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El objetivo fue conocer el vínculo entre la vivienda, la salud y la calidad de vida en un contexto de regeneración de viviendas sociales, a partir de las experiencias y percepciones de sus habitantes, indagando en aquellos mecanismos que sostienen este vínculo antes de la regeneración, y en aquellos elementos derivados de la regeneración de la vivienda que se materializan en mejoras en la calidad de vida y potencialmente en la salud. Entre 1980 y los 2000, Chile enfrentó un masivo déficit cuantitativo de vivienda mediante una política que entregó más de 120.000 departamentos de vivienda social de bajo costo. Hoy en día, miles presentan severos problemas de habitabilidad, generando consecuencias negativas para sus habitantes, su salud y bienestar. Buscando dar solución al deterioro de la vivienda y el espacio público, el Ministerio de Vivienda y Urbanismo desarrolló el Programa de Regeneración de Conjuntos Habitacionales. El proyecto RUCAS busca evaluar los efectos del programa en la salud y evidenciar el impacto de intervenciones como éstas en poblaciones vulnerables en Latinoamérica. Se presentan resultados de 8 entrevistas y 2 grupos focales realizados en un conjunto de vivienda social en proceso de intervención en Viña del Mar. Usando análisis de contenido discursivo, los resultados muestran que la mala calidad material de la vivienda se percibe como dañino para la salud. La vivienda regenerada en tanto, promueve la recuperación y re-apropiación de los espacios y sus usos, la sociabilidad, nuevas prácticas saludables, sentimientos positivos y bienestar psicológico, emergiendo el componente psicosocial de la relación de las personas con su vivienda. Se concluye que la regeneración de la vivienda tiene el potencial de beneficiar a la salud física y mental por mecanismos tanto directos, devenidos de la materialidad renovada, como indirectos relacionados con las prácticas y experiencias en el espacio habitado.
The objective was to understand the link between housing, health and quality of life in a context of social housing regeneration, through the experiences and perceptions of its inhabitants, exploring the mechanisms that sustain this link before regeneration, and those elements derived from housing regeneration that result in improvements in quality of life and potentially in health. Between 1980 and the 2000s, Chile faced a massive quantitative housing deficit through a policy that delivered more than 120,000 low-cost social housing apartments. Today, thousands present severe habitability problems, generating negative consequences for their inhabitants, their health and well-being. Seeking to solve the deterioration of housing and neighborhoods, the Chilean Ministry of Housing and Urbanism developed the Housing Complex Regeneration Program. The RUCAS project seeks to evaluate the effects of the program on health and to assess the impact of interventions such as these on vulnerable populations in Latin America. We present results of 8 interviews and 2 focus groups conducted in a social housing complex in process of intervention in Viña del Mar. Using discursive content analysis, results show that the poor material quality of housing is perceived as harmful to health. Regenerated housing, on the other hand, promotes the recovery and re-appropriation of spaces and their uses, sociability, new healthy practices, positive feelings and psychological well-being, bringing to the fore the psychosocial component of people's relationship with their house. It is concluded that housing regeneration has the potential to benefit physical and mental health through both direct mechanisms, derived from the renovated materiality, and indirect mechanisms related to the practices and experiences of the lived space.
O objetivo foi compreender a relação entre habitação, saúde e qualidade de vida em um contexto de regeneração da habitação social, com base nas experiências e percepções de seus habitantes, investigando aqueles mecanismos que sustentam esta relação antes da regeneração, e aqueles elementos derivados da regeneração que se materializam em melhorias na qualidade de vida e potencialmente na saúde. Entre 1980 e os anos 2000, o Chile enfrentou um enorme déficit habitacional quantitativo através de uma política que proporcionou mais de 120.000 moradias sociais de baixo custo. Hoje, milhares apresentam graves problemas de habitabilidade, gerando consequências negativas para seus habitantes, sua saúde e bem-estar. Em busca de uma solução para a deterioração da habitação e seus bairros, o Ministério da Habitação e Urbanismo do Chile desenvolveu o Programa de Regeneração Habitacional. O projeto RUCAS procura avaliar os efeitos do programa sobre a saúde e o impacto de tais intervenções sobre populações vulneráveis na América Latina. São apresentados os resultados de 8 entrevistas e 2 grupos focais realizados em um complexo habitacional social no processo de intervenção em Viña del Mar. Usando análise discursiva de conteúdo, os resultados mostram que a má qualidade do material da habitação é percebida como prejudicial à saúde. A moradia regenerada, por outro lado, promove a recuperação e reapropriação dos espaços e seus usos, a sociabilidade, novas práticas saudáveis, sentimentos positivos e bem-estar psicológico, emergindo o componente psicossocial da relação das pessoas com sua moradia. Conclui-se que a regeneração habitacional tem o potencial de beneficiar a saúde física e mental tanto através de mecanismos diretos, decorrentes da materialidade renovada, como de mecanismos indiretos relacionados às práticas e experiências no espaço vivido.
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ABSTRACT OBJECTIVES To explore the perceptions of residents regarding their health and well-being in areas of personal and collective life, in relation to the experience of urban transformation originated by the Program for the Recovery of Neighborhoods in Chile "Quiero mi Barrio" (PQMB). METHODS Qualitative study conducted in eight neighborhoods, which were subject to interventions between 2012-2015, located in seven communes of Chile: Arica, Renca, Padre Las Casas, Villarrica, Castro, Ancud. Eighteen focus groups and 27 interviews were conducted between 2018 and 2019. A content analysis was carried out following the social determinants of health approach. RESULTS Material conditions of neighborhood infrastructure and psychosocial determinants were the main emerging and predominant categories in the residents' narratives. The new or improved infrastructure enhances sports and playing practices, as well as contributes to the feeling of safety and to the improvement of walkable spaces, support networks, socialization and dynamization of social organization. However, neglected aspects were visualized. The program had limitations of structural character that operate locally, such as aging, individual lifestyles that limit participation, and contexts of insecurity, especially in neighborhoods victims of drug trafficking. CONCLUSIONS The urban changes originated by the PQMB included improvements in neighborhood infrastructure and in the psychosocial environment, which are perceived by residents as beneficial aspects and promoters of collective wellbeing. However, global phenomena, and those related to the program, limit its scope and have repercussions on the perception of overall wellbeing of the residents in the neighborhoods. To go deeper into how this or other state neighborhood programs may or may not favor equitable access of different social groups, or which works may be better used by the groups, is an aspect that enhances the integral action with other sectors and local actors in the territories.
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Humans , Male , Female , Urban Renewal , Chile , Community Participation , Qualitative Research , Social Determinants of Health , Neighborhood CharacteristicsABSTRACT
OBJECTIVE@#To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression.@*METHODS@#Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (n=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting.@*RESULTS@#The diabetic rats with depression showed significantly increased levels of blood glucose and leptin (P < 0.01) and prolonged immobility time in forced swimming test (P < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test (P < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased (P < 0.01) while hippocampal Gli-3 expression was increased significantly (P < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose (P < 0.01) and leptin level (P < 0.05) and improved their performance in behavioral tests (P < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus (P < 0.01) and reduced hippocampal expression of Gli-3 (P < 0.05) in the rat models.@*CONCLUSION@#ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.
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Animals , Rats , Blood Glucose , Bromodeoxyuridine , Cell Self Renewal , Cyclin D1 , Dentate Gyrus , Depression , Diabetes Mellitus, Experimental , Hippocampus , Leptin , Nestin , Rats, Sprague-DawleyABSTRACT
Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.
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Humans , Glioblastoma/genetics , Bromodeoxyuridine/therapeutic use , Signal Transduction , Proto-Oncogene Proteins c-myc/metabolism , Agar , Cell Proliferation , Cell Line, Tumor , Apoptosis , Jumonji Domain-Containing Histone Demethylases/metabolismABSTRACT
Aim To investigate the effect of m6A demethylase FTO inhibitor(FB23-2)on human glioblastoma stem cell activity. Methods The effects of FB23-2 and Temozolomide on GSC were detected by CCK-8 assay and neurosphere formation assay. The effect of FB23-2 on self-renewal of GSC was detected by limited dilution assay in vitro. The effect of FB23-2 on the proliferation of GSC was detected by EdU method. The effect of FB23-2 on apoptosis of glioblastoma stem cells was detected by flow cytometry. Results CCK-8 assay showed that FB23-2 could effectively inhibit the cell viability of GSC with IC50 values of 7.11 μmol·L-1 and 4.63 μmol·L-1,respectively. The size and number of GSC neural sphere in FB23-2 treatment group were significantly reduced compared with control group. In vitro limited dilution experiment showed that FB23-2 effectively inhibited the self-renewal ability of GSC. EdU incorporation experiment showed that compared with the control group,the treatment group decreased to(70.59±13.74)% and(50.33±4.53)%,respectively. The apoptotic rates of the treated group were(12.16±1.90)% and(16.77±1.17)% by flow cytometry. Conclusions FTO inhibitor FB23-2 can effectively inhibit GSC growth,self-renewal and the formation of neural sphere. In addition,FB23-2 can inhibit the proliferation of GSC and induce its apoptosis.
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Introduction: National Health Insurance Scheme (NHIS) was implemented in Ghana in 2004 to serve as the lifeline to realizing Universal Health Coverage (UHC). Available evidence suggests that, formal sector workers do not promptly renew their expired NHIS membership cards. This study was therefore conducted to unearth factors responsible for the failure of healthcare workers in the Kintampo North Municipality to promptly renew their health insurance membership whenever it expires. Methods: a descriptive cross-sectional design was used to conduct this study, where three hundred and ninety-seven (397) participants were recruited using a proportionate stratified sampling technique. All variables with a p-value <0.25 at the bivariate analysis level were selected and put into multiple logistic regression analysis models for statistical significance (p-value < 0.05). Odds ratios with their corresponding 95% Confidence Interval were reported. A p-value < 0.05 was set as level of significance. Results: almost all the respondents (94.0%) had NHIS membership cards; out of which 70.7% had valid membership cards. Fourty percent did not renew their expired NHIS membership cards for more than 7 months. From the study, reasons given for health workers´ inability to promptly renew NHIS membership included: 212 (19.8%) indicated forgetfulness, busy schedules 191 (17.9%), procrastination 167 (15.6%), self-medication 170 (15.9%) and utilization of spiritual homes (4.5%). All socio-economic factors were significantly associated at the bivariate level (p<0.05). However, in the multiple logistic regression model, employment status, the type of health staff and monthly salary lost their statistical significance. Conclusion: NHIS subscription and membership renewals are high among healthcare workers who participated in the study in Kintampo North District of the Bono East Region of Ghana. However, there is the need to encourage those who do not renew their expired cards by NHIA and its accredited facilities sensitizing the general populace on the utilization of mobile phones to renew NHIS membership cards in order to prevent long waiting time and bureaucracies in renewing NHIS cards. It will be prudent for NHIS to liaise with Government of Ghana (GoG) to put measures in place to facilitate automatic membership renewals for public sector workers who for some other reasons often fail to renew their cards.
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Humans , Male , Female , Delivery of Health Care , Universal Health Coverage , National Health Programs , Confidence Intervals , Health Personnel , Health Smart CardsABSTRACT
BACKGROUND: Bladder cancer stem cells could promote the recurrence and drug resistance of bladder cancer. Numerous studies have shown that keratin 6B (KRT6B) is involved in the production and progression of tumors, and is closely related to the prognosis of tumors. OBJECTIVE: To observe the expression of keratin 6B in CD44+ bladder cancer stem cells and to show the influence of keratin 6B on proliferation, migration, and self-renewal of bladder cancer stem cells, and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients. METHODS: (1) CD44+ 5637 bladder cancer stem cells were isolated by magnetic active cell sorting. Cancer stem cell-related gene expression of SOX2, OCT4, and NANOG was detected via real-time polymerase chain reaction. The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44+ cells. Keratin 6B expression was detected in CD44+ bladder cancer stem cells by real-time polymerase chain reaction. (2) The CD44+5637 bladder cancer stem cells were divided into two groups. In the keratin 6B siRNA group, keratin 6B small interfering RNA was transfected into CD44+ bladder cancer stem cells. Untransfected CD44+ bladder cancer stem cells were used as the black control group. Cells were collected at 2 days post-transfection. The proliferation, migration, and self-renewal capacity of keratin 6B siRNA CD44+ bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively. (3) Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B. (4) ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer. RESULTS AND CONCLUSION: (1) Cancer stem cell-related genes (SOX2, OCT4, NANOG) and keratin 6B expression was higher in CD44+ cells isolated by magnetic active cell sorting compared with CD44- cells (P < 0.05). Cell proliferation, migration, and in vitro spheroid formation were significantly increased (P < 0.05). Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44+ bladder cancer stem cells (P < 0.05). (2) Compared with the blank control group, the proliferation and migration of CD44+ bladder cancer stem cells after transfection of keratin 6B small interfering RNA (P < 0.05), and the number of tumorsphere significantly diminished (P < 0.05); the expression of Notch1 and Hes1 mRNA increased (P < 0.05). (3) Keratin 6B and CD44v6 were significantly different in bladder cancer tissue (P=0.006). The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B. (4) The results showed that keratin 6B was highly expressed in CD44+ bladder cancer stem cells, and could promote the proliferation, migration, and self-renewal capacity of bladder cancer stem cells. The high expression of keratin 6B contributes to improving the survival of bladder cancer patients.
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Resumen La política internacional de protección del patrimonio mundial de la UNESCO se integró en las agendas de desarrollo nacional y local de los países de América Latina, gestionando proyectos de mejoramiento social y urbano en barrios históricos de las ciudades. Los efectos sociales, ambientales y económicos de estos procesos de patrimonialización de los lugares no han sido suficientemente analizados. En este sentido, y asumiendo una perspectiva psicoambiental, esta investigación describe y compara los índices de Apego al Lugar e Identidad de Lugar en habitantes de tres barrios de la ciudad de Valparaíso (n=544) (Chile) y dos en la ciudad de Quito (n=209) (Ecuador), que se encuentran ubicados en zonas catalogadas como Patrimonio de la Humanidad. A través de la aplicación de pruebas t de Student de comparación de medias y d de Cohen de valoración del tamaño del efecto, se observó que las personas que cuentan con mayor tiempo de residencia, que habitan barrios patrimoniales consolidados (donde las dimensiones socio-urbanas del entorno se encuentran mayormente intervenidas y desarrolladas) y que son propietarias de sus viviendas presentan puntajes más altos de Apego al Lugar e Identidad de Lugar. Se observó un nivel moderado de Apego de Lugar e Identidad de Lugar en los habitantes de los barrios patrimoniales de las ciudades de Valparaíso y Quito.
Abstract UNESCO's international policy for the protection of world heritage was integrated into the national and local development agendas of Latin American countries, managing social and urban improvement projects in historic city districts. The social, environmental and economic effects of these processes of heritage sites have not been sufficiently analyzed. In this sense and assuming a psycho-environmental perspective, this research describes and compares the indices of place attachment and place identity in 3 neighborhoods in the city of Valparaiso (n=544) and 2 in the city of Quito (n=209), which are located in areas classified as World Heritage. Through the application of Student t tests for comparing means and Cohen d tests for assessing the size of the effect, it was observed that people who have resided for longer periods of time, who live in consolidated heritage neighborhoods and who own their own homes, show higher scores in terms of place attachment and place identity. A moderate level of Place Attachment and Place Identity was observed in Valparaíso and Quito.
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RESUMEN: El presente artículo tiene por objeto aportar a la discusión y reflexión de los elementos teóricos-conceptuales que debe incorporar un proceso de renovación curricular, en este caso de la carrera de odontología de la Universidad de La Frontera, Chile. Este proceso debe orientarse hacia los nuevos contextos laborales que requiere hoy en día la odontología; estableciendo diseños y lineamientos claros para el desarrollo de los aprendizajes significativosde los estudiantes -con herramientas específicas, saberes interdisciplinarios y competenciastécnicas para la formación integral del profesional-y que a su v ez logre incorporar en todas sus etapas no tan a los estudiantes sino que también a su cuerpo docente. A fin que se logre una apropiación significativa entre todos los actores que participan, adquiriendo un compromiso y alineación con este desafío educativo-formativo, cuyo propósito es la mejora sustancial en la formación profesional odontológica en la región de La Araucanía, Chile.
ABSTRACT: The objective of this article is to contribute to the discussion and reflection of the theoretical- conceptual elements that should be incorporated in a process of curricular renewal. In this case, concerning the dental degree of the Universidad de La Frontera, Chile, this process should be geared toward the new work context required in the dental field nowadays. Clear designs and guidelines for the development of students' meaningful learning should be established. These should include Interdisciplinary knowledge, technical competences and specific educational tools in a comprehensive educational model for the students and subsequent professionals. Faculty as well as students ought to be included in all stages of this process. To accomplish this challenge in education and training requires a significant and absolute commitment on the part of all players involved, given that the objective is the substantial improvement of the dental professional education in the La Araucanía region.
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Resumo O reaparecimento de variabilidade comportamental previamente extinta (i.e., recaída) foi investigado por meio dos modelos experimentais de renovação, restabelecimento e ressurgência. Na Fase de Treino (contexto A), ao serem expostos ao esquema múltiplo Lag 10 Acoplado, ratos apresentaram níveis similares de variabilidade nos dois componentes. Na Fase de Eliminação (contexto B), o esquema múltiplo Repetição Repetição promoveu a extinção da variabilidade. Na Fase de Teste (contexto A), com a suspensão da contingência de repetição e a liberação de reforços independentes, a variabilidade reapareceu no componente "Lag 10", anteriormente correlacionado com reforçamento da variação, mas não no componente "Acoplado". Esse resultado sugere que a variabilidade observada no teste de recaída corresponde à variabilidade operante, e não à variabilidade induzida pela extinção.
Abstract The reappearance of previously extinguished behavioral variability (i.e. relapse) was investigated with three experimental models: renewal, reinstatement and resurgence. In the Training Phase (context A), when exposed to the multiple Lag 10 Yoke schedule, rats showed similar levels of variability in both components. In the Elimination Phase (context B), the multiple Repetition schedule promoted the extinction of variability. In the Test Phase (context A), with the suspension of the repetition contingency and the delivery of response-independent reinforcers, variability reappeared in the "Lag 10" component, the one previously correlated with the reinforcement of variation, but not in the "Yoke" component. This result suggests that the variability observed in the relapse test corresponded to operant variability, and not to extinction-induced variability.
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Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.
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The lineage transition between epithelium and mesenchyme is a process known as epithelial- mesenchymal transition (EMT) , by which polarized epithelial cells lose their adhesion property and obtain mesenchymal cell phenotypes.EMT is commonly found in embryonic development, wound healing, organ fibrosis and tumor metastasis.EMT and mesenchymal-epithelial transition (MET) are involved in the early and late development of embryo, such as implantation, gastrulation, heart development and so on.EMT and MET are involved in the regulation of stem cell phenotype changes and cell migration, which are important mechanisms of cell differentiation and three-dimensional tissue construction.The expression of cell adhesion molecules is transformed from E-cadherin to N-cadherin, which is an important sign of EMT.By interacting with (3-catenin, p 120-catenin and a-catenin, E-cadherin can affect the activation of Wnt, small GTPase superfamily and other signaling pathways and regulate cytoskeleton movement.TGF, Notch, Wnt, BMP, FGF, and other signaling pathways, Snail, Twist, Zeb and other transcription factors, together with epigenetic modifying enzymes, participate in the initiation and regulation of EMT in a coordinated way.In vitro models showed that E-cadherin was involved in self-renewal of stem cells.Somatic cell reprogramming could he regarded as MET, and the expression of E- cadherin can he obtained in somatic cells after transfection of reprogramming factors.In vitro studies have found that EMT and its related molecules (such as E-eadherin, Snail, Twist, Zeb, etc.) were involved in the early triploblast differentiation and the formation of specific cell types in the late stage.The study on the mechanism of EMT will help to improve the differentiation efficiency of stem cells in vitro and promote the induction of organoids.
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RESUMO Este trabalho investiga a renovação das águas no Complexo Estuarino de Paranaguá (CEP), localizado no estado do Paraná, Brasil, usando o sistema de modelagem computacional SisBaHiA®. Um modelo de circulação hidrodinâmica, para a definição dos padrões de circulação, e um modelo de transporte Euleriano, para calcular a taxa de renovação (TR), idade da água (IA) e escoamento residual, foram implementados. A TR, a IA e o escoamento residual foram determinados para diferentes cenários hidrodinâmicos, com períodos representativos de verão e de inverno e, consequentemente, com diferentes forçantes (maré, vazão ou vento) com o objetivo de identificar as possíveis áreas de estagnação. Os resultados obtidos mostram que a maré e as vazões fluviais são os forçantes de maior importância na renovação das águas do CEP. Em todos os cenários foram identificadas duas possíveis áreas de estagnação, que apresentam menores TRs e maior IA, quando comparadas com outras regiões, a saber, a região da baía dos Pinheiros e a região próxima à cidade de Paranaguá. Durante o verão e considerando todos os forçantes, as TRs na região da baía dos Pinheiros e na região próxima à cidade de Paranaguá são menores que 95%, enquanto nas demais regiões do CEP os valores são superiores a 95%.
ABSTRACT This work investigates the water renewal in the Paranaguá Estuarine Complex (PEC), located in the state of Paraná, Brazil, using the SisBaHiA® computer modelling system. A hydrodynamic circulation model, for the definition of hydrodynamic circulation patterns, and an Eulerian transport model, for the computation of the water renewal rate, water age and residual circulation, were implemented. The water renewal rate, water age and residual circulation were computed for different hydrodynamic scenarios, with representative summer and winter periods and, consequently, with different forcings (tide, river flow or wind), in order to identify possible stagnation areas. Results show that the tide and the river flows are the most important forcings in the water renewal of the PEC. Two possible stagnation areas were identified in all scenarios, which presented lower renewal rates and higher water ages when compared to the other regions, namely, the Pinheiros bay region and the region near to Paranaguá city. During the summer and taking into account all the forcings, renewal rates in the Pinheiros Bay region and near the city of Paranaguá are less than 95% whereas in the other regions of the PEC, the values are higher than 95%.
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Hepatocellular carcinoma (HCC), as a global malignant tumor with high morbidity and mortality, has seriously endangered human health. In the treatment of HCC, chemotherapy resistance is the knotty problem. Long non-coding RNA (lncRNA), as a new multifunctional molecule with complex mechanisms, plays a role in the biological processes of HCC, such as development, progression, invasion and migration, and participates in the complex mechanism of drug resistance through abnormal regulation of gene expression. In this paper, to seek for the new method for solving the chemotherapeutic resistance of HCC based on the research of lncRNA, the effect and mechanism of lncRNA on chemotherapeutic resistance of HCC were summarized.
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@#[Abstract] Objective: To investigate the effect of 18H12, a functional monoclonal antibody that can target gastric cancer stem cells, on the self-renewal and invasion ability of gastric cancer cells. Methods: The gastric cancer cell line PAMC-82 was used as cell model, the expression of ENO1 (enolase-1) on the membrane surface of its parental cells and enriched stem cells by sphere culture was detected by Flow cytometry. Flow cytometry was used to separate ENO1+ cells and ENO1- cells to detect their self-renewal ability and invasion ability. With the commercial ENO1 antigen and antibody as the samples, CoIP (co-immunoprecipitation) was used to verify whether 18H12 antibody targeting ENO1 could able to accurately recognize ENO1. After being treated with 18H12 for 12 h, 24 h and 48 h, the selfrenewal and invasion ability of PAMC-82 cells were detected by methylcellulose pelletization experiment and Transwell chamber assay, respectively. Results: Flow cytometry showed that the expression of ENO1 on the membrane surface of PAMC-82 sphere cells was significantly higher than that of its parental cells (P<0.01), so ENO1 could be a potential target for targeting gastric cancer stem cells. The self-renewal ability and invasion ability of the sorted ENO1+ cells were significantly stronger than those of the ENO1- cells and the parental cells (P<0.05 or P<0.01). 18H12 antibody could accurately recognize ENO1, which was consistent with the commercial antibody recognition band. 18H12 could significantly inhibit self-renewal ability and invasion ability of PAMC-82 cells (P<0.01). Conclusion: Monoclonal antibody 18H12 can significantly inhibit the self-renewal and invasion of gastric cancer stem cells and is expected to be a candidate antibody drug targeting gastric cancer stem cells.
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BACKGROUND: Wnt signaling pathway plays an important role in the regulation of stem cells, but its regulatory effect on limbal stem cells is not well defined. OBJECTIVE: To investigate the regulation of limbal stem cells via Wnt signaling pathway and its function in the treatment of limbal stem cell deficiency. METHODS: Rat limbal segments were digested with Dispase and trypsin/EDTA and then single limbal stem cells were seeded in 3D-Matrigel. In experimental group LiCl (500 μmol/L) was added to the culture system. Control group received no LiCl. The expression levels of p63α, CK12, CEBPδ and Ki67 in limbal stem cells were detected by qRT-PCR on the 7th day of culture. The expression level of β-catenin in limbal stem cells was detected by immunofluorescence staining. The rat model of limbal stem cell deficiency was made by alkali burn method. Rats in treatment group were treated with Wnt-activated limbal stem cells by subconjunctival injection. Rats in control group were treated with PBS. Rats were checked by slit lamp every day. On the 4th day after treatment, the immunofluorescence staining and hematoxylin-eosin staining were applied to evaluate the repair of limbus. RESULTS AND CONCLUSION: (1) The limbal stem cells aggregated in 3D-Matrigel. β-Catenin was negative in the control group. β-Catenin was found in the cytoplasm and nucleus of the limbal stem cells in the experimental group. (2) qRT-PCR results showed there was no significant difference in the levels of p63α, CK12 or CEBPδ between control and experimental groups (P > 0.05). The Ki67 level in the experimental group was significantly higher than that in the control group (P < 0.05). (3) The rat models of limbal stem cell deficiency were established. The degree of corneal opacity in the treatment group was significantly lower than that in the control group (P < 0.05). Hematoxylin-eosin staining results observed that the corneal epithelial cells in the treatment group were neatly arranged, the cell size was uniform, and repair was good. Immunofluorescence staining showed that β-catenin was found in the cytoplasm and nucleus of most corneal epithelial cells in the treatment group. While β-catenin was only weakly positive in the control group, and was invisible in the cytoplasm or nucleus. (4) These results indicate that activation of Wnt signaling pathway in limbal stem cells enhances their proliferation and keeps them in an undifferentiated self-renewal state. Wnt-activated limbal stem cells can promote the regeneration of corneal epithelium and reduce the degree of corneal opacity in the treatment of limbal stem cell deficiency. The regulation of limbal stem cells via Wnt signaling pathway is expected to provide new ideas for the treatment of limbal stem cell deficiency.
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Mesenchymal stem cells (MSCs), which have the potential of self-replication and differentiation, are a very valuable cell source for stem cell-based medical therapy. Their application has opened up a new way for disease research. Although MSCs can maintain cell stemness through self-renewal, with the prolongation of cell passage and culture time, the stemness of MSCs gradually decays, and the cell aging and differentiation potential decreases gradually. Autophagy is a highly conserved cytological process that degrades the modified, excess, and deleterious cytoplasmic components in autophagosomes, which are then degraded by fusion with lysosomes. As the main intracellular degradation and recycling pathway, autophagy plays an active role in maintaining cell homeostasis, self-renewal and pluripotency. In this paper, the role of autophagy in self-renewal and maintenance of multidirectional differentiation potential of MSCs was reviewed, which laid a theoretical foundation and practical basis for the research and application of MSCs.
Subject(s)
Autophagy , Cell Differentiation , Homeostasis , Mesenchymal Stem CellsABSTRACT
@#[Abstract] Objective: To study the effect of Notch4 signaling pathway on the self-renewal capacity of cancer stem cells (CSCs) of oral squamous cell carcinoma PJ15 and PJ41 cells and its mechanism. Methods: The expression of Notch4 gene in head and neck tumors was analyzed using TCGA database. 2 μmol/L cisplatin was used to treat oral squamous cell carcinoma PJ15 and PJ41 cells for 48 h, following with the treatment of Notch pathway inhibitor DAPT for 24 h. Flow cytometry was used to detect the ratio of CSCs, Western blotting and qPCR were used to detect the expressions of CSCs markers (Sox2, Bmi-1, Oct4, Nanog) and downstream genes in Notch4 signaling pathway (JAG1, HEY1, HEY2, HES1, HES2, DLL4, etc.). Notch4 was knocked down by siRNA technology. Notch4 was silenced with siRNA technology. Western blotting and qPCR were used to detect the effect of si-Notch4 and cisplatin on the expression level of CSCs markers. The stem cell pelletingtestwasusedtodetecttheself-renewalabilityof CSCs. Results: Notch4 gene was highly expressed in head and neck tumor tissues (P=0.046). After cisplatin treatment, compared with the control group, expressions of NICD4 and CSCs markers (Sox2, Bmi-1, Oct4, Nanog) as well as downstream genes of Notch4 signaling pathway (JAG1, HEY1, HEY2, HES1,HES2, DLL4, etc.) increased significantly (all P<0.05), and the proportion of ALDH1 positive cells increased significantly (P<0.05); with the further addition of DAPT, the expressions of the above genes decreased significantly (P<0.05 or P<0.01). After knocking down Notch4, compared with the control group, the size and number of spheres of PJ15 cells [1.33±0.47] vs [8.00±0.82], P<0.01) and PJ41 cells ([1.00±0.82] vs [7.67±1.25], P<0.01) were significantly lower than that of the control group; after the addition of 2 μmol/L DDP for 24 h, there was no significant difference in the expressions of Nanog and Bmi-1 gene between si-Notch4 group and control group. Conclusion:Activation of Notch4 signaling pathway can enhance the self-renewal ability of CSCs in oral squamous cell carcinoma PJ15 and PJ41 cells.
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Purpose: Glaucoma affects different aspects of vision including visual field. This prospective observational study aims to collect details of driving license (DL) renewal procedure (in an urban metro in India) among patients with diagnosed glaucoma and the method of reporting of vision-related requirements during renewal. Methods: One-hundred patients with diagnosed glaucoma above 40 years, having valid DL (with at least one renewal cycle), were included. Patients with other ocular comorbidities were excluded. Driving Habits Questionnaire and a questionnaire about license renewal were administered. Driving eligibility was compared to international guidelines. Results: Study population included patients with 69% early, 29% moderate, and 2% advanced glaucoma. Sixteen percent of patients had stopped driving. Legal license renewal procedure was bypassed by 45%. Form-1 was not submitted by 43% and 49% did not submit Form-1A at the time of renewal. Only 7.01% mentioned about glaucoma in the self-declaration form. None were asked about their visual field during renewal. Among 61 patients who submitted a medical certificate, the undersigning doctor was an ophthalmologist in only six patients. Thirty percent patients with valid Indian DL would not have satisfied International College of Ophthalmologists guidelines. Driving difficulties were experienced by 44%, more so in advanced glaucoma (F (1, 82) = 22.12, P < 0.001). Conclusion: Vision-related testing at the time of renewal of DL is inadequate in India. Chronic eye diseases such as glaucoma are commonly not self-declared or detected at pre-renewal testing. Clear-cut guidelines about visual requirements and implementation are required to prevent road traffic events because of vision-related errors.
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Objective@#To investigate the effect of down-regulation of insulin-like growth factor 2 (IGF2) gene on the biological characteristics of HCT116 colon cancer stem cells (CSCs).@*Methods@#Flow cytometry sorting technology was used to isolate CSCs from colon cancer cell line HCT116 by a monoclonal antibody against CD133; serum free floating culture assay was used for the enrichment of CSCs. The proportion of CD133+ cells was analyzed by flow cytometry; CSCs were identified by sphere culturing, immunofluorescence analysis and soft agar clone formation. RT-qPCR method was used to examine transcriptional level of IGF2 gene in CSCs. Western blotting was used to examine IGF2 protein expression in CSCs. siRNA was used to establish IGF2 transient knock down model in CSCs. Cell proliferation array, cell cycle and apoptosis analysis, cell invasion array and colony forming assay were used to further examine the role of IGF2 on the biological characteristics of colon CSCs.@*Results@#CSCs were successfully isolated from HCT116 cell lines, which were cultured to form cell spheres in serum-free stem cell culture medium. We found that the morphology of sphere-forming-like cells after several passages maintained the same characteristics as that of the first passage. The results of immunofluorescence showed that CSC markers including CD133 and ALDH continued positively expressing on the cell surface of CSCs, and flow cytometry analysis showed that more than 90% of the spheroid cells remained CD133 positive. The clone formation rate of non-CSCs group and CSCs group were (28.10±2.66)% and (43.73±2.30)% respectively, with significant difference (P<0.01). The RT-qPCR results showed that the transcriptional level IGF2 gene in non-CSCs group and CSCs group were (1.06±0.24) and (2.17±0.51) respectively, with significant difference (P<0.05). The western blot results showed that the protein expression of IGF2 in CSCs group and non-CSCs group were (1.10±0.55) and (2.14±0.23) respectively, with significant difference (P<0.05). Knockdown of IGF2 significantly decreased the percentage of CD133+ cells in CSCs and cell proliferation (P<0.01). Knockdown of IGF2 increased the percentage of G2/M phase (23.46% of siNC group vs 60.14% of siIGF2 group) and cell apoptosis (2.80% of siNC group vs 40.70% of siIGF2 group), while decreased the percentage of G0/G1 phase (40.77% of siNC group vs 17.73% of siIGF2 group). The invasion results showed that the number of cells penetrating into the basement surface in siNC group and siIGF2 group was (109.00±16.37) and (54.00±8.19) respectively, with significant difference (P<0.01). The rate of sphere-forming of colon CSCs in siNC group and siIGF2 group were (51.70±7.42)% and (21.27±2.35)% respectively, with significant difference (P<0.01). The clone formation rate of siNC group and siIGF2 group were (37.20±3.87)% and (18.23±2.25)% respectively, with significant difference (P<0.01).@*Conclusion@#IGF2 gene plays an important role in maintaining the biological characteristics of colon cancer stem cells and promoting self-renewal and stemness of colon CSCs.