RESUMEN
Objective: To explore the status quo, differences and influencing factors of health concern among the elderly in urban and rural areas. Methods: The data of China Health and Retirement Tracking Survey (CHARLS) in 2018 were used to describe the health concerns of the elderly in urban and rural areas by selecting relevant indicators. The differences of health concerns of the elderly in urban and rural areas were compared from two aspects of social demographic characteristics and health status. Multivariate logistic regression model was used to analyze the factors affecting the health concern of the elderly in urban and rural areas. Results: A total of 7 758 urban and rural elderly were included, including 1 913 urban elderly and 5 845 rural elderly. Half (3 899, 50.3%) of the elderly are at the average level of health concern, and there is a difference between urban and rural elderly (χ2=186.61,P<0.05). The rural and urban elderly with different characteristics had different health concerns. The rural elderly with more than two diseases had higher health concerns (χ2=13.71, P=0.001), and different living types of urban elderly people have different health concerns (χ2=28.96, P<0.001). Regression analysis showed that the health concern of the elderly in urban and rural areas was affected by many factors, gender (OR=1.51, P<0.001), health status (OR=2.18, P<0.001), cognitive function impairment (OR=2.93, P<0.001), depression (OR=0.49, P<0.001) is the main factor affecting the difference of health attention of the elderly in urban and rural areas. Whether to receive pension was the influential factor of health concern of the rural elderly (OR=0.63, P<0.05); Disability was an influential factor in the health concern of the urban elderly (OR=2.11, P<0.05). Conclusion: There is much room to improve the health attention of the elderly in urban and rural areas. It is suggested to increase the economic security of the elderly in rural areas and pay special attention to the disabled elderly in urban areas, so as to further improve the health status of the elderly groups.
Asunto(s)
Envejecimiento , Disfunción Cognitiva , Humanos , Anciano , Jubilación , China , CogniciónRESUMEN
China is rich in antimony, boron, and vanadium mineral resources, which have been detected in environmental water bodies and drinking water. During the revision process of the "Standards for Drinking Water Quality (GB5749-2006)", research and evaluation are focused on three indicators: antimony, boron and vanadium. Vanadium is added and the limit value of boron is adjusted. This study reviews and discusses the technical contents related to the revision of the antimony, boron and vanadium, including the environmental presence levels, exposure status, health effects, and the revision of the standard limits of these three indicators. Suggestions are also made for the implementation of this standard.
Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Humanos , Antimonio , Boro/análisis , China , Vanadio , Contaminantes Químicos del Agua/análisisRESUMEN
The establishment of limit values for standards of drinking water quality is an important and complex process. This study systematically introduced the methodology of the establishment of standard limit values for drinking water quality and elaborated on the workflow of setting limit values of water quality indicators, principles and methods of selecting water quality indicators, derivation of safety reference values, and establishment of limit values. It also aimed to provide reference and support for the future revision of relevant standards.
Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Humanos , Abastecimiento de Agua , Estándares de Referencia , Calidad del Agua , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVE: To describe the distribution and trend of infantile epilepsy among infants under 36 months in Ningbo, Zhejiang Province. METHODS: Using the birth cohort design, we retrospectively collected the local born infants in Ningbo national health information platform from 2015 to 2019, and took the first visit of epilepsy in the electronic medical record of the platform as the new case. The incidence density and 95% confidence interval (CI) of epilepsy were estimated by Poisson distribution. RESULTS: From 2015 to 2019, a total of 294 900 children were born in Ningbo, with male accounting for 51.92%. The total person-years of observation were 595 300, while the median follow-up person-years was 2.31 [interquartile range (IQR): 1.90]. There were 575 new onset epilepsy patients during the whole observation period. The total number of visits was 2 599, with an average of 4.52. The total incidence density was 96.59/100 000 person-years (95%CI: 88.85-104.82). The median age of onset was 13 months (IQR: 15), 0-12 months old infants had the highest incidence density (102.18/100 000 person-years), 25-36 months old infants had the lowest incidence density (89.68/100 000 person-years), and the difference was not statistically significant (P>0.05). The incidence density of male was 97.58/100 000 person-years, female was 95.53/100 000 person-years, and the difference was not statistically significant (P>0.05). Fenghua was the highest (130.54/100 000 person-years, 95%CI: 94.47-175.83) and Ninghai was the lowest (66.44/100 000 person-years, 95%CI: 47.02-91. 19), with significant difference (P < 0.05). There was no significant difference in the incidence density in different birth years (P>0.05). There was significant difference in the incidence density between 0-12 months old infants in different calendar years (Ptrend < 0.05). In this age group, the incidence density was the lowest in 2015 (69.41/100 000 person-years, 95%CI: 41.79-108.39), and the highest in 2019 (225.61/100 000 person-years, 95%CI: 186.10-271.03). There was no significant difference in the incidence density between 13-24 and 25-36 months old infants in different calendar years (P>0.05). CONCLUSION: The incidence density of epilepsy in 0-36 months old infants in Ningbo City from 2015 to 2019 was low as a whole, and there was no difference in age group, gender, and year of birth. The incidence density of 0-12 months old infants increased with the year.
Asunto(s)
Epilepsia , Preescolar , Ciudades , Epilepsia/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
This paper summarizes the development trend and characteristics of public opinion on health protection and disinfection strategies in the COVID-19 epidemic. The experience and deficiency of the strategies are discussed from the perspective of public opinion, and suggestions on how health protection and disinfection can help prevent and control infectious diseases are also put forward: to strengthen health protection and disinfection in key places and units; to evaluate health protection and disinfection effects as well as the transmission mechanism of virus in the environment; to establish a professional health protection and disinfection emergency science popularization mechanism and information release channel; to speed up the formulation and revision of health protection and disinfection standards related to the epidemic.
Asunto(s)
COVID-19 , Desinfección , Humanos , Salud Pública , Opinión Pública , SARS-CoV-2RESUMEN
In this paper, the history and current situation of environmental health standardization in China are reviewed, and the experience and shortcomings in the process of environmental health standardization in China are analyzed, suggestions for the next step of environmental health standards are also put forward.
Asunto(s)
Salud Ambiental , China , Humanos , Estándares de ReferenciaRESUMEN
OBJECTIVE: To evaluate the change of cell surface CXC chemokine receptor 4 (CXCR4) expression of stem cells from apical papilla (SCAP) after the inhibition of endocytotic pathway, thus to provide experimental basis for the mechanism of SCAP migration. METHODS: The immunofluorescence analysis was conducted to examine the co-expression of CXCR4 and endocytotic compartments, including early endosomes, recycling endosomes and lysosomes in SCAP. Several Rab proteins were applied as markers of organelles in the endocytotic pathway, including Rab5 for early endosomes, Rab11A for recycling endosomes, and Lamp1 for lysosomes. The co-localization of CXCR4 with these endodontic compartments was further observed by proximity ligation assay (PLA). SCAP was treated with two kinds of endocytotic inhibitors, Blebbistatin and Dynasore, at a concentration of 80 µmol/L, respectively. The conditioning time was 1 hour. Flow cytometry was carried out to evaluate the proportion of SCAP that expressed CXCR4 on cell surface. The data were analysed by analysis of variance (ANOVA). RESULTS: The red staining of CXCR4 on immunofluorescence confocal microscopy predominantly overlapped with the green staining of Rab5 and Rab11A, and partly overlapped with Lamp1. It indicated that most CXCR4 molecules were located in early endosomes and recycling endosomes, and some were located in lysosomes. The PLA results revealed that the co-localizaiton of CXCR4 with endocytotic compartments could be observed in early endosomes, recycling endosomes and lysosomes. According to the results of flow cytometry, the proportion of SCAP that expressed CXCR4 on cell surface was as low as 0.13%±0.10%. After the inhibition of endocytosis by pretreating the cells with the following two inhibitors, Blebbistatin and Dynasore, the percentage of SCAP that positively expressed CXCR4 on cell surface was significantly increased to 13.34%±1.31% in Blebbistatin group and 4.03%±0.92% in Dynasore group (F=16.721, P<0.001). Moreover, the number of SCAP that expressed CXCR4 on cell surface in Blebbistatin group was significantly higher than that in Dynasore group (P<0.001). CONCLUSION: The inhibition of endocytotic pathway could increase the number of SCAP that expressed CXCR4 on cell surface, and provide potency for the migration of SCAP.
Asunto(s)
Endocitosis , Receptores CXCR4 , Endosomas , Lisosomas , Células MadreRESUMEN
Objective: To identify post-marketing active surveillance systems for vaccine safety around the world and understand their features and mechanisms, in order to provide guidance for vaccine administration activities in China. Methods: Following the steps of scoping review, literature about active surveillance system for vaccine safety and published by 30 June 2018 were identified by searching electronic databases, including PubMed, Scopus, and Cochrane Library. Grey literature were also sought by exploring relevant websites. Identified literature were screened according to eligibility criteria, and informative data from included literature were then charted. Framework Synthesis and Thematic Analysis were performed to integrate the charted data. Results: 97 pieces of literature were included for review, and 11 active surveillance systems for vaccine safety were identified, mostly located in developed countries. These systems were constructed by 3 types of organizations: administration departments, academic or research institutions, and health care providers. Their data sources included immunization registries, electronic medical records, claims data, case reports of adverse events following immunization electronic questionnaires, and epidemiologic study data. According to their operation procedures, these systems were grouped into 4 modes of active surveillance: Data Linkage, Investigator Network, Automatic Follow-up System, Studies Consortium. Conclusion: Practice of active surveillance for vaccine safety greatly varies across countries, with different conditions and advantages. It is suggested that developing countries should choose suitable mode of active surveillance considering their local situations.
Asunto(s)
Vigilancia de Productos Comercializados/métodos , Vacunas/efectos adversos , China , Países en Desarrollo , HumanosRESUMEN
The Health Environment Promotion Campaigns (HEPCs) focus on the major environmental health issues and relevant factors of concern among the general public, and promote the achievement of the national health goal. Based on the summary and analysis of the background, key indicators, specific actions in different domains of the HEPCs, this paper proposes suggestions for scientifically implementing HEPCs from five aspects, namely, formulating implementation plans, establishing pilot areas, building comprehensive service platforms, improving the health literacy of residents and strengthening the development of protection technologies and standards.
Asunto(s)
Alfabetización en Salud , Promoción de la Salud , HumanosRESUMEN
According to different epochs and development needs, a series of practices on environmental health and sanitary engineering were carried out, which played significant roles in promoting national economic and social developments and protecting the public health. This paper reviewed the main achievements in the past 70 years infields of patriotic health campaign, water sanitation and toilet improvement in rural areas, surveillance and investigation, health standard system, sanitary engineering equipment, stove improvement etc., and then proposed several prospects in the future.
Asunto(s)
Salud Ambiental , Población Rural , Ingeniería Sanitaria , Saneamiento , China , Salud Ambiental/normas , Salud Ambiental/tendencias , Humanos , Salud Pública/normas , Ingeniería Sanitaria/tendencias , Saneamiento/normas , Saneamiento/tendencias , Cuartos de Baño/normasRESUMEN
We investigated the clinical significance of RUNX3 gene expression in human pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of pancreatic cancer tissues and paracancerous tissues were collected. RUNX3 expression was detected by real-time PCR and immunohistochemistry. The relationships between clinicopathological findings and the expression of RUNX3 were analyzed. The relative quantification level of RUNX3 mRNA expression in human pancreatic carcinoma tissues and paracancerous tissues was 2.60 (0.42-12.82) and 1.02 (0.19-3.58), respectively (P < 0.05). The percentage of positive cells expressing RUNX3 protein in human pancreatic tissues and paracancerous tissues was 45.5 ± 26.2 and 6.9 ± 6.0%, respectively (P < 0.01). The high RUNX3 group (N = 9) with 45.5% or more of the cancer cells staining for RUNX3 and the low RUNX3 group (N = 21) with less than 45.5% cancer cells staining for RUNX3. Low expression of RUNX3 correlated significantly with an advanced TNM stage (χ(2) = 6.897, P = 0.045), lymph node metastasis (χ(2) = 4.739, P = 0.029) and neural invasion (χ(2) = 5.44, P = 0.020). On the other hand, no association could be found between RUNX3 expression and clinicopathological variables including age, gender, tumor location, tumor size, tumor differentiation or the serum concentration of CEA and CA199. The expression of RUNX3 in pancreatic cancer tissues was obviously higher than that in the paracancerous tissues. Low expression of RUNX3 may have an important role in aggressiveness, lymph node metastasis and neural invasion in pancreatic cancer. In pancreatic carcinoma tissues, low expression of RUNX3 may indicate a poor prognosis.
Asunto(s)
Adenocarcinoma/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/biosíntesis , Neoplasias Pancreáticas/genética , Pronóstico , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patologíaRESUMEN
Achieving transgene integration into preselected genomic sites is currently one of the central tasks in stem cell gene therapy. A strategy to mediate such targeted integration involves site-specific endonucleases. Two genomic sites within the MBS85 and chemokine (C-C motif) receptor 5 (CCR5) genes (AAVS1 and CCR5 zinc-finger nuclease (CCR5-ZFN) sites, respectively) have recently been suggested as potential target regions for integration as their disruption has no functional consequence. We hypothesized that efficient transgene integration maybe affected by DNA accessibility of endonucleases and therefore studied the transcriptional and chromatin status of the AAVS1 and CCR5 sites in eight human induced pluripotent stem (iPS) cell lines and pooled CD34+ hematopoietic stem cells (HSCs). Matrix chromatin immunoprecipitation (ChIP) assays demonstrated that the CCR5 site and surrounding regions possessed a predominantly closed chromatin configuration consistent with its transcriptional inactivity in these cell types. In contrast, the AAVS1 site was located within a transcriptionally active region and exhibited an open chromatin configuration in both iPS cells and HSCs. To show that the AAVS1 site is readily amendable to genome modification, we expressed Rep78, an AAV2-derived protein with AAVS1-specific endonuclease activity, in iPS cells after adenoviral gene transfer. We showed that Rep78 efficiently associated with the AAVS1 site and triggered genome modifications within this site. On the other hand, binding to and modification of the CCR5-ZFN site by a ZFN was relatively inefficient. Our data suggest a critical influence of chromatin structure on efficacy of site-specific endonucleases used for genome editing.
Asunto(s)
Cromatina/química , Marcación de Gen , Genoma Humano , Células Madre Hematopoyéticas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Transgenes , Antígenos CD34/genética , Antígenos CD34/metabolismo , Cromatina/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dependovirus/genética , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Sitios Genéticos , Vectores Genéticos , Células Madre Hematopoyéticas/química , Humanos , Células Madre Pluripotentes Inducidas/química , Proteína Fosfatasa 1/genética , Proteína Fosfatasa 1/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Transcripción Genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Dedos de Zinc/genéticaRESUMEN
Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.
Asunto(s)
Tétanos , Tos Ferina , Inteligencia Artificial , Data Warehousing , Humanos , Toxoide Tetánico , Tos Ferina/prevención & controlRESUMEN
OBJECTIVE: To identify the environmental factors affecting the geographical distribution of Rhipicephalus microplus in China, and to examine the impact of climate changes on the distribution of R. microplus in China. METHODS: The national and international publications pertaining to the geographical distribution of R. microplus in China were retrieved, and the geographical location was extracted. The suitable habitats of R. microplus and the dominant environmental factors affecting the distribution of suitable habitats of R. microplus were predicted in China based on the geographical data and environmental variables using the ArcGIS 10.7 software and the maximum entropy model. RESULTS: Among the main climatic factors affecting the geographical distribution of R. microplus in China, the factors contributing more than 10% to the suitable habitats of R. microplus mainly include the annual mean precipitation (38.2%), the average temperature of the coldest quarter (28.4%) and the precipitation of the driest month (14.2%). The current suitable habitats of R. microplus were mainly found in southern China, and the high-, medium- and low-suitable areas accounted for 8.6%, 13.1% and 10.5% of the total land area of China, respectively. The suitable habitats of R. microplus were predicted to increase by 399 800 km2 in China using the maximum entropy model under the RCP 4.5 emissions scenario in 2070, and the emerging suitable habitats were mainly distributed in Gansu Province, Ningxia Hui Autonomous Region, Qinghai Province, Hebei Province, Shaanxi Province, Liaoning Province, Inner Mongolia Autonomous Region, Shandong Province, Sichuan Province and Tibeten Autonomous Region. In addition, the suitable habitats of R. microplus were predicted to show an overall expansion towards northward from present to 2070. CONCLUSIONS: Climate changes affect the distribution of suitable habitats of R. microplus in China, and annual mean precipitation may be a key factor affecting the distribution of suitable habitats of R. microplus.
Asunto(s)
Cambio Climático , Rhipicephalus , Animales , China , Ecosistema , TemperaturaRESUMEN
OBJECTIVE: To evaluate the impact of environmental and climatic factors on the distribution of suitable habitats of Haemaphysalis longicornis, and to predict the potential distribution of H. longicornis under different climate patterns in China. METHODS: Data pertaining to the distribution of H. longicornis were retrieved from public literatures. The effects of 19 climatic factors (annual mean temperature, annual mean temperature difference between day and night, isothermality, standard deviation of seasonal variation of temperature, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest season, mean temperature of the driest season, mean temperature of the warmest season, mean temperature of the coldest season, annual mean precipitation, precipitation of the wettest month, precipitation of the driest month, coefficient of variance of precipitation, precipitation of the wettest season, precipitation of the driest season, precipitation of the warmest season and precipitation of the coldest season) and 4 environmental factors (elevation, slope, slope aspect and vegetation coverage) on the potential distribution of H. longicornis were assessed using the maximum entropy (MaxEnt) model based on the H. longicornis distribution data and climatic and environmental data, and the potential distribution of H. longicornis was predicted under the RCP 2.6 and 8.5 emissions scenarios. RESULTS: Among the environmental and climatic factors affecting the geographical distribution of H. longicornis in China, the factors contributing more than 10% to the distribution of H. longicornis mainly included the precipitation of the driest month (26.0%), annual mean temperature (11.2%), annual mean precipitation (10.0%) and elevation (24.2%). Under the current climate pattern, the high-, medium- and low-suitable habitats of H. longicornis are 1 231 900, 1 696 200 km2 and 1 854 400 km2 in China, respectively. The distribution of H. longicornis increased by 336 100 km2 and 367 300 km2 in 2050 and 2070 under the RCP 2.6 emissions scenario, and increased by 381 000 km2 and 358 000 km2 in 2050 and 2070 under the RCP 8.5 emissions scenario in China, respectively. CONCLUSIONS: Climatic and environmental factors, such as precipitation, temperature and elevation, greatly affect the distribution of H. longicornis in China, and the suitable habitats of H. longicornis may expand in China under different climate patterns in future.
Asunto(s)
Cambio Climático , Ecosistema , China , Clima , Predicción , TemperaturaRESUMEN
Monoclonal antibody (mAb) has been widely applied in the treatment of human diseases, especially in malignant tumours. However, most antibodies produced in mouse by hybridoma technology might induce severe human anti-mouse reactions. We had reported a murine mAb CAb-1 of therapeutic interest for its specifically binding to a cell surface glycoprotein of human colon cancer. Here, we attempted to generate a reconstituted human-mouse chimeric Fab (cFab) of CAb-1 in vitro to reduce its antigenicity and increase its capacity of penetration. First, the genes of heavy and light chain variable region (VH, VL) of CAb-1 were cloned. Then, the chimeric light chain (cL) and Fd (cFd) were constructed and expressed in Escherichia coli. Finally, the reconstituted cFab was obtained by gradient dialysis of the mixture of cFd and cL. SDS-PAGE and western blot analysis showed the reconstituted cFab with a recovery rate of 70.2% when the initial total concentration of cL and cFd proteins to be 100 microg/ml. The reconstituted cFab maintained the affinity and specificity to colon cancer cells compared with its parental antibody as determined by immunostaining analysis, FACS and ELISA. Our results established a foundation for further application of the cFab in diagnosis and treatment of colon cancer.
Asunto(s)
Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/inmunología , Neoplasias del Colon/inmunología , Fragmentos Fab de Inmunoglobulinas/genética , Fragmentos Fab de Inmunoglobulinas/inmunología , Animales , Especificidad de Anticuerpos , Western Blotting , Quimera , Clonación Molecular , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Genes Sintéticos , Vectores Genéticos , Humanos , Hibridomas , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: This study aims to explore whether homeobox A11 antisense RNA (HOXA11-AS) could regulate inflammation induced by diabetic arteriosclerosis (DAA) via PI3K/AKT pathway. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect expressions of HOXA11-AS and proinflammatory genes in carotid endarterectomy samples of symptomatic and asymptomatic atherosclerosis (AS) patients, diabetes mellitus (DM), and non-DM patients. The above-mentioned genes in DM animal model and non-DM animal model were also detected. We detected the expression of HOXA11-AS in vascular smooth muscle cells (VSMCs) treated with platelet-derived growth factor (PDGF) or PDGF inhibitor imatinib, respectively. Subsequently, we applied cell transfection technology to interfere with the expression of HOXA11-AS in VSMCs. In vascular endothelial cells (VECs) and VSMCs, we detected the effect of HOXA11-AS on the expressions of genes related to the proliferation, migration, and cell cycle. Then, VSMCs were treated with tumor necrosis factor-α (TNF-α), and the expression of HOXA11-AS was examined in VSMCs. The effect of HOXA11-AS on TNF-α-induced inflammation in VSMCs was detected as well. Finally, we analyzed the effect of HOXA11-AS on PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs. RESULTS: HOXA11-AS expression was markedly increased in carotid endarterectomy specimens of symptomatic AS patients compared to that of asymptomatic AS patients. Expression levels of HOXA11-AS and pro-inflammatory genes were significantly elevated in carotid endarterectomy specimens of DM patients. Similarly, HOXA11-AS expression was also significantly increased in carotid arteries of DM mice compared with that of non-DM mice. PDGF could upregulate HOXA11-AS expression in VSMCs, which was reversed by PDGF inhibitor imatinib. HOXA11-AS knockdown could reduce the expressions of the proliferation-associated gene (PCNA) and the cycle-related genes (p21, p53), and also inhibited the proliferation and migration of VSMCs induced by PDGF. HOXA11-AS was upregulated by TNF-α. HOXA11-AS knockdown remarkably downregulated expressions of inflammation-related genes in VSMCs induced by TNF-α. In VECs, low expression of HOXA11-AS can inhibit the expression of TNF-α-induced pro-inflammatory genes and PDGF-induced vascular inflammation-related genes. Low expression of HOXA11-AS inhibited PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs. CONCLUSIONS: HOXA11-AS may participate in DAA by activating the PI3K/AKT pathway to regulate inflammation in VSMCs and VECs.
Asunto(s)
Arteriosclerosis/genética , Angiopatías Diabéticas/etiología , Proteínas de Homeodominio/genética , Animales , Ciclo Celular/genética , Proliferación Celular/genética , Células Cultivadas , Regulación hacia Abajo , Células Endoteliales/metabolismo , Humanos , Inflamación/metabolismo , Ratones , Miocitos del Músculo Liso/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/administración & dosificación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genética , Regulación hacia ArribaRESUMEN
OBJECTIVE: Rat models of hypobaric hypoxia-induced pulmonary hypertension are commonly used in studies of chronic mountain sickness, while there are few researches specially focusing on these rats model. This study aims to exploring possible pathogenesis of hypobaric hypoxia-induced pulmonary hypertension by experimenting on hypobaric hypoxia-induced PH rat models at different simulate- altitudes. MATERIALS AND METHODS: 32 healthy male SD rats were randomly divided into six groups of different degree and time period of hypobaric hypoxia. The mean pulmonary arterial pressure (m PAP), right ventricular pressure (RVSP), the right ventricle (RV), left ventricular (LV), ventricular septal (S), the right ventricular hypertrophy index (RVHI) [calculated under the formula of RV / (LV + S)], hematoxylin-eosin staining, elastic fibers staining, the ratio of the thickness of vascular wall to its outer diameter (MT%), the ratio of the cross-sectional area of the middle vascular wall to the total vascular cross-sectional area (MA%); the α-SMA, and the Ki6 expressions were detected to evaluated the pulmonary hypertension. RESULTS: There were significant differences of the mPAP, RVSP and RVHI value between the hypobaric hypoxia groups and the control group (p < 0.05). The mPAP, RVSP, RVHI, MT%, MA%, α-SMA, and Ki6 of rats in model groups at an altitude of 3KM were higher than those of the control group, which raised gradually with the number of weeks increasing. The mPAP, RVSP, RV / (LV + S) value, MT%, MA%, α-SMA, and Ki67 of the 5KM-4W group were significantly higher than those of the control group (p < 0.05). CONCLUSIONS: Rat models with pulmonary hypertension at different altitudes have been successfully established by automatic adjusting hypobaric hypoxia chamber. Exposure to a low oxygen environment at a simulate-altitude of 3 km for 8 weeks have caused the pathological remodeling of pulmonary vascular walls and pulmonary hypertension, and further led to a series of pathological changes, including right ventricular hypertrophy. This model is easy to be replicated with good reproducibility and provides evidence for clinical trial of drugs.
Asunto(s)
Mal de Altura/complicaciones , Hipoxia de la Célula/fisiología , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Mal de Altura/fisiopatología , Animales , Modelos Animales de Enfermedad , Hipoxia/fisiopatología , Pulmón/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Our previous work showed that ouabain increases retinal adhesion to the retinal pigment epithelium, but the mechanism of this effect has been unclear. In this study, we have found that the ouabain-induced increase in retinal adhesiveness was blocked reversibly by removing sodium from the medium or by exposure to hyperosmotic solution. Hyposmotic solution slowed down the postmortem failure of adhesion. Tissue edema could not be documented histologically, but retinal tissue water content increased by 2.9% after exposure to ouabain. These data suggest that the ouabain effect involves cellular edema, which may enhance adhesion by tightening the interdigitation between photoreceptor outer segments and retinal pigment epithelial microvilli.
Asunto(s)
Edema/etiología , Ouabaína/farmacología , Retina/efectos de los fármacos , Adhesividad , Animales , Concentración Osmolar , Epitelio Pigmentado Ocular/metabolismo , Conejos , Sodio/metabolismo , Factores de TiempoRESUMEN
The role of interphotoreceptor matrix (IPM) constituents in mediating adhesion between the retina and retinal pigment epithelium (RPE) was investigated by injecting specific enzymes into rabbit eyes either intravitreally or subretinally. Retinal adhesiveness was measured by peeling the retina from the pigment epithelium 1-3 days later and observing the amount of adherent pigment. Effects of enzymes on the IPM were monitored by observation of peanut agglutinin (PNA) binding to cone matrix sheaths; retinal and RPE toxicity was excluded by electroretinography and histology. Three enzymes that degrade glycosaminoglycans or saccharides known to be constituents of the IPM (chondroitinase ABC, neuraminidase, and testicular hyaluronidase) both weakened adhesion and altered PNA binding, although the effects on the cone matrix sheaths were different for each enzyme. An enzyme specific for hyaluronic acid (Streptomyces-derived hyaluronidase), which has not been identified as a major IPM constituent, had no effect on either adhesion or PNA binding. The authors conclude that IPM-associated glycoconjugates participate in retinal adhesion, although their precise composition, interaction with IPM components, and relationship to other mechanisms of adhesion remain to be determined.