MMP7 expression regulated by endocrine therapy in ERβ-positive colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Many studies have shown that colon cancer is an estrogen-dependent carcinoma. This study explored the efficacy of endocrine therapy in colon cancer cells with high metastatic potential (HT29). We investigated the proliferation of HT29 cells after exposure to endocrine therapy (tamoxifen) and 5-FU.</p> <p>Methods</p> <p>Apoptosis was evaluated using flow cytometry. The expression of matrix metalloproteinases 7 (MMP-7) and estrogen receptor beta (ERβ) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. The migration capability of treated cells was determined with wound scratch assay.</p> <p>Results</p> <p>Tamoxifen alone, 5-FU alone, and the combination of the two drugs can significantly inhibit HT29 cell proliferation and migration, block the cells in G₂/M phase and induce cell apoptosis. These drugs also can down-regulate MMP7 and ERβ expression.</p> <p>Conclusion</p> <p>Our findings suggest that endocrine therapy is an efficient therapy for inhibiting ERβ-positive colon cancer cell proliferation and migration via down-regulation of MMP7.</p

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

Objective: To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design: A retrospective single-institution cohort study. Patients: The perioperative records of&nbsp;71&nbsp;patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors’ institution between November&nbsp;2012 and June&nbsp;2019 were retrospectively analyzed. Methods: The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results: The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p&nbsp;=&nbsp;0.02, HR&nbsp;=&nbsp;2.472, 95%&nbsp;CI&nbsp;[1.156, 5.289]), target therapy (p &lt; 0.01, HR&nbsp;=&nbsp;0.186, 95%&nbsp;CI [0.073, 0.477]), and radiotherapy (p&nbsp;=&nbsp;0.006, HR&nbsp;=&nbsp;0.330, 95%&nbsp;CI&nbsp;[0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations: The number of enrolled patients was relatively small and patients’ treatment options varied. Conclusions: A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target

L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma

Objectives: Accurate prognosis assessment across the heterogeneous population of brain metastases is very important, which may facilitate clinical decision-making and appropriate stratification of future clinical trials. Previous studies have shown the L1 Cell Adhesion Molecule (L1CAM) is potentially involved in human malignancies of multiple different samples and unfavorable survival. However, no data of L1CAM are available for the brain metastases from lung adenocarcinoma, especially for the one with neurosurgical resection. Method: The authors investigated the L1CAM expression in cranial metastatic lesions for patients with brain metastases from lung adenocarcinoma after neurosurgical resection using tissue microarrays that were obtained from the Department of Neurosurgery at the Cancer Hospital of the Chinese Academy of Medical Sciences. Furthermore, the relationship between L1CAM expression and clinic-pathological parameters, including overall survival time, was analyzed to assess the prognostic value of L1CAM. Results: L1CAM high expression was found in&nbsp;62.30% of brain metastases from lung adenocarcinoma and significantly correlated with brain metastasis number (p&nbsp;=&nbsp;0.028) and Lung-molGPA score (p&nbsp;=&nbsp;0.042). Moreover, L1CAM expression was an independent predictor of survival for brain metastases after neurosurgical resection in a multivariate analysis. Patients with L1CAM high expression had unfavorable overall survival time (p&nbsp;=&nbsp;0.016). In addition, the multivariate analysis also showed age and extracranial transfer were also the independent prognostic factors for this type of patient with brain metastases. Conclusions: A subset of brain metastases from lung adenocarcinoma aberrantly expresses L1CAM. L1CAM is a novel independent prognostic factor for brain metastasis from lung adenocarcinoma after neurosurgical resection

Analysis of Malt Root Nutritional Components and Its Application Prospect

In this paper, the nutritional composition, active ingredients, and digestibility of malt roots were measured and analyzed and compared with those of wheat bran.The results showed that the content of protein(34.3%) and dietary fiber (39.4%) in malt roots are higher than those in wheat bran.The content of essential amino acids (8.37 g/100 g) is twice than that of wheat bran (4.03 g/100 g).The content of lysine, threonine and valine are relatively high in malt roots.Additionally, malt roots not only contain vitamin E (3.14 mg/100g),but also have a higher content of vitamin B2, B6 and B12, folic acid, and vitamin C than those in wheat bran(0.6 mg/100 g, 0.46 mg/100 g, 0.11 μg/100 g, 0.17 mg/100 g, 4.35 mg/100 g, respectively).Furthermore, the malt roots are rich in sodium, potassium, calcium, zinc, copper, phosphorus, iron, and magnesium.It also contains a high content of total polyphenols (1.09%) and a small amount of polysaccharides.At the same time, the regulatory status, application status and application prospect were analyzed from the feed, food and cosmetics fields, which provided a basis for the high-value utilization of malt root by-products

Exposures to particulate matters and childhood sleep disorders—A large study in three provinces in China

Objectives: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 μm and <1 μm, respectively) with sleep disorders in children. Methods: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012–2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. Results: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 μg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. Conclusion: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region

Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design

A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 µM respectively for PDE9 and PDE5, and about three orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors

Next-Generation Sequencing-Aided Rapid Molecular Diagnosis of Occult Macular Dystrophy in a Chinese Family

Purpose: To show early, rapid and accurate molecular diagnosis of occult macular dystrophy (OMD) in a four-generation Chinese family with inherited macular dystrophy.Methods: In the current study, we comprehensively screened 130 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the proband of a four-generation Chinese family that has suffered from maculopathy without a definitive diagnosis for over 10 years. Variants were filtered and analyzed to identify possible disease-causing variants before validation by Sanger sequencing.Results: Two heterozygous mutations—RP1L1 c.133 C &gt; T (p.Arg45Trp), which is a hot spot for OMD, and ABCA4 c.6119 G &gt; A (p.Arg2040Gln), which was identified in Stargardt’s disease were found in three patients, but neither of the mutations was found in the unaffected individuals in the same family, who are phenotypically normal or in the normal control volunteers.Conclusion: These results cannot only confirm the diagnosis of OMD in the proband, but also provide presymptomatic diagnosis of the proband’s children before the onset of visual acuity impairment and guidance regarding the prognosis and management of these patients. Heterozygous mutations of RP1L1 c.133 C &gt; T (p.Arg45Trp) and ABCA4 c.6119 G &gt; A (p.Arg2040Gln) are likely responsible for OMD. Our results further extend our current understanding of the genetic basis of OMD, and emphasize the importance of molecular diagnosis and genetic counseling for OMD

Ilustrações de cartilhas escolares na Primeira República (1889-1930) : a historiografia da educação no Espírito Santo por entre traços e espaços em branco

Este estudo objetivou investigar significados das ilustrações contidas nas cartilhas utilizadas no ensino primário, no Espírito Santo, na Primeira República, sendo que, nesse recorte temporal, procuramos tomar as duas reformas educacionais capixabas desse período: a Reforma Gomes Cardim (1908-1909) e a Reforma Atílio Vivacqua (1928-1930), como de pontos de referência em nossa investigação. Partindo de uma análise dessas ilustrações no conjunto de projetos políticos, pedagógicos, culturais e estéticos que perpassaram a escolarização no Espírito Santo, procuramos mapear o panorama que contextualizava a produção dessas ilustrações, nas esferas: social, política, econômica, cultural e educacional, procurando compreender suas relações de força e possíveis tensões; investigar se as ilustrações se relacionavam com os métodos de ensino propostos nas cartilhas, procurando estabelecer e compreender a presença ou ausência dessa relação nas práticas pedagógicas propostas para o ensino primário capixaba, nesse período; bem como, verificar quais os possíveis impactos e reflexos das Reformas Educacionais ocorridas na Primeira República, no Espírito Santo, sobre as ilustrações nas cartilhas, procurando identificá-los. Nessa investigação historiográfica, nossa ancoragem teórico-metodológica fundamenta-se em interlocuções com Marc Bloch, em sua perspectiva histórica, onde buscamos compreensão do ofício do historiador, de modo que, privilegiando a multiplicidade das fontes, procuramos tensioná-las a fim de alcançar o seu testemunho histórico; em Ginzburg, construímos fundamentos que nos permitiram tomar o método indiciário como ferramenta de pesquisa, assim como, suas reflexões sobre morfologia das imagens, por meio do método morelliano, e suas aproximações com as teorias warbuguianas, nos embasaram na abordagem histórica e leitura de fontes iconográficas; por fim, em Benjamin, procuramos compreender o contexto de produção das ilustrações, que, pertencendo ao campo de domínio da linguagem da arte, em suas várias formas de expressões, abrangem percepções de mundo, do seu momento histórico. Desse modo, analisando, historicamente, as ilustrações nas cartilhas, percebemos que as mesmas se constituem como indícios que nos oferecem pistas de propostas pedagógicas, tendências metodológicas e políticas públicas, do espaço e tempo de sua produção, circulação e utilização. Portanto, concluímos que as ilustrações têm a potência de narrativas de uma cultura escolar, ao representarem palavras, textos e temas, assim sendo, detêm valores, sentidos e significados. Portanto, enquanto objetos culturais, trazem informações, que registram pontos de vista culturais e escolares das épocas, além dos elementos que desenvolvem habilidades de leitura e escrita. À vista disso, concluímos que as ilustrações e seus significados, que lhe são atribuídos ao longo do tempo nos espaços escolares, se constituem como possibilidades que oportunizam narrativas historiográficas.This study aimed to investigate meanings of the illustrations contained in textbooks used in primary education in Espírito Santo, during the First Republic. Given this time frame, we attempted to take both capixaba educational reformations: Gomes Cardim Reformation (1908-1909) and the Atilio Vivacqua Reformation (1928-1930), as benchmarks in our investigation. Based on an analysis of these illustrations on the set of political, educational, cultural and aesthetic projects that permeated the school in Espírito Santo, we tried to map the landscape that contextualized the production of these illustrations, in the social, political, economic, cultural and educational realms, seeking to understand their power relations and possible tensions; investigating whether the illustrations were related to the teaching methods proposed in the textbooks, and trying to establish and understand the presence or absence of that relationship in the pedagogical practices proposed for the capixaba primary education in this period, as well as check what the possible impacts and outcomes of Educational Reforms occurred in the First Republic, in Espírito Santo on the illustrations in textbooks were, trying to identify them. For this historiographical research, our theoretical and methodological anchoring is based on dialogues with Marc Bloch, in his historical perspective, where we seek understanding of the historian's craft, so that in favoring the multiplicity of sources, we attempt to bend them in order to achieve their historical testimony; in Ginzburg, we build foundations that allowed us to take the evidential method as a research tool, as well as his reflections on the morphology of images, through the Morellian method and its approach to the Warburgian theories, which supported with the historical approach and the "reading" of iconographic sources; Finally, in Benjamin, we tried to understand the context of production of illustrations, which, belonging to the domain of the language of art, in its various forms of expression, encompasses perceptions of the world, and its historical moment. Thus, historically, analyzing the illustrations in textbooks, we realize that they constitute as evidence that give away hints of educational proposals, methodological trends and public policies, about the space and time of its production, circulation and use. We therefore conclude that the illustrations have the narrative power of a school culture, as they represent words, texts and themes, therefore, holding values, senses and meanings. Therefore, as cultural objects, provide information, which record cultural and school views of their times besides the elements meant to develop reading and writing skills. In view of this, we conclude that the illustrations and their meanings, which are assigned over the course of time in school spaces, are constituted as possibilities that allow for historiographical narratives.FAPE