RESUMEN
Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1-like protein 3 (ORMDL3) and lead to NOD-like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV-induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV-bronchiolitis follow-up. In BEAS-2B, ORMDL3-induced NLRP3 inflammasome expression. BEAS-2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3-small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.
Asunto(s)
Asma , Bronquiolitis , Infecciones por Virus Sincitial Respiratorio , Animales , Humanos , Lactante , Ratones , Acetilación , Asma/metabolismo , Histonas/metabolismo , Inflamasomas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR , Ruidos Respiratorios , Infecciones por Virus Sincitial Respiratorio/genética , Infecciones por Virus Sincitial Respiratorio/metabolismo , Masculino , Femenino , Línea CelularRESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease in preterm infants with pathological characteristics of arrested lung development. DNA double-strand breaks (DSBs) are a serious manifestation of oxidative stress damage, but little is known about the role of DSBs in BPD. The current study set out to detect DSB accumulation and cell cycle arrest in BPD and study the expression of genes related to DNA damage and repair in BPD through DNA damage signaling pathway-based PCR array to determine a suitable target to improve arrested lung development associated with BPD. METHODS: DSB accumulation and cell cycle arrest were detected in a BPD animal model and primary cells, then a DNA damage signaling pathway-based PCR array was used to identify the target of DSB repair in BPD. RESULTS: DSB accumulation and cell cycle arrest were shown in BPD animal model, primary type II alveolar epithelial cells (AECII) and cultured cells after exposure to hyperoxia. Of the 84 genes in the DNA damage-signaling pathway PCR array, eight genes were overexpressed and 11 genes were repressed. Rad1, an important protein for DSB repair, was repressed in the model group. Real-time PCR and western blots were used to verify the microarray results. Next, we confirmed that silencing Rad1 expression aggravated the accumulation of DSBs and cell cycle arrest in AECII cells, whereas its overexpression alleviated DSB accumulation and cell cycle arrest. CONCLUSIONS: The accumulation of DSBs in AECII might be an important cause of alveolar growth arrest associated with BPD. Rad1 could be an effective target for intervention to improve this arrest in lung development associated with BPD.
Asunto(s)
Displasia Broncopulmonar , Exonucleasas , Paro Cardíaco , Animales , Ratas , Células Epiteliales Alveolares , Displasia Broncopulmonar/genética , Puntos de Control del Ciclo Celular/genética , ADN , Roturas del ADN de Doble CadenaRESUMEN
BACKGROUND: the present study aimed to describe the characteristics of articles that had the most citations in the field of digestive endoscopy. METHOD: articles included were obtained from the Web of Science database, which were selected and ranked according to the number of citations. The characteristics of the 100 most cited articles were then analyzed. RESULTS: the number of citations of the top 100 of 303,063 eligible papers ranged from 370 to 2,866. The most cited paper was a study of colorectal cancer prevention using colonoscopic polypectomy. The most common topics discussed by the top 100 papers included colonoscopy (n = 33) and upper gastrointestinal endoscopy (n = 23), with most of the papers focusing on diagnosis (n = 24) and treatment (n = 15). CONCLUSION: by identifying the most influential publications, the present study could serve as a guide toward further development in the area of digestive endoscopy.
Asunto(s)
Bibliometría , Colonoscopía , Bases de Datos Factuales , HumanosRESUMEN
BACKGROUND: Simple bone cysts, also known as a unicameral bone cysts or solitary bone cysts, are the most common type of benign bone lesion in growing children. Cysts may lead to repeated pathological fracture (fracture that occurs in an area of bone weakened by a disease process). Occasionally, these fractures may result in symptomatic malunion. The main goals of treatment are to decrease the risk of pathological fracture, enhance cyst healing and resolve pain. Despite the numerous treatment methods that have been used for simple bone cysts in long bones of children, there is no consensus on the best procedure. This is an update of a Cochrane review first published in 2014. OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating simple bone cysts in the long bones of children, including adolescents.We intended the following main comparisons: invasive (e.g. injections, curettage, surgical fixation) versus non-invasive interventions (e.g. observation, plaster cast, restricted activity); different categories of invasive interventions (i.e. injections, curettage, drilling holes and decompression, surgical fixation and continued decompression); different variations of each category of invasive intervention (e.g. different injection substances: autologous bone marrow versus steroid). SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the China National Knowledge Infrastructure Platform, trial registers, conference proceedings and reference lists. Date of last search: April 2016. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials evaluating methods for treating simple bone cysts in the long bones of children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results and performed study selection. We resolved differences in opinion between review authors by discussion and by consulting a third review author. Two review authors independently assessed risk of bias and data extraction. We summarised data using risk ratios (RRs) or mean differences (MDs), as appropriate, and 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the overall quality of the evidence. MAIN RESULTS: In this update in 2017, we did not identify any new randomised controlled trials (RCT) for inclusion. We identified one ongoing trial that we are likely to include in a future update. Accordingly, our results are unchanged. The only included trial is a multicentre RCT conducted at 24 locations in North America and India that compared bone marrow injection with steroid (methylprednisolone acetate) injection for treating simple bone cysts. Up to three injections were planned for participants in each group. The trial involved 90 children (mean age 9.5 years) and presented results for 77 children at two-year follow-up. Although the trial had secure allocation concealment, it was at high risk of performance bias and from major imbalances in baseline characteristics. Reflecting these study limitations, we downgraded the quality of evidence by two levels to 'low' for most outcomes, meaning that we are unsure about the estimates of effect. For outcomes where there was serious imprecision, we downgraded the quality of evidence by a further level to 'very low'.The trial provided very low quality evidence that fewer children in the bone marrow injection group had radiographically assessed healing of bone cysts at two years than in the steroid injection group (9/39 versus 16/38; RR 0.55 favouring steroid injection, 95% CI 0.28 to 1.09). However, the result was uncertain and may be compatible with no difference or small benefit favouring bone marrow injection. Based on an illustrative success rate of 421 children with healed bone cysts per 1000 children treated with steroid injections, this equates to 189 fewer (95% CI 303 fewer to 38 more) children with healed bone cysts per 1000 children treated with bone marrow injections. There was low quality evidence of a lack of difference between the two interventions at two years in functional outcome, based on the Activity Scale for Kids function score (0 to 100; higher scores equate to better outcome: MD -0.90; 95% CI -4.26 to 2.46) or in pain assessed using the Oucher pain score. There was very low quality evidence of a lack of differences between the two interventions for adverse events: subsequent pathological fracture (9/39 versus 11/38; RR 0.80, 95% CI 0.37 to 1.70) or superficial infection (two cases in the bone marrow group). Recurrence of bone cyst, unacceptable malunion, return to normal activities, and participant satisfaction were not reported. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine the relative effects of bone marrow versus steroid injections, although the bone marrow injections are more invasive. Noteably, the rate of radiographically assessed healing of the bone cyst at two years was well under 50% for both interventions. Overall, there is a lack of evidence to determine the best method for treating simple bone cysts in the long bones of children. Further RCTs of sufficient size and quality are needed to guide clinical practice.
Asunto(s)
Quistes Óseos/terapia , Trasplante de Médula Ósea/métodos , Glucocorticoides/administración & dosificación , Metilprednisolona/análogos & derivados , Adolescente , Niño , Humanos , Metilprednisolona/administración & dosificación , Acetato de Metilprednisolona , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Simple bone cysts, also known as a unicameral bone cysts or solitary bone cysts, are the most common type of benign bone lesion in growing children. Cysts may lead to repeated pathological fracture (fracture that occurs in an area of bone weakened by a disease process). Occasionally, these fractures may result in symptomatic malunion. The main goals of treatment are to decrease the risk of pathological fracture, enhance cyst healing and resolve pain. Despite the numerous treatment methods that have been used for simple bone cysts in long bones of children, there is no consensus on the best procedure. OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating simple bone cysts in the long bones of children, including adolescents.We intended the following main comparisons: invasive (e.g. injections, curettage, surgical fixation) versus non-invasive interventions (e.g. observation, plaster cast, restricted activity); different categories of invasive interventions (i.e. injections, curettage, drilling holes and decompression, surgical fixation and continued decompression); different variations of each category of invasive intervention (e.g. different injection substances: autologous bone marrow versus steroid). SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (December 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, 2013 Issue 12), MEDLINE (1946 to 12 December 2013), EMBASE (1974 to 12 December 2013) and the China National Knowledge Infrastructure Platform (31 December 2013). We also searched trial registers, conference proceedings and reference lists. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials evaluating methods for treating simple bone cysts in the long bones of children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results and performed study selection. We resolved differences in opinion between review authors by discussion and by consulting a third review author. Two review authors independently assessed risk of bias and data extraction. We summarised data using risk ratios (RRs) or mean differences (MDs), as appropriate, and 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the overall quality of the evidence. MAIN RESULTS: The only included trial was a multicentre randomised controlled trial (RCT) conducted at 24 locations in North America and India that compared bone marrow injection with steroid (methylprednisolone acetate) injection for treating simple bone cysts. Up to three injections were planned for participants in each group. The trial involved 90 children (mean age 9.5 years) and presented results for 77 children at two-year follow-up. Although the trial had secure allocation concealment, it was at high risk of performance bias and from major imbalances in baseline characteristics. Reflecting these study limitations, we downgraded the quality of evidence by two levels to 'low' for most outcomes, meaning that we are unsure about the estimates of effect. For outcomes where there was serious imprecision, we downgraded the quality of evidence by a further level to 'very low'.The trial provided very low quality evidence that fewer children in the bone marrow injection group had radiographically assessed healing of bone cysts at two years than in the steroid injection group (9/39 versus 16/38; RR 0.55 favouring steroid injection, 95% CI 0.28 to 1.09). However, the result was uncertain and may be compatible with no difference or small benefit favouring bone marrow injection. Based on an illustrative success rate of 421 children with healed bone cysts per 1000 children treated with steroid injections, this equates to 189 fewer (95% CI 303 fewer to 38 more) children with healed bone cysts per 1000 children treated with bone marrow injections. There was low quality evidence of a lack of difference between the two interventions at two years in functional outcome, based on the Activity Scale for Kids function score (0 to 100; higher scores equate to better outcome: MD -0.90; 95% CI -4.26 to 2.46) or in pain assessed using the Oucher pain score. There was very low quality evidence of a lack of differences between the two interventions for adverse events: subsequent pathological fracture (9/39 versus 11/38; RR 0.80, 95% CI 0.37 to 1.70) or superficial infection (two cases in the bone marrow group). Recurrence of bone cyst, unacceptable malunion, return to normal activities, and participant satisfaction were not reported. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine the relative effects of bone marrow versus steroid injections, although the bone marrow injections are more invasive. Noteably, the rate of radiographically assessed healing of the bone cyst at two years was well under 50% for both interventions. Overall, there is a lack of evidence to determine the best method for treating simple bone cysts in the long bones of children. Further RCTs of sufficient size and quality are needed to guide clinical practice.
Asunto(s)
Quistes Óseos/tratamiento farmacológico , Trasplante de Médula Ósea/métodos , Glucocorticoides/administración & dosificación , Metilprednisolona/análogos & derivados , Adolescente , Niño , Humanos , Metilprednisolona/administración & dosificación , Acetato de Metilprednisolona , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Persistent pulmonary hypertension of the newborn (PPHN) is a common pulmonary vascular disease during the neonatal period, and it is associated with a high clinical mortality rate and a poor prognosis. At present, the treatment of PPHN is based mainly on inhaled nitric oxide (iNO), highfrequency ventilation, and pulmonary vasodilators. Sildenafil has gradually begun to be used in recent years for the treatment of PPHN and has exhibited some success; however, its detailed mechanism of action requires further elucidation. An animal model of neonatal pulmonary hypertension (neonatal rats, 48 h after birth, 10% O2, 14 days) as well as a cell model [human pulmonary artery smooth muscle cells (PASMCs), 4% O2, 60 h] were established. The effects of sildenafil on pulmonary hypertension in neonatal rats were evaluated by hematoxylin and eosin staining, immunofluorescence analysis, western blotting and PCR, and the changes in peroxisome proliferatoractivated receptor γ (PPARγ), transient receptor potential canonical (TRPC)1, TRPC6 and Ki67 expression levels were detected under hypoxic conditions. The results revealed that sildenafil reversed the increases in the right ventricular mean pressure and right ventricular hypertrophy index induced by hypoxia, and attenuated pulmonary arterial remodeling as well as PASMC proliferation. The inhibitory effects of sildenafil on TRPC expression and PASMC proliferation were attenuated by GW9662 and PPARγ small interfering RNA. In conclusion, sildenafil protects against hypoxiainduced pulmonary hypertension and right ventricular hypertrophy in neonatal rats by upregulating PPARγ expression and downregulating TRPC1 and TRPC6 expression.
Asunto(s)
Regulación hacia Abajo , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Hipoxia/complicaciones , PPAR gamma/metabolismo , Citrato de Sildenafil/uso terapéutico , Canales Catiónicos TRPC/metabolismo , Animales , Animales Recién Nacidos , Presión Sanguínea/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión Pulmonar/fisiopatología , Hipoxia/fisiopatología , Antígeno Ki-67/metabolismo , Masculino , Miocitos del Músculo Liso/metabolismo , Arteria Pulmonar/patología , Ratas Sprague-Dawley , Citrato de Sildenafil/farmacología , Regulación hacia Arriba/efectos de los fármacos , Remodelación Vascular/efectos de los fármacosRESUMEN
Background: Mycoplasma pneumoniae is a common pathogen of community-acquired pneumonia (CAP) in children. M. pneumoniae infection is usually regarded as a self-limiting disease, but in some special cases, it can also develop into refractory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study is to analyze the clinical characteristics of CRP (C-reactive protein), LDH (lactate dehydrogenase), ESR (erythrocyte sedimentation rate), D-dimer, neutrophils (%), lymphocytes (%), and lung consolidation in RMPP and explore their prediction results in the early stage of RMPP, which is important for early treatment. Methods: This systematic search was conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wangfang, and Cqvip, and the date was set until February 23, 2021. For the continuous variables, mean difference (MD) with 95% CI was adopted to evaluate CRP, LDH, ESR, D-dimer, neutrophils (%), lymphocytes (%), and the correlation between lung consolidation and RMPP. Results: 20 studies including 5289 patients were included in the analysis, and the results showed that the CRP of the RMPP group (MD (95% CI): 22.29 (12.20, 32.38), P < 0.001), LDH (MD (95% CI): 145.13 (78.62, 211.64), P < 0.001), neutrophils (%) (MD (95% CI): 7.27 (0.31, 14.23), P = 0.04), and D-dimer (MD (95% CI): 1.79 (-1.17, 4.74), P = 0.24) was higher than that of the NRMPP group; the risk of lung consolidation in the RMPP group (OR (95% CI): 14.29 (4.52, 45.12), P < 0.001) was higher than that in the NRMPP group, and there was no difference in ESR (MD (95% CI): 8.11 (-1.34, 17.56), P = 0.09) and lymphocytes (%) (MD (95% CI): -6.27 (-12.81, 0.27), P = 0.06) between the two groups. Conclusion: So, the available evidence indicates that CRP, LDH, neutrophils (%), D-dimer, and lung consolidation are predictive factors for RMPP.
Asunto(s)
Neumonía por Mycoplasma , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Niño , Humanos , L-Lactato Deshidrogenasa , Mycoplasma pneumoniae , Neumonía por Mycoplasma/diagnóstico , Neumonía por Mycoplasma/tratamiento farmacológicoRESUMEN
OBJECTIVE: To explore the possible mechanisms of lung necrosis by examining the effects of Streptoccus pneumoniae (S.p) on the ultrastructure of alveolar epithelial cells type â ¡(AEC-â ¡) in the lung tissues of mice and children. METHODS: The suspended solutions of S.p strains cultured from the blood of a child with pneumococcal necrotizing pneumonia (PNP) (0.3 mL, CFU: 1×108/L) were instilled into the trachea of pathogen-free mice to prepare PNP model. The same amount of normal saline was given for the control group (10 mice). The samples (1 mm3) from the lower lobe of right lung of the mice were obtained 92 hrs later and fixed in 2.5% glutaraldehyde. Normal and abnormal lung tissues (1 mm3) were obtained while operation for the left lower lobe pulmonary cavity excision in the child with PNP. The specimens were fixed in 2.5% glutaraldehyde and stored at 4â. A transmission electron microscope was employed for the examination of the ultrastructure of AEC-â ¡ in the lung tissues. RESULTS: Quantitative reduction and exfoliation of microvilli in S.p-infected AEC-â ¡ were observed in both mice and this child compared with the control. Enlarged size, enhanced evacuation and reduced density of the lamellar bodies were also presented. The number of mitochondria was obviously reduced. The nucleolus chromatin concentrated and showed an inhomogeneous distribution. CONCLUSIONS: S.p infection results in comparable damage to the ultrastructure of AEC-â ¡ in mice and children that may represent one of the primary causes responsible for S.p-induced lung tissue necrosis.
Asunto(s)
Neumonía Neumocócica/patología , Alveolos Pulmonares/ultraestructura , Animales , Niño , Células Epiteliales/ultraestructura , Femenino , Humanos , RatonesRESUMEN
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in premature infants, and alveolar dysplasia and pulmonary vascular development disorders are the predominant pathological features. Apoptosis of lung epithelial cells is a key factor in the pathological process of alveolar developmental arrest. Endoplasmic reticulum stress (ERS)associated apoptosis is a noncanonical apoptotic pathway involved in the development of several pulmonary diseases. Previous studies have demonstrated that protein kinase RNAlike endoplasmic reticulum kinase, inositolrequiring enzyme 1α (IRE1α) and activating transcription factor 6 can initiate the apoptosis signaling pathway mediated by ERS and induce apoptosis of injured cells. Among them, the IRE1α pathway is the most conservative pathway in the unfolded protein response, which serves an important role in a number of pathological environments, to the extent of determining cell fate; however, it is rarely reported in BPD. Based on the establishment of a rat BPD model, the present study verified the activation of ERS in BPD and further confirmed that prolonged ERS inhibited the protective pathway, IRE1α/Xbox binding proteins, and activated the proapoptotic pathway, IRE1α/cJun Nterminal kinase, to induce the apoptosis of lung epitheliums.
Asunto(s)
Displasia Broncopulmonar/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Hiperoxia/metabolismo , Complejos Multienzimáticos/genética , Complejos Multienzimáticos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Factor de Transcripción Activador 6/metabolismo , Animales , Apoptosis , Displasia Broncopulmonar/genética , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Fosforilación , Ratas , Respuesta de Proteína Desplegada , Proteína 1 de Unión a la X-Box/metabolismoRESUMEN
OBJECTIVE: The present study aimed to characterize the clinical presentations and magnetic resonance imaging including conventional MRI and diffusion-weighted imaging (DWI) in newborns with cerebral infarction. METHODS: Clinical records of 16 newborn infants with cerebral infarction were reviewed. All cases underwent DWI examination in addition to conventional MRI examination [T1-weighted (T1W) and T2-weighted (T2W)]within 5 days after birth. Five patients received the second MRI examination at the age of 11 to 18 days. RESULTS: Eight patients had antenatal risk factors, 9 had intranatal risk factors, and no postnatal risk factors were found. Seizures as the first symptom were noted in 11 neonates, with a short duration and a low frequency. The first imaging examination (within 5 days) showed a slight hypointensity on T1W, a slight hyperintensity on T2W and significantly increased signal intensity with a clear boundary on DWI in the lesions. In the MRI re-examination, more obvious hypointensity on T1W and hyperintensity on T2W were noted, while hypointensity was shown on DWI in the lesions compared with the first imaging results. CONCLUSIONS: Seizures characterized by short duration and low frequency usually may be the first symptom in newborns with cerebral infarction. A hyperintensity on DWI was shown in the lesions at the early stage of neonatal cerebral infarction. A hypointensity on T1W and a hyperintensity on T2W were demonstrated in the lesions with increasing disease duration.
Asunto(s)
Encéfalo/patología , Infarto Cerebral/diagnóstico , Imagen por Resonancia Magnética , Femenino , Humanos , Recién Nacido , Masculino , Tomografía Computarizada por Rayos XRESUMEN
The broad spectrum of disabilities caused by white matter injury (WMI) cannot be explained simply by hypomyelination. Synaptic injury in the thalamus may be related to disabilities in WMI survivors. Neuronal injury in the thalamus has been found most commonly in autopsy cases of preterm WMI. We hypothesized that hypoxia/ischemia (HI) in neonatal rats results in synaptic abnormalities in the thalamus that contribute to disabilities in WMI survivors. We examined changes in synapses in a neonatal rat model of HI-induced WMI. Right common carotid artery ligation and hypoxia (8% oxygen for 2.5 hours (h)) were performed in three-day-old Sprague-Dawley rats. We found HI rats performed worse in the Morris water maze test than sham rats, suggesting long-term cognition impairment after HI injury. A loss of synapses in the thalamus accompanied by hypomyelination and oligodendrocytes (OLs) reduction was observed. At the ultrastructural level, reductions in active zone (AZ) length and postsynaptic density (PSD) thickness were detected at 2 weeks after HI exposure. Furthermore, increased expression of synaptophysin and PSD-95 in both groups was observed from 3 days (d) to 21 d after hypoxic/ischemic (HI) injury. PSD-95 expression was significantly lower in HI rats than in sham rats from 14 d to 21 d after HI injury, and synaptophysin expression was significantly lower in HI rats from 7 d to 14 d after HI injury. However, no significant difference in synaptophysin expression was observed between HI rats and sham rats at 21 d after HI injury. The results demonstrated synaptic abnormalities in the thalamus accompanied by hypomyelination in WMI in response to HI exposure, which may contribute to the diverse neurological defects observed in WMI patients. Although synaptic reorganization occurred as a compensatory response to HI injury, the impairments in synaptic transmission were not reversed.
Asunto(s)
Lesiones Encefálicas/patología , Hipoxia-Isquemia Encefálica/patología , Hipoxia/patología , Sinapsis/patología , Tálamo/patología , Sustancia Blanca/patología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Aprendizaje por Laberinto/fisiología , Oligodendroglía/patología , Densidad Postsináptica/patología , Ratas , Ratas Sprague-Dawley , Transmisión Sináptica/fisiologíaRESUMEN
BACKGROUND: Bronchial asthma is affected by both environmental and genetic factors. The orosomucoid 1-like protein 3 (ORMDL3) gene is related to childhood asthma and is involved in airway inflammation and airway remodeling. The ORMDL3 promoter contains binding sites for the histone acetylase p300. Gene expression can be affected by epigenetic modifications. This study aimed to investigate whether the p300-mediated histone acetylation (HAT) of ORMDL3 gene affects airway inflammation and remodeling in asthma. METHODS: 16HBE14o- cells were transfected with various concentrations of a wild-type p300 plasmid or p300HAT-deletion plasmids. A dual luciferase reporter assay was used to examine the effect of p300-mediated HAT on the ORMDL3 promoter. Thirty BALB/c mice were randomly divided into a control group, an ovalbumin (OVA)-induced asthma group and an asthmaâ¯+â¯C646 (a selective inhibitor of p300) group. Noninvasive lung function tests were conducted to examine airway hyperreactivity (AHR) in the different groups. HE and Masson's trichrome staining was performed to examine airway remodeling and inflammation. Immunohistochemistry, western blotting and real-time PCR were used to analyze ORMDL3 expression in lung tissues. ELISA and western blotting were used to evaluate the HAT status in lung tissue. The ChIP assay was used to determine the relationship of the ORMDL3 promoter to p300 or acetylated histone H3 (aceH3). RESULTS: p300 activated transcription from the ORMDL3 promoter, resulting in an increase in endogenous ORMDL3 mRNA levels. ORMDL3 promoter activity was reduced when the HAT activity of p300 was lost. ORMDL3 expression was elevated, and HAT activity was high in the lung tissues of asthmatic mice. p300 and aceH3 bound to the promoter region of ORMDL3. In the asthma group, the amounts of p300 and aceH3 recruited to the ORMDL3 promoter were increased. C646 inhibited p300 expression and reduced HAT activity and aceH3 levels in asthmatic mice, thereby reducing ORMDL3 expression and relieving AHR and airway remodeling. CONCLUSION: p300-mediated HAT modulates the expression of the asthma susceptibility gene ORMDL3, thereby improving the process of airway inflammation and remodeling in asthma.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Asma/metabolismo , Proteína p300 Asociada a E1A/genética , Histonas/metabolismo , Proteínas de la Membrana/metabolismo , Acetilación , Animales , Asma/patología , Asma/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Femenino , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , TransfecciónRESUMEN
As research into periventricular leukomalacia (PVL) gradually increases, concerns are emerging about longterm neuron injury. The present study aimed to investigate neuronal injury and the relevant alterations in apoptosis and autophagy in a PVL model established previously. A rat model of hypoxiaischemiainduced PVL was established. In the model group, SpragueDawley (SD) rats [postnatal day 3 (P3)] were subjected to right common carotid artery ligation followed by suturing and exposed to 68% oxygen for 2 h; in the control group, SD rats (P3) were subjected to right common carotid artery dissection followed by suturing, without ligation and hypoxic exposure. At 1, 3, 7 and 14 days following modeling, brain tissue samples were collected and stained with hematoxylin and eosin. Cellular apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and the protein and mRNA expression alterations of neuronal nuclei (NeuN), caspase3 and Beclin 1 in the model group were detected by western blot analysis and reverse transcriptionquantitative polymerase chain reaction (RTqPCR) analyses. Compared with the control group, the protein and mRNA expression levels of NeuN (a marker of mature neurons) were markedly reduced, the number of positive cells was increased as detected by TUNEL, and the protein and mRNA expression levels of caspase3 and Beclin 1 were elevated in the model group. In the rat model of hypoxiaischemiainduced PVL, oligodendrocyte injury and myelinization disorders were observed, in addition to neuron injury, a decrease in mature neurons and the copresence of apoptosis and autophagy. However, apoptosis and autophagy exist in different phases: Apoptosis is involved in neuron injury, while autophagy is likely to have a protective role.
Asunto(s)
Apoptosis , Autofagia , Hipoxia-Isquemia Encefálica/complicaciones , Leucomalacia Periventricular/etiología , Leucomalacia Periventricular/metabolismo , Neuronas/metabolismo , Animales , Animales Recién Nacidos , Beclina-1/genética , Beclina-1/metabolismo , Biomarcadores , Biopsia , Caspasa 3/genética , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Inmunohistoquímica , Leucomalacia Periventricular/patología , Proteínas del Tejido Nervioso/metabolismo , Neuronas/patología , RatasRESUMEN
INTRODUCTION: As a common disease with a complex risk, including genetic and environmental factors, atopic asthma is prevalent but treatable. The aim of the study was to predict the underlying mechanism of asthma and identify target genes for the disease. METHODS: The affymetrix chip data, GSE18965, were available from Gene Expression Omnibus and the differentially expressed genes (DEGs) between nine atopic asthmatic specimens and seven healthy nonatopic samples were identified by R. Then Gene Ontology and pathway enrichment analyses were performed to these DEGs. Further, search tool for the retrieval of interacting genes/proteins (STRING) was used to select protein-protein interaction (PPI) for DEGs, and then the network was visualized by Cytoscape. Finally, transcription factor binding site analysis was conducted to the hot gene. RESULTS: Total 565 DEGs were identified, including 535 upregulated and 30 downregulated genes. The upregulated genes, such as structural maintenance of chromosome (SMC)3, significantly affected cellular component of extracellular matrix (P = 1.56E-04). Otherwise, DEGs were remarkably enriched in three pathways, including transforming growth factor-beta signaling pathway (P = 0.005252649). Further, SMC3 was detected as hot gene in PPI network, and NET (Elk3) was predicted as the significant transcription factor for this gene. CONCLUSION: SMC3 may play an important role in atopic asthma development; therefore, it has the potential to be the target for the disease. Moreover, our findings provide more knowledge about the mechanism of atopic asthma and help the researchers to explore it in future.
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Asma/genética , Proteínas de Ciclo Celular/genética , Proteoglicanos Tipo Condroitín Sulfato/genética , Proteínas Cromosómicas no Histona/genética , Adolescente , Asma/metabolismo , Proteínas de Ciclo Celular/metabolismo , Niño , Preescolar , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Mapas de Interacción de Proteínas , Adulto JovenRESUMEN
BACKGROUND: the present study aimed to describe the characteristics of articles that had the most citations in the field of digestive endoscopy. METHOD: articles included were obtained from the Web of Science database, which were selected and ranked according to the number of citations. The characteristics of the 100 most cited articles were then analyzed. RESULTS: the number of citations of the top 100 of 303,063 eligible papers ranged from 370 to 2,866. The most cited paper was a study of colorectal cancer prevention using colonoscopic polypectomy. The most common topics discussed by the top 100 papers included colonoscopy (n = 33) and upper gastrointestinal endoscopy (n = 23), with most of the papers focusing on diagnosis (n = 24) and treatment (n = 15). CONCLUSION: by identifying the most influential publications, the present study could serve as a guide toward further development in the area of digestive endoscopy
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Humanos , Periódicos como Asunto/estadística & datos numéricos , Endoscopía del Sistema Digestivo/estadística & datos numéricos , Investigación Biomédica/estadística & datos numéricos , BibliometríaRESUMEN
INTRODUCTION: Degenerative disc disease (DDD) is a major health problem worldwide. Both Modic lesions and Schmorl's nodes are considered to correlate with DDD such as low back pain. Modic lesions are the changes of degenerative vertebral endplate and adjacent bone marrow observed on magnetic resonance imaging and are divided into three types. Modic type III lesions are thought to represent extensive subchondral bone sclerosis within the bone marrow of adjacent endplate. The pathological performance of Schmorl's nodes is cystic lesions around indistinct sclerotic margins and beneath the cartilaginous endplate. Coincidently, there are many similarities between Modic type III lesions and Schmorl's nodes including pathological appearances, pathogenetic location and related diseases. HYPOTHESIS: We hypothesize that Modic type III lesions and Schmorl's nodes are the same pathological changes, and Modic type III lesions may be the quiescent or incipient pathology phrase of Schmorl's nodes. The clinical symptoms of DDD are also accompanied by emergence of these pathological changes. TESTING: A longitudinal study could be used to test this hypothesis. We could measure and analyze whether Modic type III lesions have increased in size or evolved into Schmorl's nodes as time goes on. SIGNIFICANCE: This hypothesis explains the possible pathologic process of Modic type III lesions and Schmorl's nodes. If the hypothesis were conformed, Modic type III lesions and Schmorl's nodes will be rediscovered, which provides the new basis for the clinical treatment of DDD. In additions, this hypothesis also has crucial significances for the classification of Modic lesions.