodes a protein comprising 313 amino acids which harbors 19 conserved motifs or active sites. Gene expression patterns were determined by analyzing microarray data of TaWRKY68 in wheat and of orthologous genes from maize, rice and barley using Genevestigator. TaWRKY68 orthologs were identified and clustered using DELTA-BLAST and COBALT programs available at NCBI. The results showed that these genes, which are expressed in all tissues tested, had relatively higher levels in the roots and were up-regulated in response to biotic stresses. Bioinformatics results were confirmed by RT-PCR experiments using wheat plants infected by Agrobacterium tumefaciens and Blumeria graminis, or treated with Deoxynivalenol, a Fusarium graminearum-induced mycotoxin in wheat or barley. In summary, TaWRKY68 functions differ during plant developmental stages and might be representing a hub gene function in wheat responses to various biotic stresses. It was also found that including data from major cereal genes in the bioinformatics analysis gave more accurate and comprehensive predictions of wheat gene functions.

15.
Heliyon ; 10(3): e25032, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38317951

RESUMEN

In the era of big data, data processing capability is key to gaining a competitive advantage for businesses. With appropriate technical and organizational resources in place, enterprises can extract considerable value from the vast amount of available data, thereby increasing their competitive advantage. Therefore, to utilize big data resources effectively, enterprises should focus on improving the intellectual abilities of big data analysts. Big data analytics intellectual capability (BDAIC) refers to the specialized skills and knowledge that employees of the enterprise possess, including technical, technical management, business, and relational knowledge, that would enable them to use analytics tools to accomplish organizational tasks and shape the core competitiveness of an enterprise. This study constructs a theoretical model that focuses on the mediating role of person-tool fit and examines the mechanisms by which BDAIC affects an enterprise's operational performance. The results show that BDAIC, which contains four basic categories of knowledge, positively influences an enterprise's operational efficiency. Additionally, person-tool matching mediates BDAIC's effect on an enterprise's operational performance. These findings explore the latest avenues of exploration in the research paradigm of big data analytics. Furthermore, this study has important implications for practitioners trying to use big data to improve business performance.

16.
Mol Biomed ; 5(1): 30, 2024 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-39095588

RESUMEN

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.


Asunto(s)
Citocinas , Modelos Animales de Enfermedad , Huésped Inmunocomprometido , Replicación Viral , Infección por el Virus Zika , Virus Zika , Animales , Virus Zika/inmunología , Virus Zika/patogenicidad , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virología , Replicación Viral/efectos de los fármacos , Ratones , Citocinas/metabolismo , Tasa de Supervivencia , Receptor de Interferón alfa y beta/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Receptores de Interferón/deficiencia , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Receptor de Interferón gamma , Células Vero
17.
Microbiome ; 12(1): 161, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39223641

RESUMEN

BACKGROUND: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. RESULTS: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. CONCLUSION: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Heces , Microbioma Gastrointestinal , Macaca mulatta , Animales , Heces/microbiología , Fiebre Chikungunya/virología , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/genética , Disbiosis/microbiología , Inflamación , Inflamasomas/metabolismo , Modelos Animales de Enfermedad , Interleucina-17/metabolismo , Tracto Gastrointestinal/microbiología , Citocinas/metabolismo
18.
Gut Microbes ; 16(1): 2334970, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38563680

RESUMEN

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.


Asunto(s)
COVID-19 , Microbioma Gastrointestinal , Animales , SARS-CoV-2 , Virulencia , Macaca mulatta
19.
J Clin Invest ; 134(18)2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39286971

RESUMEN

Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin-like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/virología , COVID-19/metabolismo , COVID-19/genética , Animales , Ratones , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Células HEK293 , Mutación , Mutación Missense , Chlorocebus aethiops
20.
J Appl Biomater Funct Mater ; 21: 22808000231181326, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37340729

RESUMEN

The primary goal of bone tissue engineering is to fabricate scaffolds that can provide a microenvironment similar to that of natural bone. Therefore, various scaffolds have been designed to replicate the bone structure. Although most tissues exhibit complicated structures, their basic structural unit includes stiff platelets arranged in a staggered micro-array. Therefore, many researchers have designed scaffolds with staggered patterns. However, relatively few studies have comprehensively analyzed this type of scaffold. In this review, we have analyzed scientific research pertaining to staggered scaffold designs and summarized their effects on the physical and biological properties of scaffolds. Compression tests or finite element analysis are typically used to evaluate the mechanical properties of scaffolds, and most studies have performed experiments in cell cultures. Staggered scaffolds improve mechanical strength and are beneficial for cell attachment, proliferation, and differentiation in comparison with conventional designs. However, very few have been studied in vivo experiments. Additionally, studies on the effect of staggered structures on angiogenesis or bone regeneration in vivo, particularly in large animals, are required. Currently, with the prevalence of artificial intelligence (AI)-based technologies, highly optimized models can be developed, resulting in better discoveries. In the future, AI can be used to deepen our understanding on the staggered structure, promoting its use in clinical applications.


Asunto(s)
Ingeniería de Tejidos , Andamios del Tejido , Animales , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Inteligencia Artificial , Huesos , Regeneración Ósea , Porosidad
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