Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice.

Durable reconstitution of the distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising therapy for diseases that result from alveolar damage. Here, we differentiate murine PSCs into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. After transplantation, these progenitors mature in the distal lung, assuming the molecular phenotypes of alveolar type 2 (AT2) and type 1 (AT1) cells. After months in vivo, donor-derived cells retain their mature phenotypes, as characterized by single-cell RNA sequencing (scRNA-seq), histologic profiling, and functional assessment that demonstrates continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lung's facultative progenitor and differentiated epithelial cell compartments with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy that can be utilized to better understand the mechanisms and utility of engraftment.

Optimization of underground open intermediary space comfort in TOD complexes: A case study of Chongqing, China.

Rapid urbanization drives social development, but at the same time brings sustainable development Rapid urbanization drives social development, but at the same time brings sustainable development advantages of expanding underground space and relieving urban traffic congestion. High quality TOD complexes with natural elements in the intermediary space have been considered as one of the important means to address sustainable urban development. Nevertheless, intermediary spaces in TOD complexes face various challenges, such as significant contradictory factors in their physical environment spaces. This study classifies the underground open intermediary space into four types according to the characteristics of TOD complexes. And for these four types'Cthe physical environment-generated by various influencing factors of planar geometric, three-dimensional geometric, and detailed construction elements-is simulated using a numerical simulation method based on a static Taguchi experiment. The results demonstrate that space shape is a primary influencing factor for luminous and thermal environments; the window-atrium ratio (W/A ratio) and hole-atrium ratio (H/A ratio) comprise contradictory factors between the luminous and thermal environments of these spaces; profile inclination angle and sunken plaza height are primary impact factors for the acoustic environment; and skylight type has minimal influence on the physical environment. On average, their luminous and acoustic environment comfort can be improved by 200%; whereas, their thermal environment comfort can be improved by 21% and the potential for optimizing it in their shallow space (underground space depth ≤ 10 m) is relatively low. Subsequently, the necessity of comfort optimization as the passive optimization design of underground open intermediary spaces' physical environment in TOD complexes in the future is discussed. Finally, the feasible path and prospect of how to improve the livability and comfort of the spatial physical environment of TOD complexes are discussed and prospected.

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiation and Function.

Differential chromatin accessibility accompanies and mediates transcriptional control of diverse cell fates and their differentiation during embryogenesis. While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Here, we demonstrate that the paired domain zinc finger transcriptional regulators PRDM3 and PRDM16 regulate chromatin accessibility to mediate cell differentiation decisions during lung morphogenesis. Combined deletion of Prdm3 and Prdm16 in early lung endoderm caused perinatal lethality due to respiratory failure from loss of AT2 cell function. Prdm3/16 deletion led to the accumulation of partially differentiated AT1 cells and loss of AT2 cells. Combination of single cell RNA-seq, bulk ATAC-seq, and CUT&RUN demonstrated that PRDM3 and PRDM16 enhanced chromatin accessibility at NKX2-1 transcriptional targets in peripheral epithelial cells, all three factors binding together at a multitude of cell-type specific cis-active DNA elements. Network analysis demonstrated that PRDM3/16 regulated genes critical for perinatal AT2 cell differentiation, surfactant homeostasis, and innate host defense. Lineage specific deletion of PRDM3/16 in AT2 cells led to lineage infidelity, with PRDM3/16 null cells acquiring partial AT1 fate. Together, these data demonstrate that NKX2-1-dependent regulation of alveolar epithelial cell differentiation is mediated by epigenomic modulation via PRDM3/16.

Surfactant protein C mutation links postnatal type 2 cell dysfunction to adult disease.

Mutations in the gene SFTPC, encoding surfactant protein C (SP-C), are associated with interstitial lung disease in children and adults. To assess the natural history of disease, we knocked in a familial, disease-associated SFTPC mutation, L188Q (L184Q [LQ] in mice), into the mouse Sftpc locus. Translation of the mutant proprotein, proSP-CLQ, exceeded that of proSP-CWT in neonatal alveolar type 2 epithelial cells (AT2 cells) and was associated with transient activation of oxidative stress and apoptosis, leading to impaired expansion of AT2 cells during postnatal alveolarization. Differentiation of AT2 to AT1 cells was also inhibited in ex vivo organoid culture of AT2 cells isolated from LQ mice; importantly, treatment with antioxidant promoted alveolar differentiation. Upon completion of alveolarization, SftpcLQ expression was downregulated, leading to resolution of chronic stress responses; however, the failure to restore AT2 cell numbers resulted in a permanent loss of AT2 cells that was linked to decreased regenerative capacity in the adult lung. Collectively, these data support the hypothesis that susceptibility to disease in adult LQ mice is established during postnatal lung development, and they provide a potential explanation for the delayed onset of disease in patients with familial pulmonary fibrosis.

IGF1R controls mechanosignaling in myofibroblasts required for pulmonary alveologenesis.

Ventilation throughout life is dependent on the formation of pulmonary alveoli, which create an extensive surface area in which the close apposition of respiratory epithelium and endothelial cells of the pulmonary microvascular enables efficient gas exchange. Morphogenesis of the alveoli initiates at late gestation in humans and the early postnatal period in the mouse. Alveolar septation is directed by complex signaling interactions among multiple cell types. Here, we demonstrate that IGF1 receptor gene (Igf1r) expression by a subset of pulmonary fibroblasts is required for normal alveologenesis in mice. Postnatal deletion of Igf1r caused alveolar simplification, disrupting alveolar elastin networks and extracellular matrix without altering myofibroblast differentiation or proliferation. Moreover, loss of Igf1r impaired contractile properties of lung myofibroblasts and inhibited myosin light chain (MLC) phosphorylation and mechanotransductive nuclear YAP activity. Activation of p-AKT, p-MLC, and nuclear YAP in myofibroblasts was dependent on Igf1r. Pharmacologic activation of AKT enhanced MLC phosphorylation, increased YAP activation, and ameliorated alveolar simplification in vivo. IGF1R controls mechanosignaling in myofibroblasts required for lung alveologenesis.

In Vivo Generation of Lung and Thyroid Tissues from Embryonic Stem Cells Using Blastocyst Complementation.

Rationale: The regeneration and replacement of lung cells or tissues from induced pluripotent stem cell- or embryonic stem cell-derived cells represent future therapies for life-threatening pulmonary disorders but are limited by technical challenges to produce highly differentiated cells able to maintain lung function. Functional lung tissue-containing airways, alveoli, vasculature, and stroma have never been produced via directed differentiation of embryonic stem cells (ESCs) or induced pluripotent stem cells. We sought to produce all tissue components of the lung from bronchi to alveoli by embryo complementation.Objectives: To determine whether ESCs are capable of generating lung tissue in Nkx2-1-/- mouse embryos with lung agenesis.Methods: Blastocyst complementation was used to produce chimeras from normal mouse ESCs and Nkx2-1-/- embryos, which lack pulmonary tissues. Nkx2-1-/- chimeras were examined using immunostaining, transmission electronic microscopy, fluorescence-activated cell sorter analysis, and single-cell RNA sequencing.Measurements and Main Results: Although peripheral pulmonary and thyroid tissues are entirely lacking in Nkx2-1 gene-deleted embryos, pulmonary and thyroid structures in Nkx2-1-/- chimeras were restored after ESC complementation. Respiratory epithelial cell lineages in restored lungs of Nkx2-1-/- chimeras were derived almost entirely from ESCs, whereas endothelial, immune, and stromal cells were mosaic. ESC-derived cells from multiple respiratory cell lineages were highly differentiated and indistinguishable from endogenous cells based on morphology, ultrastructure, gene expression signatures, and cell surface proteins used to identify cell types by fluorescence-activated cell sorter.Conclusions: Lung and thyroid tissues were generated in vivo from ESCs by blastocyst complementation. Nkx2-1-/- chimeras can be used as "bioreactors" for in vivo differentiation and functional studies of ESC-derived progenitor cells.

Progress of Intramural Metastasis of Esophageal Squamous Cell Carcinoma / 肿瘤防治研究

Intramural metastasis (IM) is defined as metastatic tumor from the primary tumor to the digestive tracts through the intramural lymphatic system. It can occur in esophageal, gastric and colorectal carcinomas, especially in esophageal squamous cell carcinoma. The combination of histological morphological evaluation and molecular pathology can assist in the identification of IM and multiple primary carcinomas (MPCs). IM is usually associated with a poor prognosis and also affects the treatment. This article reviews the anatomical and histological basis, clinicopathological characteristics, treatment and prognosis of IM in ESCC, the identification of IM and MPCs and how to improve the detection rate of IM, to guide accurate diagnosis and treatment.

Action Mechanism of Main Components from Glycyrrhizae Radix et Rhizoma in Improving Insulin Resistance in L6 Rat Myoblasts / 中国实验方剂学杂志

Objective::To determine whether the main components of Glycyrrhizae Radix et Rhizoma can improve insulin resistance by regulating glycogen synthesis, glycolysis pathway and fatty acid synthesis in myoblasts of L6 rat myoblasts. Method::Insulin resistance (IR) model of L6 rat myoblasts was established through incubation with 0.05 mmol·L-1 palmitic acid (PA) for 9 hours. Normal group, model group, glycyrrhizic acid (GA, 25 μmol·L-1) group, 18β-glycyrrhetinic acid (18β-GA, 25 μmol·L-1) group, isoliquiritigenin (ILG, 25 μmol·L-1) group and isoliquiritin (ILQ, 25 μmol·L-1) group were set up, glucose content in supernatant of cell culture medium was detected by glucose kit, myoblasts glycogen content was determined by glycogen detection kit, protein expression levels of Sterol regulatory element binding protein-1c(SREBP-1c), fatty acid synthetase (FAS) and glycogen synthase kinase3β(GSK3β) were detected by Western blot, and the mRNA expressions of key enzymes in glycolysis were detected by quantitative real-time fluorescence polymerase chain reaction(Real-time PCR). Result::Compared with those in the normal group, the glucose consumption rate was significantly down-regulated in model group (P<0.01), the glycogen content was decreased (P<0.05), the protein expressions of Sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) were decreased (P<0.05, P<0.01), the mRNA expressions of fructose phosphate kinase 1 (PFK1), pyruvate kinase (PK) and hexokinase (HK) were down-regulated (P<0.05), and the protein expression of glycogen synthase kinase 3 (GSK3β) protein was increased (P<0.05). Compared with model group, GA, 18β-GA and ILG could significantly increase glycogen content in myoblasts of IR-L6 rats (P<0.05, P<0.01). GA, 18β-GA and ILQ could significantly increase the expression of SREBP-1c (P<0.05, P<0.01), and GA, 18β-GA, ILG and ILQ could significantly increase the expression of FAS (P<0.05, P<0.01), the mRNA expressions of PFK1, PK and HK (P<0.05, P<0.01), and down-regulate the protein expression of GSK3β (P<0.05). Conclusion::The main components of licorice improve the insulin resistance by promoting glycolysis and glycogen synthesis and regulating fatty acid synthesis.

"Medium and Long-term Plan for the Prevention and Control of Chronic Non-communicable Diseases in Shanghai(2018-2030)" in the perspective of public health / 上海预防医学

The "Medium and Long-term Plan for the Prevention and Control of Chronic Non-communicable Diseases in Shanghai (2018-2030)" was officially released in August 2018.From the perspective of public health, this paper analyzes the background of the plan from the epidemic situation, response and challenges Shanghai City is facing, expounds the comprehensive prevention and control system of chronic diseases including four functional systems, and explains the key preventive and control measures on the different stages of chronic diseases, comparing the evaluation indicators with those of the national plan.This paper will help to better understand the new blueprint for the prevention and control of chronic diseases in Shanghai in the next ten years.

Association of estrogen receptor α gene polymorphisms with hepatitis B cirrhosis / 临床肝胆病杂志

At present, hepatitis B cirrhosis still has a major impact on public health and national development. The development and progression of hepatitis B cirrhosis is associated with estrogen. Estrogen acts by binding to estrogen receptors, and the expression and functional status of estrogen receptors are affected by estrogen receptor gene polymorphisms. This article mainly introduces the structure and biological characteristics of estrogen and estrogen receptor α gene and their association with the pathogenesis of hepatitis B cirrhosis, and it is pointed out that the abnormal expression of estrogen may be associated with the development and progression of hepatitis B cirrhosis. However, due to the differences in genetic loci, environment, and location between studies, the results of the association of estrogen receptor α gene polymorphisms with hepatitis B cirrhosis may not be completely consistent.

Proteasome dysfunction in alveolar type 2 epithelial cells is associated with acute respiratory distress syndrome.

Proteasomes are a critical component of quality control that regulate turnover of short-lived, unfolded, and misfolded proteins. Proteasome activity has been therapeutically targeted and considered as a treatment option for several chronic lung disorders including pulmonary fibrosis. Although pharmacologic inhibition of proteasome activity effectively prevents the transformation of fibroblasts to myofibroblasts, the effect on alveolar type 2 (AT2) epithelial cells is not clear. To address this knowledge gap, we generated a genetic model in which a proteasome subunit, RPT3, which promotes assembly of active 26S proteasome, was conditionally deleted in AT2 cells of mice. Partial deletion of RPT3 resulted in 26S proteasome dysfunction, leading to augmented cell stress and cell death. Acute loss of AT2 cells resulted in depletion of alveolar surfactant, disruption of the alveolar epithelial barrier and, ultimately, lethal acute respiratory distress syndrome (ARDS). This study underscores importance of proteasome function in maintenance of AT2 cell homeostasis and supports the need to further investigate the role of proteasome dysfunction in ARDS pathogenesis.

The effect of hypoxia on gene expression and signaling pathway in 3D cultured cerebral cortex cells / 中国医师杂志

Objective@#To explore potential therapeutic targets for neonatal hypoxic brain injury, we analyzed the effects of hypoxia on the gene expression profiles and signaling pathway in 3D cultured cerebral cortex cells.@*Methods@#R studio software was used to analyze the differentially expressed genes of hypoxia treated cerebral cortex cell data (GSE112137) which was downloaded from GEO database. Gene Oncology and KEGG software were used to enrich the molecular function, biological process and signaling pathways of differentially expressed genes. Then String and Cytoscape software were adapted to analyzed gene interaction network between these genes.@*Results@#There were 395 increasing genes and 185 decreasing genes (Change Fold≥2) were identified in hypoxic cerebral cells compared with the control groups. Most elevated genes were mainly related with molecular function including dioxygenase activity, isomerase activity and misfolded protein binding, while the decreasing genes were enriched in RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding. Biological process enrichment analysis revealed that hypoxia up-regulated genes were associated with endoplasmic reticulum stress, oxidation-reduction process and glycolysis, while down-regulated genes were involved in the progress of neural development and cell differentiation. KEGG pathway enrichment results indicated hypoxia increasing genes were mainly related with endoplasmic reticulum protein processing, glycolysis, amino acid biosynthesis, and decreasing genes were mainly enriched in Parkinson′s disease signaling pathway.@*Conclusions@#Hypoxia in human cerebral cortex cells could cause endoplasmic reticulum stress, protein misfolding and metabolic abnormalities, inhibited the development of neuron cells. Drugs targeting these process may be beneficial to alleviate cerebral hypoxia injury.

The effect of hypoxia on gene expression and signaling pathway in 3D cultured cerebral cortex cells / 中国医师杂志

Objective To explore potential therapeutic targets for neonatal hypoxic brain injury,we analyzed the effects of hypoxia on the gene expression profiles and signaling pathway in 3D cultured cerebral cortex cells.Methods R studio software was used to analyze the differentially expressed genes of hypoxia treated cerebral cortex cell data (GSE112137) which was downloaded from GEO database.Gene Oncology and KEGG software were used to enrich the molecular function,biological process and signaling pathways of differentially expressed genes.Then String and Cytoscape software were adapted to analyzed gene interaction network between these genes.Results There were 395 increasing genes and 185 decreasing genes (Change Fold ≥2) were identified in hypoxic cerebral cells compared with the control groups.Most elevated genes were mainly related with molecular function including dioxygenase activity,isomerase activity and misfolded protein binding,while the decreasing genes were enriched in RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding.Biological process enrichment analysis revealed that hypoxia up-regulated genes were associated with endoplasmic reticulum stress,oxidation-reduction process and glycolysis,while down-regulated genes were involved in the progress of neural development and cell differentiation.KEGG pathway enrichment results indicated hypoxia increasing genes were mainly related with endoplasmic reticulum protein processing,glycolysis,amino acid biosynthesis,and decreasing genes were mainly enriched in Parkinson's disease signaling pathway.Conclusions Hypoxia in human cerebral cortex cells could cause endoplasmic reticulum stress,protein misfolding and metabolic abnormalities,inhibited the development of neuron cells.Drugs targeting these process may be beneficial to alleviate cerebral hypoxia injury.

The expression and clinical significance of immune checkpoints in acute myeloid leukemia / 中国医师杂志

Objective To find potential effective immunotherapy targets for acute myeloid leukemia (AML) by analyzing the expression and clinical significance of different immune checkpoints.Methods Gene expression profiles of AML cell lines (GSE57083) and tissues (GSE37642) were downloaded from GEO database.Then different immune checkpoints expression and clinical significance were analyzed with R studio and GraphPad software.Results In 16 AML cell lines,the expression rank of 11 immune checkpoints genes was LGALS9,PVRL2,PVR,PDCD1,TIM3,CTLA4,PDL1,GITR,LAG3,PDL2,GITRL,and among which LGALS9,PVRL2,GITR had larger variation between different cells.In AML tissues,the expression rank of immune checkpoint was LGALS9,PVRL2,TIM3,PDCD1,CTLA4,LAG3,GITR,PDL1,PVR,GITRL,PDL2.Survival analysis revealed high expression of PVR and LGALS9 was associated with poor prognosis,while the survival time had no significant difference in other genes.Conclusions PVR is highly expressed in AML tumor cells,and LGALS9 is highly expressed in both AML tumor cells and tissues.High expression of PVR and LGALS9 is associated with poor prognosis of AML patients,which may be a potential effective immunotherapy target for AML.

The expression and clinical significance of ENPP2 in acute myeloid leukemia / 中国医师杂志

Objective To analyze the expression and clinical significance of exonucleotide pyro-phosphatase/phosphodiesterase family member 2 (ENPP2) in acute myeloid leukemia (AML), and to ex-plore its potential molecular mechanism. Methods The expression profiles of ENPP2 in different normal tissues was analyzed with GTEx database. Rstudio and Graphpad were used to analyze ENPP2 expression, genomic mutations and survival curve in data from GEO and TCGA databases, and the signaling pathway as-sociated with ENPP2 expression were further analyzed with GSEA enrichment software. Results In normal tissues, ENPP2 was mainly expressed in fat, brain and uterus;the expression in acute myeloid leukemia tis-sues was higher than that in donors. Only 0. 5％ of patients in 187 TCGA genomic data had gene amplifica-tion, there was no gene mutations and deletions. ENPP2 expression in recurrent AML was significantly high-er than primary patients, and its high expression was associated with poor prognosis. Gene enrichment anal-ysis shows high ENPP2 group isenriched in autoimmune diseases, cytokine receptor activation pathway, and low ENPP2 was enriched in DNA replication, cell cycle pathways. ENPP2 was also involved in the pathway that associated with retinoic acid and glucocorticoids treatment. Conclusions ENPP2 is highly expressed in AML patients and is associated with recurrence and poor prognosis of AML. The main molecular mecha-nism of ENPP2 in AML may be related to autoimmune response and drug treatment response, ENPP2 is a potential therapy target of AML.

Risk factor changes for chronic disease before and after healthy walking intervention in occupational population in Shanghai / 上海预防医学

[Objective]To investigate the influence of healthy walking intervention on risk factors of noncommunicable chronic disease in occupational population, and to explore the suitable mode of exercise intervention for occupational population in Shanghai. [Methods]Before and after healthy walking intervention were compared the changes of body weight, BMI, waist circumference, body fat rate, visceral fat index, over-weight and obesity rate, central obesity rate, blood-pressure controlling rate. [Results]Weight, BMI, waist circumference, body fat percentage, viscera index, SBP and DBP all reduced after100 days of healthy walking, and the results were (1.52 ± 2.75) kg (Z =-21.99, P < 0.01) , (0.55 ±1.03) kg/m2 (Z =-21.64, P<0.01) , (2.10±5.27) cm (Z =-17.62, P<0.01) , (0.31±4.59) ％ (Z=-3.48, P < 0.01) , (0.12 ± 1.99) (Z =-2.70, P < 0.01) , (2.51 ± 10.87) mm Hg (Z =-9.35, P <0.01) and (1.67±8.26) mm Hg (Z =-9.06, P < 0.01). The rate of over-weight and obesity decreased7.86％, the rate of central obesity decreased 6.92％, and the rate of blood-pressure controlling increased2.72％. There were significant difference between the three indicators before and after healthy walking (χ2= 916.48, P< 0.01; χ2= 585.90, P < 0.01; χ2= 366.37, P < 0.01). [Conclusion] Healthy walking could reduce occupational population' s over-weight and obesity rate, central obesity rate, and increase blood-pressure controlling rate. The risk factors of un-communicable chronic disease have improved significantly. Healthy walking plays a positive role in the prevention and control of chronic diseases.

The expression of PDCD5 in peripheral blood of influenza A (H1N1) patients and the correlation with the severity of disease / 医学研究生学报

Objective The influenza A (H1N1) virus has the characteristic of strong infectiousness and variation. It can threaten the lives of patients. In this paper,we investigated the expression of programmed cell death molecule 5 (PDCD5) in peripheral blood of patients with influenza A (H1N1) and its correlation with the severity of disease. Methods The data of 104 patients with influenza A (H1N1) treated in Affiliated Hospital of Hebei University from January 2015 to December 2017 were analyzed retrospectively. The 104 patients were divided into the mild H1N1 group (n=78) and the severe H1N1 group (n=26). At the same time,104 healthy physical examination subjects were selected as control group. The blood routine,lymphocyte count and PDCD level were observed in three groups. Results The number of leukocytes,neutrophils and lymphocytes of the mild H1N1 group and severe H1N1 group were significantly lower than those of the control group (P<0.05). The number of leukocytes,neutrophils and lymphocytes of the severe H1N1 group were significantly lower than those of the mild H1N1 group (P<0.05). There was no significant difference in mononuclear cells between three groups (P>0.05). The levels of PDCD5 and lymphocyte apoptosis rate of the mild H1N1 group and severe H1N1 group were significantly higher than those of the control group (P<0.05) ,the severe H1N1 group was significantly higher than the mild H1N1 group (P<0.05). The total T cells,CD4+T cells and CD8+T cells of the mild H1N1 group and severe H1N1 group were significantly lower than those of the control group (P<0.05). The total T cells,CD4+T cells and CD8+T cells of the severe H1N1 group were significantly lower than those of the mild H1N1 group and con-trol group (P<0.05). The level of PDCD5 was positively correlated with the severity of disease and the rate of lymphocyte apoptosis (r=0.872,0.904,P<0.05),and negatively correlated with total T cells,CD4+T cells and CD8+T cells (r=-0.842,-0.805,-0.877,P<0.05). The sensitivity,specificity and area under the curve of PDCD5 to prediction of severe type H1N1 were 92.31%,97.25% and 0.941,respectively. Conclusion The level of peripheral blood PDCD5 in patients with influenza A (H1N1) virus in-fection is associated with the severity of the disease,and it can be considered as an important biomarker to predict severe influenza A (H1N1).

Effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells

Objective: To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells. Methods: Regenerated tissue extracts after liver injury were used to induce SK-HEP1 cells after enrichment, their effects on the proliferation, differentiation, migration and invasion of SK-HEP1 cells were observed through in vitro cell culture, MTT, flow cytometry and transwell assays. Results: In response to the action of regenerated tissue extracts after liver injury, SK-HEP1 cells were blocked in G

Effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells

Objective:To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells.Methods:Regenerated tissue extracts after liver injury were used to induce SK-HEP1 cells after enrichment, their effects on the proliferation, differentiation, migration and invasion of SK-HEP1 cells were observed through in vitro cell culture, MTT, flow cytometry and transwell assays.Results:In response to the action of regenerated tissue extracts after liver injury, SK-HEP1 cells were blocked in GConclusions:To a certain extent, regenerated tissue extracts after liver injury can inhibit the proliferation, differentiation, migration and invasion of hepatoma cells, showing an important potential of being a differentiating agent for the treatment of liver cancer.

EMC3 coordinates surfactant protein and lipid homeostasis required for respiration.

Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. EMC3 was essential for the processing and routing of surfactant proteins, SP-B and SP-C, and the biogenesis of the phospholipid transport protein ABCA3. Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth.