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1.
J Nanobiotechnology ; 22(1): 368, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918787

RESUMEN

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.


Asunto(s)
Cementos para Huesos , Péptido Relacionado con Gen de Calcitonina , Fosfatos de Calcio , Osteogénesis , Porcinos Enanos , Animales , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Cementos para Huesos/farmacología , Cementos para Huesos/química , Ratones , Porcinos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Columna Vertebral/cirugía , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Línea Celular , Magnesio/farmacología , Magnesio/química
2.
Arch Virol ; 167(6): 1405-1420, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35397685

RESUMEN

Coxsackievirus A19 (CV-A19) is an enterovirus belonging to the species Enterovirus C, and the prototype strain 8663 was isolated from a patient with Guillain-Barré syndrome in Japan. In this study, we determined the complete genome sequence of a CV-A19 isolate identified in a stool sample from a child with hand, foot, and mouth disease in Xinxiang, Henan, China, in 2019 and named it CV-A19 strain 2019103106/XX/CHN/2019 - 2019103106 for short. The genome of this virus consists of 7409 nucleotides, including a 6624-nucleotide open reading frame encoding a potential polyprotein precursor of 2207 amino acids. Compared with strain 8663, strain 2019103106 showed 85.1% nucleotide sequence identity in the complete genome and 85.6% identity in the VP1 coding region, reflecting their genetic divergence. Phylogenetic analysis of strain 2019103106 and other representative EV-C strains with sequences available in the GenBank database showed that CV-A19 strains could be grouped into two clusters based on the complete or 214-nucleotide partial VP1 coding regions, and 2019103106 belonged to cluster 1, with the closest relationship to CV-A19 strain SWG82 from Shandong, China. Phylogenetic trees based on the P2 and P3 coding regions highlighted the divergence between strains 2019103106 and 8663, implying that strain 2019103106 had undergone recombination. Further recombination analysis suggested that strains V18A-like CV-A1 and BBD26-like CV-A19 probably recombined to yield strain 2019103106. The present study points out the genetic diversity of CV-A19. It expands our understanding of the evolution of the CV-A19 genome, but more genome sequences of epidemic strains are needed to explain the phylogeny and evolutionary history of CV-A19 comprehensively.


Asunto(s)
Infecciones por Coxsackievirus , Enterovirus Humano C , Enfermedad de Boca, Mano y Pie , Niño , China/epidemiología , Enterovirus Humano C/genética , Genoma Viral , Genómica , Enfermedad de Boca, Mano y Pie/genética , Humanos , Nucleótidos , Filogenia , ARN Viral/genética
3.
Int J Mol Sci ; 24(1)2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36614010

RESUMEN

Calcium phosphate cement (CPC) has been widely studied, but its lack of osteoinductivity and inadequate mechanical properties limit its application, while strontium is able to promote bone formation and inhibit bone resorption. In this study, different proportions of tristrontium silicate were introduced to create a novel strontium-modified calcium phosphate cement (SMPC). The physicochemical properties of SMPC and CPC were compared, and the microstructures of the bone cements were characterized with scanning electron microscopy assays. Then, the effect of SMPC on cell proliferation and differentiation was examined. Furthermore, local inflammatory response and osteogenesis after SMPC implantation were also confirmed in the study. Finally, a rat model of isolated vertebral defects was used to test the biomechanical properties of the cements. The results showed that SMPC has better injectability and a shorter setting time than CPC. Meanwhile, the addition of tristrontium silicate promoted the mechanical strength of calcium phosphate cement, and the compressive strength of 5% SMPC increased to 6.00 ± 0.74 MPa. However, this promotion effect gradually diminished with an increase in tristrontium silicate, which was also found in the rat model of isolated vertebral defects. Furthermore, SMPC showed a more preferential role in promoting cell proliferation and differentiation compared to CPC. Neither SMPC nor CPC showed significant inflammatory responses in vivo. Histological staining suggested that SMPCs were significantly better than CPC in promoting new bone regeneration. Importantly, this osteogenesis effect of SMPC was positively correlated with the ratio of tristrontium silicate. In conclusion, 5% SMPC is a promising substitute material for bone repair with excellent physicochemical properties and biological activity.


Asunto(s)
Cementos para Huesos , Calcio , Animales , Ratas , Cementos para Huesos/farmacología , Cementos para Huesos/química , Fosfatos de Calcio/química , Osteogénesis , Calcio de la Dieta , Silicatos , Estroncio/farmacología , Estroncio/química
4.
Wei Sheng Yan Jiu ; 49(6): 889-894, 2020 Nov.
Artículo en Zh | MEDLINE | ID: mdl-33413760

RESUMEN

OBJECTIVE: To study the effect of gas explosion on brain nerve behavior of rats in real roadway environment. METHODS: Before the gas explosion, the real gas explosion roadway environment was simulated by using the roadway and explosion test system of gas explosion test in a large coal mine in Chongqing Research Institute of China Coal Science & Technology Group, and cage fixation and explosion parameter setting were carried out. That was to use the equivalent of 9. 0% gas containing mixed air and to install special cage in roadway gas detonation distance at point 40 m, 160 m and 240 m. The SPF grade healthy adult SD male rats anesthetized with chloral hydrate were placed among them, and the rats were placed in a position that could force the head. At the same time, the trunk part below the occipital foramen and the mouth and face above the line of inner canthus were fully protected, and the gas explosion experiment was carried out. A total of 40 rats were randomly divided into four groups according to their body weight: control group, burn-blast combined injuries group(40 m), proximal group(160 m) and distance group(240 m). Ten rats in each group were placed in cages at different distance points under anesthesia except the normal control group. The general physiological behavior of the rats was observed 2 h and 7 d after the explosion, and the neurobehavioral indexes of the rats were monitored by open field behavior experiment. Gross observation and pathological examination of brain tissue were performed 7 days later. RESULTS: The spirits of the rats in the 2 h exposure group after explosion were poor, and improved slightly after 7 d. The degree of surface burn was the most serious in group 40 m. The number of urination decreased while the number of feces increased(P>0. 05). At the end of the experiment, it was found that cerebral edema and hyperemia were obvious in rats. Compared with the normal control group, the brain weight of rats in each exposure group increased, and the difference was statistically significant(P<0. 05). Pathological observation showed that the brain tissues of rats in each exposed group showed irregular and disordered arrangement of nerve cells, interstitial edema, dense and deep staining of loose nuclear chromatin, formation of dense mass and other characteristics of apoptotic cells, as well as increased glia and aggregation of inflammatory cells. At 2 d and 7 h after the explosion, compared with the control group, the resting time of the neurobehavioral indicators of rats at different distance points was significantly prolonged(P<0. 01), while the number of standing times, movement time and movement distance were significantly reduced, and the difference was statistically significant(P<0. 01). CONCLUSION: The gas explosion in real roadway environment can cause certain damage to the brain tissue of rats, and has obvious influence on its neural behavior.


Asunto(s)
Traumatismos por Explosión , Explosiones , Animales , Encéfalo , China , Masculino , Ratas , Ratas Sprague-Dawley
5.
Lab Invest ; 98(8): 1039-1051, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29765110

RESUMEN

Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high incidence of severe symptoms with pulmonary edema. Mast cells (MCs) accumulation, activation and allergic inflammation were found in the brains, lungs and skeletal muscle of mice after EV71 infection, especially in the lungs of mice. Levels of histamine, platelet-activating factor (PAF), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and noradrenaline (NA) were increased in EV71-infected lungs. In addition, EV71 infection reduced the number of pulmonary T cells, dendritic cells (DCs) and monocytes, and increased the number of lung eosinophils, Tregs and MCs. MCs number and tryptase expression in target organs or tissues posed a trend towards an increase from control to severe mice. There were positive correlations between MCs number in the brains (r = 0.701, P = 0.003), lungs (r = 0.802, P < 0.0001), skeletal muscles (r = 0.737, P = 0.001) and mean clinical score. Thus, our results suggested that MCs contributed to the pulmonary edema during EV71 infection.


Asunto(s)
Enterovirus Humano A/inmunología , Infecciones por Enterovirus/inmunología , Mastocitos/inmunología , Edema Pulmonar/inmunología , Animales , Animales Recién Nacidos , Encéfalo/inmunología , Encéfalo/metabolismo , Encéfalo/virología , Citocinas/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Enterovirus Humano A/fisiología , Infecciones por Enterovirus/metabolismo , Infecciones por Enterovirus/virología , Histamina/inmunología , Histamina/metabolismo , Humanos , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/virología , Mastocitos/metabolismo , Mastocitos/virología , Ratones Endogámicos BALB C , Músculo Esquelético/inmunología , Músculo Esquelético/metabolismo , Músculo Esquelético/virología , Edema Pulmonar/metabolismo , Edema Pulmonar/virología , Factor A de Crecimiento Endotelial Vascular/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismo
6.
ACS Biomater Sci Eng ; 10(5): 3203-3217, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38557027

RESUMEN

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.


Asunto(s)
Encéfalo , Hidrogeles , Células Madre Pluripotentes Inducidas , Organoides , Médula Espinal , Organoides/efectos de los fármacos , Organoides/citología , Organoides/metabolismo , Humanos , Animales , Médula Espinal/citología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Encéfalo/metabolismo , Ratas , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacología , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Laminina/farmacología , Laminina/química , Proteoglicanos/química , Ratas Sprague-Dawley , Combinación de Medicamentos , Colágeno
7.
ACS Biomater Sci Eng ; 10(5): 3218-3231, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38593429

RESUMEN

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.


Asunto(s)
Diferenciación Celular , Matriz Extracelular Descelularizada , Hidrogeles , Células Madre Pluripotentes Inducidas , Organoides , Placenta , Médula Espinal , Humanos , Organoides/citología , Organoides/metabolismo , Organoides/efectos de los fármacos , Femenino , Placenta/citología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Embarazo , Hidrogeles/química , Hidrogeles/farmacología , Médula Espinal/citología , Médula Espinal/metabolismo , Diferenciación Celular/efectos de los fármacos , Matriz Extracelular Descelularizada/farmacología , Matriz Extracelular Descelularizada/química , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Laminina/farmacología , Laminina/química
8.
Int J Biol Macromol ; 253(Pt 1): 126601, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37652326

RESUMEN

Co-based catalysts play a crucial role in the activation of peroxymonosulfate (PMS) for degradation contaminants. However, the practical application of such catalysts is hindered by challenges like the self-aggregation of Co nanoparticles and leaching of Co2+. In this study, the Co-based catalyst Co-N/C@CL was synthesized from carboxymethylated lignin obtained by grafting abundant carboxymethyl groups into alkali lignin, in which the presence of these carboxymethyl groups enhanced its water solubility and allowed the formation of stable macromolecular complexes with Co2+. This catalyst exhibited a high specific surface area (521.8 m2·g-1) and a uniform distribution of Co nanoparticles. Consequently, the Co-N/C@CL/PMS system could completely remove 20 ppm tetracycline (TC) in 2 min at a rate of 2.404 min-1. Experimental results and DFT calculations revealed that the synergistic effect of lignin carbon and Co NPs accelerated the cleavage and electron transfer of OO bonds, thus promoting the formation of 1O2, OH and SO4-, with 1O2 emerging as the predominant contributor. Moreover, Co-N/C@CL displayed excellent cycling stability and low Co2+ leaching. This work not only provides a feasible strategy for the preparation of highly active and stable Co-based carbon materials but also offers a promising catalyst for the efficient degradation of TC.


Asunto(s)
Antibacterianos , Lignina , Tetraciclina , Carbono , Nitrógeno
9.
Infect Drug Resist ; 14: 2809-2821, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34321897

RESUMEN

OBJECTIVE: The high morbidity, complex seasonality, and recurring risk of hand-foot-and-mouth disease (HFMD) exert a major burden in China. Forecasting its epidemic trends is greatly instrumental in informing vaccine and targeted interventions. This study sets out to investigate the usefulness of an advanced exponential smoothing state space framework by combining Box-Cox transformations, Fourier representations with time-varying coefficients and autoregressive moving average (ARMA) error correction (TBATS) method to assess the temporal trends of HFMD in China. METHODS: Data from January 2009 to December 2019 were drawn, and then they were split into two segments comprising the in-sample training data and out-of-sample testing data to develop and validate the TBATS model, and its fitting and forecasting abilities were compared with the most frequently used seasonal autoregressive integrated moving average (SARIMA) method. RESULTS: Following the modelling procedures of the SARIMA and TBATS methods, the SARIMA (1,0,1)(0,1,1)12 and TBATS (0.024, {1,1}, 0.855, {<12,4>}) specifications were recognized as being the optimal models, respectively, for the 12-step ahead forecasting, along with the SARIMA (1,0,1)(0,1,1)12 and TBATS (0.062, {1,3}, 0.86, {<12,4>}) models as being the optimal models, respectively, for the 24-step ahead forecasting. Among them, the optimal TBATS models produced lower error rates in both 12-step and 24-step ahead forecasting aspects compared to the preferred SARIMA models. Descriptive analysis of the data showed a significantly high level and a marked dual seasonal pattern in the HFMD morbidity. CONCLUSION: The TBATS model has the capacity to outperform the most frequently used SARIMA model in forecasting the HFMD incidence in China, and it can be recommended as a flexible and useful tool in the decision-making process of HFMD prevention and control in China.

10.
Int J Biol Macromol ; 154: 1194-1204, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31726153

RESUMEN

A lignin-based biosorbent (LSMA) was prepared by cross-linking lignosulfonate and N-methylaniline with the aid of ammonium persulfate for efficient removal of Cr(VI) from aqueous solution. Since LSMA possessed both amino groups and oxygen-containing functional groups, such as phenolic, carboxyl, and sulfonic groups, the maximum adsorption capacity of 1264.8 mg/g was achieved at 318 K according to the Langmuir isotherm. LSMA also showed excellent performance at low Cr(VI) concentration solution. The hazardous Cr(VI) solution of 50 mg/L can be fully removed within 10 min. The adsorption process of LSMA fitted the pseudo-second-order kinetic model, suggesting the chemical adsorption characteristics. Moreover, the adsorption process was spontaneous and endothermic. LSMA worked very well even with high content of competing anions. The removal mechanism was demonstrated to be the adsorption of Cr(VI) anions on LSMA with abundant functional groups, and reduction of Cr(VI) to less toxic Cr(III) by the adjacent electron donor groups. The generated Cr(III) was immobilized on LSMA by surface complexation and precipitation. LSMA composite has a great potential for the treatment of Cr(VI)-contaminated water.


Asunto(s)
Compuestos de Anilina/química , Cromo/química , Lignina/análogos & derivados , Contaminantes Químicos del Agua/química , Adsorción , Cinética , Lignina/química , Purificación del Agua
11.
PLoS One ; 14(5): e0216993, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31120941

RESUMEN

Hand, foot and mouth disease (HFMD) is an infectious disease that affects mostly children. The children with HFMD also have other immune and metabolic disorders. However, the association of these disorders with the severity of HFMD has not yet been determined. In this study, we used a case-control study design to examine the correlation of immune and metabolic disorders with HFMD development in children. 406 mild and severe patients were recruited and divided into different subgroups based on the number of days from the initial onset time to hospitalization (1, 2, 3, 4, and ≥5 days). Logistic regression model was used to define the predictors of severe HFMD. We found that the patients from rural area (OR = 1.76, 95% CI [1.19~2.63], P = 0.005) or with body temperature of >39°C (OR = 2.14, 95% CI [1.12~4.12], P = 0.022) exhibited higher risk for severe symptoms. In addition, the risk increased with the rise of body temperature by using a Chis-quare trend test (P = 0.01). We also found that a decreased number of eosinophils was an predictor of severe HFMD at 1, 2, 3,and 4 days post infection (dpi). Decreased levels of Na+, Cl-, and creatine kinase were also predictors at 1 and ≥5 dpi. On the other hand, elevated level of globulin was a predictor for severe HFMD at 4 dpi and ≥5 dpi, and the increased number of neutrophils or increased level of alkaline phosphatase posed risk for severe HFMD at 3 and ≥5 dpi. Our results suggested that rural living, hyperpyrexia, changes in the immune system that include the numbers of eosinophils and neutrophils and the levels of IgG and globulin, and metabolic alterations, such as the levels of alkaline phosphatase, Na+, Cl-, and creatine kinase in peripheral blood are predictors of severe HFMD.


Asunto(s)
Enfermedad de Boca, Mano y Pie/diagnóstico , Enfermedad de Boca, Mano y Pie/inmunología , Adolescente , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Temperatura Corporal , Estudios de Casos y Controles , Niño , China , Cloruros/sangre , Eosinófilos/metabolismo , Femenino , Globulinas/análisis , Enfermedad de Boca, Mano y Pie/sangre , Hospitalización , Humanos , Sistema Inmunológico , Inmunoglobulina G/sangre , Inflamación/sangre , Masculino , Análisis Multivariante , Análisis de Regresión , Factores de Riesgo , Población Rural , Sodio/sangre , Adulto Joven
12.
Viruses ; 10(4)2018 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-29597291

RESUMEN

Enterovirus 71 (EV71) infection has become a major threat to global public health, especially in infants and young children. Epidemiological studies have indicated that EV71 infection is responsible for severe and even fatal cases of hand, foot, and mouth disease (HFMD). Accumulated evidence indicates that EV71 infection triggers a plethora of interactive signaling pathways, resulting in host immune evasion and inflammatory response. This review mainly covers the effects of EV71 infection on major antiviral and inflammatory cellular signal pathways. EV71 can activate cellular signaling networks including multiple cell surface and intracellular receptors, intracellular kinases, calcium flux, and transcription factors that regulate antiviral innate immunity and inflammatory response. Cellular signaling plays a critical role in the regulation of host innate immune and inflammatory pathogenesis. Elucidation of antiviral and inflammatory cellular signaling pathways initiated by EV71 will not only help uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will also provide clues for the design of therapeutic strategies against EV71 infection.


Asunto(s)
Resistencia a la Enfermedad/inmunología , Enterovirus Humano A/inmunología , Infecciones por Enterovirus/inmunología , Infecciones por Enterovirus/metabolismo , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata , Transducción de Señal , Animales , Biomarcadores , Enterovirus Humano A/genética , Infecciones por Enterovirus/virología , Humanos , Evasión Inmune , FN-kappa B/metabolismo , Estrés Oxidativo , Receptores Toll-Like/metabolismo , Proteínas Virales/metabolismo
13.
Front Microbiol ; 9: 2422, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30349526

RESUMEN

Enterovirus (EV) infections are a major threat to global public health, and are responsible for mild respiratory illness, hand, foot, and mouth disease (HFMD), acute hemorrhagic conjunctivitis, aseptic meningitis, myocarditis, severe neonatal sepsis-like disease, and acute flaccid paralysis epidemic. Among them, HFMD is a common pediatric infectious disease caused by EVs of the family Picornaviridae including EV-A71, coxsackieviruses (CV)-A2, CV-A6, CV-A10, and CV-A16. Due to lack of vaccines and specific antiviral therapeutics, millions of children still suffer from HFMD. Innate immune system detects foreign invaders by means of a relatively limited number of sensors, such as pattern recognition receptors (PRRs) [e.g., retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), Toll-like receptors (TLRs), and NOD-like receptors (NLRs)] and even some secreted functional proteins. However, a range of research, highlighted in this review, suggest that EV-associated with HFMD have evolved different strategies to avoid detection by innate immunity via different proteases (e.g., 2A, 3C, 2C, and 3D). Ongoing efforts to better understand virus-host interactions that control innate immunity and then distill how that influences HFMD development promises to have real-world significance. In this review, we address this complex topic in nine sections including multiple proteins associated with PRR and type I interferon (IFN) signaling. Recognizing how EVs linked to HFMD evade host innate immune system, we also describe the interactions between them and, finally, suggest future directions to better inform drug development and public health.

14.
Viruses ; 10(10)2018 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-30314355

RESUMEN

Enterovirus 71 (EV71) is the main pathogen of severe hand-foot-mouth disease (HFMD). Long non-coding RNAs (lncRNAs) are recognized as pivotal factors during the pathogenesis of viral infection. However, the critical functions of lncRNAs in EV71⁻host interactions have not been characterized. Here, for the first time, we performed global transcriptome analysis of lncRNA and mRNA expression profiles in EV71-infected human rhabdomyosarcoma (RD) cells and skeletal muscle of mice using second-generation sequencing. In our study, a total of 3801 novel lncRNAs were identified. In addition, 23 lncRNAs and 372 mRNAs exhibited remarkable differences in expression levels between infected and uninfected RD cells, while 104 lncRNAs and 2647 mRNAs were differentially expressed in infected skeletal muscle from neonatal mice. Comprehensive bioinformatics analysis included target gene prediction, lncRNA­mRNA co-expression network construction, as well as gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis mainly focused on differentially-expressed genes (DEGs). Our results suggest that lncRNAs may participate in EV71 infection-induced pathogenesis through regulating immune responses, protein binding, cellular component biogenesis and metabolism. The present study provides novel insights into the functions of lncRNAs and the possible pathogenic mechanism following EV71 infection.


Asunto(s)
Enterovirus Humano A/fisiología , Infecciones por Enterovirus/genética , Músculo Esquelético/virología , ARN Largo no Codificante/genética , Rabdomiosarcoma/genética , Animales , Enterovirus Humano A/genética , Infecciones por Enterovirus/metabolismo , Infecciones por Enterovirus/virología , Perfilación de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos BALB C , Músculo Esquelético/metabolismo , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Rabdomiosarcoma/metabolismo , Rabdomiosarcoma/virología , Análisis de Secuencia de ARN
15.
Oncotarget ; 8(46): 81014-81026, 2017 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-29113363

RESUMEN

Enterovirus71 (EV71) is recognized as the main causative agent of severe hand, foot and mouth disease (HFMD). However, the pathogenesis of EV71 infection has not been well characterized. Clinical evidence indicated that inducible nitric oxide synthase (iNOS) induction in the lung of HFMD patients contributes to the severe symptoms of pulmonary edema. In the present study, we recruited 142 subjects including HFMD patients and controls, and serum level of nitric oxide (NO) was determined. Next, cellular and animal model were used to further investigate the roles of iNOS and mitochondria damage during EV71 infection. Serum NO level in HFMD patients with mild or severe symptoms was higher than that in controls, and there was a trend towards an increase in the serum NO level of severe cases relative to mild cases. EV71 infection caused apoptosis and increased levels of NO, iNOS, superoxide dismutase (SOD) activity and malondialdehyde (MDA), and degraded mitochondrial membrane potential (ΔΨm) in vitro. Pathological alterations of mitochondrial morphology were observed in vitro and in vivo. Furthermore, the expression of iNOS levels in target organs including brain, spinal cord, skeletal muscle, lung and heart were increased with the progression of the pathogenesis of EV71 infection in mice. Taken together, iNOS and mitochondrial damage participate in the pathogenesis of EV71 infection.

16.
Arch Oral Biol ; 71: 150-154, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27505035

RESUMEN

OBJECTIVE: To evaluate the effects of mouse embryonic palatal mesenchymal (MEPM) cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced. STUDY DESIGN: An experimental study at Xinxiang Medical University. METHODS: Primary MEPM cells were derived from palatal tissue on 30 pregnant C57BL/6 female mice (embryonic day13, GD13). The MEPM cells were placed in a humidified incubator at 37°C with 5% CO2 atmosphere with media replaced every other day. The third passage cells were seeded, and one part of cells were treated with 10nM TCDD (TCDD group). And others were treated with DMSO (≤0.05%, as control group). After 72h, MTT assay was analysed cell viability. Scratch wound-healing was analysed cell motility. Flow cytometry was analysed cell apoptosis and cycle. Western blot was analysed the expression of cyclinE, CDK2, P16 and P21. RESULTS: TCDD inhibited the growth and migration of MEPM cells, while increased cell apoptosis. TCDD exposure inhibited the progression of cells from G1 to S phase and tended to reduce the number of cells entering the G2/M phase. TCDD inhibited expression of cyclinE and CDK2 at the protein level, instead increased the expression of P16 and p21 proteins. CONCLUSIONS: TCDD might induce cleft palate by altering MEPM cells.


Asunto(s)
Fisura del Paladar/inducido químicamente , Células Madre Mesenquimatosas/efectos de los fármacos , Hueso Paladar/embriología , Dibenzodioxinas Policloradas/toxicidad , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Citometría de Flujo , Ratones , Ratones Endogámicos C57BL , Embarazo
17.
Spine (Phila Pa 1976) ; 40(1): E1-8, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25341974

RESUMEN

STUDY DESIGN: Biomechanical in vitro study. OBJECTIVE: To determine whether the peak pull-out force (PPF) of cervical anterior transpedicular screw (ATPS) fixed in osteoporotic vertebrae positively influence screw stability or not before and after fatigue. SUMMARY OF BACKGROUND DATA: Multilevel cervical spine procedures with osteoporosis can challenge the stability of current screw-and-plate systems. A second surgical posterior approach is coupled with potential risks of increased morbidity and complications. Hence, anterior cervical instrumentation that increases primary construct stability, while avoiding the need for posterior augmentation, would be valuable. METHODS: Sixty formalin-fixed vertebrae at different levels were randomly selected. The vertebrae were divided into healthy controls (groups A1, A2), osteoporotic controls (B1, B2), healthy ATPS groups (C1, C2), osteoporotic ATPS groups (D1, D2), and osteoporotic restoration controls (E1, E2). The procedure of ATPS insertion was simulated with 2 pilot holes being drilled on each side of 20 vertebral bodies that were implanted with either vertebral screw or polymethylmethacrylate. Each side randomly received either instant PPF or PPF beyond fatigue (2.5 Hz; 20,000 times). RESULTS: The prefatigue PPFs were significantly higher than the postfatigue PPFs in all groups (group A: 366.06 ± 58.78 vs. 248.93 ± 57.21 N; group B: 275.58 ± 23.18 vs. 142.79 ± 44.78 N; group C: 635.99 ± 185.28 vs. 542.57 ± 136.58 N; group D: 519.22 ± 122.12 vs. 393.16 ± 192.07 N, and group E: 431.78 ± 75.77 vs. 325.74 ± 95.10 N). The postfatigue PPFs were reduced by 32.00% (group A), 48.19% (group B), 14.69% (group C), 24.28% (group D), and 24.72% (group E). The acute and postfatigue PPFs of both control groups were significantly lower than that of ATPS groups (P < 0.05). The cyclic osteoporosis ATPS group achieved the same PPF compared with the vertebral restoration screw group. CONCLUSION: The findings of this study suggest that instant PPF and fatigue resistance capability of an ATPS fixation were significantly better than other control groups, especially in the osteoporotic vertebrae.


Asunto(s)
Tornillos Óseos , Vértebras Cervicales/cirugía , Osteoporosis/complicaciones , Falla de Prótesis , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Cementos para Huesos/uso terapéutico , Placas Óseas , Cadáver , Humanos , Ensayo de Materiales , Persona de Mediana Edad , Procedimientos Ortopédicos/métodos , Polimetil Metacrilato/uso terapéutico , Estrés Mecánico , Adulto Joven
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 33(12): 1783-6, 2013 Dec.
Artículo en Zh | MEDLINE | ID: mdl-24369245

RESUMEN

OBJECTIVE: To investigate the presence of miRNA-144 in the saliva of patients with esophageal cancer and its value for early diagnosis of esophageal cancer. METHODS: Saliva samples were collected form patients with esophageal cancer admitted in the Fourth Affiliated Hospital of Jinan University and the First Affiliated Hospital of Guangzhou Medical College between January, 2011 and May, 2013, with saliva samples from 50 middle-aged healthy volunteers matched for age and gender ratio as the control group. The contents of miRNA-144 in the samples were detected with RT-PCR. RESULTS: The levels of miRNA-144 in both the whole saliva and saliva supernatant were significantly higher in esophageal cancer group than in the control group (P<0.05). In the whole saliva, the cut-off point of miRNA-144 was ≥100, with a sensitivity of 74.6% and a specificity of 92.0% for esophageal cancer diagnosis (Az=0.865); in saliva supernatant, the cut-off point was ≥20 with a sensitivity of 53.7% and a specificity of 94.0% (Az=0.754), suggesting a moderate diagnostic value of miRNA-144 in whole saliva and saliva supernatant. CONCLUSION: miRNA-144 is highly expressed in the saliva of patients with esophageal cancer and can be used as a genetic marker for early diagnosis of esophageal cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Esofágicas/diagnóstico , MicroARNs/análisis , Saliva/química , Diagnóstico Precoz , Humanos , Persona de Mediana Edad , Sensibilidad y Especificidad
19.
Dent Mater ; 28(10): 1071-9, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22796038

RESUMEN

OBJECTIVE: To investigate the reinforcement of Bis-GMA/TEGDMA dental resins (without conventional glass filler) and the corresponding composites (with conventional glass filler) containing varied mass fractions of halloysite nanotubes (HNTs). METHODS: Three dispersion methods were studied to separate the silanized halloysite as individual HNTs and to uniformly distribute them into dental matrices. Photopolymerization induced volumetric shrinkage was measured by using a mercury dilatometer. Real time near infrared spectroscopy was adopted to study the degree of vinyl double bond conversion and the photopolymerization rate. Mechanical properties of the composites were tested by a universal mechanical testing machine. Analysis of variance (ANOVA) was used for the statistical analysis of the acquired data. Morphologies of halloysite/HNTs and representative fracture surfaces of the reinforced dental resins/composites were examined by SEM and TEM. RESULTS: Impregnation of small mass fractions (e.g., 1% and 2.5%) of the silanized HNTs in Bis-GMA/TEGDMA dental resins/composites improved mechanical properties significantly; however; large mass fractions (e.g., 5%) of impregnation did not further improve the mechanical properties. The impregnation of HNTs into dental resins/composites could result in two opposite effects: the reinforcing effect due to the highly separated and uniformly distributed HNTs, and the weakening effect due to the formation of HNT agglomerates/particles. SIGNIFICANCE: Uniform distribution of a small amount of well-separated silanized HNTs into Bis-GMA/TEGDMA dental resins/composites could result in substantial improvements on mechanical properties.


Asunto(s)
Silicatos de Aluminio/química , Bisfenol A Glicidil Metacrilato/química , Resinas Compuestas/síntesis química , Vidrio/química , Nanotubos/química , Ácidos Polimetacrílicos/química , Análisis de Varianza , Dureza , Curación por Luz de Adhesivos Dentales , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Polimerizacion , Espectroscopía Infrarroja Corta
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