Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2 and the application of defined 3D hAT2 cultures as models for respiratory diseases

Prognostic significance of CD44s expression in resected non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; <it>n </it>= 82) and squamous cell carcinoma (SCC; <it>n </it>= 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically.</p> <p>Results</p> <p>High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (<it>P <</it>0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (<it>P </it>= 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (<it>P </it>< 0.001), high-grade tumor differentiation (<it>P = </it>0.046), and high CD44s expression (<it>P = </it>0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (<it>P = </it>0.015). No significant association was found between CD44s and clinical outcome (<it>P </it>= 0.311).</p> <p>Conclusions</p> <p>High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.</p

Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer

<p>Abstract</p> <p>Backgrounds</p> <p>Cisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers.</p> <p>Methods</p> <p>In 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS).</p> <p>Results</p> <p>The median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin level</p> <p>Conclusion</p> <p>All of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.</p

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Análisis de las Estrategias Metodológicas implementadas por el docente en el desarrollo del proceso de enseñanza- aprendizaje en la disciplina de Geografía e Historia de Nicaragua y su Didáctica en los alumnos/as de Primer año “B” del turno regular de Formación Inicial Docente en la Escuela Normal Central de Managua Alesio Blandón Juárez durante el I semestre del Curso Escolar 2016

El presente trabajo de investigación tiene como finalidad analizar la efectividad que tienen las Estrategias Metodológicas implementadas por el docente en el desarrollo del proceso de enseñanza- aprendizaje en la disciplina de Geografía de Nicaragua y su Didáctica en los alumnos/as de Primer año “B” del turno regular de Formación Inicial Docente en la Escuela Normal Central de Managua Alesio Blandón Juárez durante el I semestre del Curso Escolar 2016. Dicho trabajo de investigación tiene un enfoque naturista o cualitativo, es una vía de transformación social, a través de la cual el ser humano descubre la realidad que le rodea, determina los medios y procedimientos para actuar sobre ella y transformarla de acuerdo a una intensión social. Los procesos de investigación cualitativa, tienen como finalidad primordial la generación y construcción de conocimientos que contribuyen al desarrollo social y personal de cada uno de los miembros de una comunidad. La fase de recolección de los datos de la investigación desarrollada, se realizó de dos formas: una información que se recogió mediante la observación directa del comportamiento de los informantes claves y una información que se obtuvo mediante la interrogación de algunos informantes claves. Para ello, primeramente el investigador realizo una inmersión en el campo de trabajo, con el propósito de identificar los lugares adecuados para recoger y producir la información necesaria y requerid