CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.

BACKGROUND: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown. METHODS: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events. RESULTS: Endothelial ablation of Cd151 leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation. Mechanistically, CD151 restrains endothelial release of proinflammatory molecules for less leukocyte infiltration. At the subcellular level, CD151 determines the integrity of multivesicular bodies/lysosomes and confines the production of exosomes that carry cytokines such as ANGPT2 (angiopoietin-2) and proteases such as cathepsin-D. At the molecular level, CD151 docks VCP (valosin-containing protein)/p97, which controls protein quality via mediating deubiquitination for proteolytic degradation, onto endolysosomes to facilitate VCP/p97 function. At the endolysosome membrane, CD151 links VCP/p97 to (1) IFITM3 (interferon-induced transmembrane protein 3), which regulates multivesicular body functions, to restrain IFITM3-mediated exosomal sorting, and (2) V-ATPase, which dictates endolysosome pH, to support functional assembly of V-ATPase. CONCLUSIONS: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.

Regulation of the integrin αVß3- actin filaments axis in early osteogenic differentiation of human mesenchymal stem cells under cyclic tensile stress.

BACKGROUND: Integrins are closely related to mechanical conduction and play a crucial role in the osteogenesis of human mesenchymal stem cells. Here we wondered whether tensile stress could influence cell differentiation through integrin αVß3. METHODS: We inhibited the function of integrin αVß3 of human mesenchymal stem cells by treating with c(RGDyk). Using cytochalasin D and verteporfin to inhibit polymerization of microfilament and function of nuclear Yes-associated protein (YAP), respectively. For each application, mesenchymal stem cells were loaded by cyclic tensile stress of 10% at 0.5 Hz for 2 h daily. Mesenchymal stem cells were harvested on day 7 post-treatment. Western blotting and quantitative RT-PCR were used to detect the expression of alkaline phosphatase (ALP), RUNX2, ß-actin, integrin αVß3, talin-1, vinculin, FAK, and nuclear YAP. Immunofluorescence staining detected vinculin, actin filaments, and YAP nuclear localization. RESULTS: Cyclic tensile stress could increase the expression of ALP and RUNX2. Inhibition of integrin αVß3 activation led to rearrangement of actin filaments and downregulated the expression of ALP, RUNX2 and promoted YAP nuclear localization. When microfilament polymerization was inhibited, ALP, RUNX2, and nuclear YAP nuclear localization decreased. Inhibition of YAP nuclear localization could reduce the expression of ALP and RUNX2. CONCLUSIONS: Cyclic tensile stress promotes early osteogenesis of human mesenchymal stem cells via the integrin αVß3-actin filaments axis. YAP nuclear localization participates in this process of human mesenchymal stem cells. Video Abstract.

Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors.

BACKGROUND/AIMS: This study explores the relationship between the E3 ubiquitin ligase Ring finger protein 126 (RNF126) and early breast cancer metastasis and tests the hypothesis that RNF126 determines the efficacy of inhibitors targeting Ataxia telangiectasia mutated and Rad3-related kinase (ATR). METHODS: Various metastasis-related genes were identified by univariable Cox proportional hazards regression analysis based on the GSE11121 dataset. The RNF126-related network modules were identified by WGCNA, whereas cell viability, invasion, and migration assays were performed to evaluate the biological characteristics of breast cancer cells with or without RNF126 knockdown. MTT, immunoblotting, immunofluorescence, and DNA fiber assays were conducted to determine the efficiency of ATR inhibitor in cells with or without RNF126 knockdown. RESULTS: RNF126 was associated with early breast cancer metastasis. RNF126 promoted breast cancer cell proliferation, growth, migration, and invasion. ATR inhibitors were more effective at killing breast cancer cells with intact RNF126 due to replication stress compared with the corresponding cells with RNF126 knockdown. Cyclin-dependent kinase 2 (CDK2) was involved in regulating replication stress in breast cancer cells with intact RNF126. CONCLUSION: A high level of expression of RNF126 in early breast cancer patients without lymph node metastases may indicate a high-risk type of metastatic disease, possibly due to RNF126, which may increase breast cancer cell proliferation and invasion. RNF126-expressing breast cancer cells exhibit CDK2-mediated replication stress that makes them potential targets for ATR inhibitors.

Single-cell transcriptomic sequencing analyses of cell heterogeneity during osteogenesis of human adipose-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are known for their multilineage differentiation potential with immune-modulatory properties. The molecular underpinnings of differentiation remain largely undefined. In this study, we investigated the cellular and molecular features of chemically induced osteogenesis from MSC isolated from human adipose tissue (human adipose MSCs, hAMSCs) using single-cell RNA-sequencing (scRNA-seq). We found that a near complete differentiation of osteogenic clusters from hAMSCs under a directional induction. Both groups of cells are heterogeneous, and some of the hAMSCs cells are intrinsically prepared for osteogenesis, while variant OS clusters seems in cooperation with a due division of the general function. We identified a set of genes related to cell stress response highly expressed during the differentiation. We also characterized a series of transitional transcriptional waves throughout the process from hAMSCs to osteoblast and specified the unique gene networks and epigenetic status as key markers of osteogenesis.

Spatial organization and crosstalk of vimentin and actin stress fibers regulate the osteogenic differentiation of human adipose-derived stem cells.

Human adipose-derived stem cells (hASCs) are ideal seed cells for tissue engineering due to their multidirectional differentiation potential. Microfilaments, microtubules, and intermediate filaments are responsible for supporting the intracellular space. Vimentin, a type III intermediate filament protein that is specifically expressed in cells of mesenchymal origin, can function as a scaffold and endow cells with tension and shear stress resistance. Actin stress fibers (ASF) act as an important physical device in stress signal transduction, providing stiffness for cells, and promoting osteogenesis. Through direct physical contact, cross-linkers, and spatial interactions, vimentin and actin networks exist as intersecting entities. Spatial interactions occur in the overlapping area of cytoskeleton subsystems, which could affect cell morphology, cell mechanics, and cell fate. However, how does the spatial organization between the cytoskeletal subsystems changed during osteogenesis, especially between vimentin and ASF, is still not understood, and its mechanism effect on cell fate remains unclear. In our study, WB experiment was used to detect the expression changes in Vimentin, ASF, and other proteins. Cells were reconstructed by three-dimensional scanning with fluorescence microscope, and the spatial thickness of vimentin and ASF cytoskeletons and the thickness of the overlapping area between them were calculated, respectively, so as to observe the spatial reorganization of vimentin and ASF in cells. Cytochalasin D (an inhibitor of actin polymerization) and vimentin upregulated/downregulated cells were used to verify the change in the spatial organization between vimentin and ASF and its influence on osteogenesis. Then, heat shock protein 27 (HSP27) was downregulated to illuminate the regulatory mechanisms of spatial organization between vimentin and ASF during osteogenesis. The amounts and the spatial positions of vimentin and actin stress fiber exhibited opposite trends during osteogenesis. Through controlling the anchor sites on the nucleus, intermediate filaments vimentin can reduce the spatial proportion of actin stress fibers, which can be regulated by HSP27. In addition, depolymerization of actin stress fibers lead to lower osteogenic differentiation ability, resulting in osteogenesis and lipogenesis existed simultaneously, that can be resisted by vimentin. Our data indicate that the spatial reorganization of vimentin and actin stress fibers is a key factor in the regulation of the differentiation state of hASCs. And their spatial overlapping area is detrimental to hASCs osteogenesis, providing a new perspective for further exploring the mechanism underlying hASCs osteogenesis.

Association between Mean Corpuscular Hemoglobin and Platelet Distribution Width Ratio and Knee Osteoarthritis Severity.

BACKGROUND: The goal was to simply and efficiently predict the indicators of disease severity in knee osteoarthritis (KOA) patients. METHODS: One hundred eighty-four patients with KOA and 126 healthy subjects were included. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was used as a reference index for disease severity in KOA patients, in which WOMAC < 80 was classified as mild and WOMAC ≥ 80 as moderate and severe. Blood routine parameters of the KOA and the healthy groups were analyzed by the Mann Whitney U test. Receiver operating characteristic curves were used to analyze the sensitivity and specificity of mean corpuscular hemoglobin and platelet distribution width ratio (MPR) and monocyte and hemoglobin ratio (MHR) indicators. The correlation between MPR and MHR and disease severity of KOA was determined by bivariate regression analysis. Independent predictors of disease severity in patients with KOA were assessed by multivariate regression analysis. RESULTS: MPR, MHR, and WOMAC were significantly higher in the KOA group. The ROC curve indicated that the cutoff values of MPR and MHR were 2.09 and 0.0030, respectively, with sensitivity of 86.4% and 68.5% and specificity of 99.2% and 79.4%. Bivariate regression analysis found that MPR was better correlated with disease severity than MHR. The results of multivariate regression analysis demonstrated that the MPR values of moderate and severe patients were more than 19 times that of mild patients, and the OR values were 21.695 and 19.558, respectively. CONCLUSIONS: MPR and MHR demonstrated a good correlation with disease severity in patients with KOA. MPR is a potential independent predictor of disease severity in patients with KOA.

Actin polymerization state regulates osteogenic differentiation in human adipose-derived stem cells.

BACKGROUND: Actin is an essential cellular protein that assembles into microfilaments and regulates numerous processes such as cell migration, maintenance of cell shape, and material transport. METHODS: In this study, we explored the effect of actin polymerization state on the osteogenic differentiation of human adipose-derived stem cells (hASCs). The hASCs were treated for 7 days with different concentrations (0, 1, 5, 10, 20, and 50 nM) of jasplakinolide (JAS), a reagent that directly polymerizes F-actin. The effects of the actin polymerization state on cell proliferation, apoptosis, migration, and the maturity of focal adhesion-related proteins were assessed. In addition, western blotting and alizarin red staining assays were performed to assess osteogenic differentiation. RESULTS: Cell proliferation and migration in the JAS (0, 1, 5, 10, and 20 nM) groups were higher than in the control group and the JAS (50 nM) group. The FAK, vinculin, paxillin, and talin protein expression levels were highest in the JAS (20 nM) group, while zyxin expression was highest in the JAS (50 nM) group. Western blotting showed that osteogenic differentiation in the JAS (0, 1, 5, 10, 20, and 50 nM) group was enhanced compared with that in the control group, and was strongest in the JAS (50 nM) group. CONCLUSIONS: In summary, our data suggest that the actin polymerization state may promote the osteogenic differentiation of hASCs by regulating the protein expression of focal adhesion-associated proteins in a concentration-dependent manner. Our findings provide valuable information for exploring the mechanism of osteogenic differentiation in hASCs.

Bioinformatics analysis of the biological changes involved in the osteogenic differentiation of human mesenchymal stem cells.

The mechanisms underlying the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) remain unclear. In the present study, we aimed to identify the key biological processes during osteogenic differentiation. To this end, we downloaded three microarray data sets from the Gene Expression Omnibus (GEO) database: GSE12266, GSE18043 and GSE37558. Differentially expressed genes (DEGs) were screened using the limma package, and enrichment analysis was performed. Protein-protein interaction network (PPI) analysis and visualization analysis were performed with STRING and Cytoscape. A total of 240 DEGs were identified, including 147 up-regulated genes and 93 down-regulated genes. Functional enrichment and pathways of the present DEGs include extracellular matrix organization, ossification, cell division, spindle and microtubule. Functional enrichment analysis of 10 hub genes showed that these genes are mainly enriched in microtubule-related biological changes, that is sister chromatid segregation, microtubule cytoskeleton organization involved in mitosis, and spindle microtubule. Moreover, immunofluorescence and Western blotting revealed dramatic quantitative and morphological changes in the microtubules during the osteogenic differentiation of human adipose-derived stem cells. In summary, the present results provide novel insights into the microtubule- and cytoskeleton-related biological process changes, identifying candidates for the further study of osteogenic differentiation of the mesenchymal stem cells.

Environmental physical cues determine the lineage specification of mesenchymal stem cells.

BACKGROUND: Physical cues of cellular environment affect cell fate and differentiation. For example, an environment with high stiffness drives mesenchymal stem cells (MSCs) to undergo osteogenic differentiation, while low stiffness leads to lipogenic differentiation. Such effects could be independent of chemical/biochemical inducers. SCOPE OF REVIEW: Stiffness and/or topography of cellular environment can control MSC differentiation and fate determination. In addition, physical factors such as tension, which resulted from profound cytoskeleton reorganization during MSC differentiation, affect the gene expression essential for the differentiation. Although physical cues control MSC lineage specification probably by reorganizing and tuning cytoskeleton, the full mechanism is largely unclear. It also remains elusive how physical signals are sensed by cells and transformed into biochemical and biological signals. More importantly, it becomes pivotal to define explicitly the physical cue(s) essential for cell differentiation and fate decision. With a focus on MSC, we present herein current understanding of the interplay between i) physical cue and factors and ii) MSC differentiation and fate determination. MAJOR CONCLUSIONS: Biophysical cues can initiate or strengthen the biochemical signaling for MSC fate determination and differentiation. Physical properties of cellular environment direct the structural adaptation and functional coupling of the cells to their environment. GENERAL SIGNIFICANCE: These observations not only open a simple avenue to engineer cell fate in vitro, but also start to reveal the physical elements that regulate and determine cell fate.

Serpin peptidase inhibitor, clade E, member 2 in physiology and pathology: recent advancements.

Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs and secreted by many cell types. The multiple functions of serpin E2 are mainly mediated through regulating urokinase-type plasminogen activator (uPA, also known as PLAU), tissue-type plasminogen activator (tPA, also known as PLAT), and matrix metalloproteinase activity, and include hemostasis, cell adhesion, and promotion of tumor metastasis. The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.

Identification of Biomarkers, Pathways, Immune Properties of Mitophagy Genes, and Prediction Models for Intervertebral Disc Degeneration.

Background: Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD. Methods: Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples. Results: We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group. Conclusion: We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD.

The Visible Human Projects in Korea and China with improved images and diverse applications.

PURPOSE: The Visible Human Projects, which were launched in the United States, have also been developed in Korea and China during the past decade. This article includes the new trials to promote a variety of their applications. METHODS: In a Korean laboratory, whole bodies of two cadavers were serially sectioned (Visible Korean), while two Chinese institutes have sectioned nine cadavers (Chinese Visible Human and Virtual Chinese Human). For acquiring sectioned images and stereoscopic models of better quality, appropriate cadavers were chosen; equipments and techniques for embedding, sectioning, photography, and computer processing were continuously improved in the two countries. To facilitate the research, Korean and Chinese scientists have visited each other. RESULTS: The sectioned images with thinner intervals (0.2 mm or less) and higher resolution were obtained. From the advanced data, the segmented images of comprehensive structures were prepared to construct three-dimensional models. Then, cross-sectional images and models were offered for medical education and clinical practice such as electronic anatomy atlas and virtual lumbar puncture. CONCLUSION: Every project has its strengths and weaknesses with regard to the image data; users in the world can choose the project that best suits their needs.

Astragalus Mongholicus: A review of its anti-fibrosis properties.

Background: Fibrosis-related diseases (FRD) include cerebral fibrosis, pulmonary fibrosis, cardiac fibrosis, liver fibrosis, renal fibrosis, peritoneal fibrosis, etc. The effects of fibrosis can be severe, resulting in organ dysfunction, functional decline, and even organ failure, which can cause serious health problems. Aim: Currently, there is no effective modern medicine for anti-fibrosis in the clinics; however, Chinese medicine has a certain beneficial effect on treating such diseases. Astragalus Mongholicus (AM) has rich medicinal value, and its anti-fibrosis effect has been recently investigated. In recent years, more and more experimental studies have been conducted on the intervention of astragaloside IV (AS-IV), astragalus polysaccharide (APS), astragalus flavone, cycloastragalus alcohol, astragalus water extract and other pharmacological components in fibrosis-related diseases, attracting the interest of researchers. We aim to provide ideas for future research by summarizing recent research advances of AM in treating fibrosis-related diseases. Methods: A literature search was conducted from the core collections of electronic databases such as Baidu Literature, Sciencen.com, Google Scholar, PubMed, and Science Direct using the above keywords and the pharmacological and phytochemical details of the plant. Results: AM can be used to intervene in fibrosis-disease progression by regulating inflammation, oxidative stress, the immune system, and metabolism. Conclusion: AS-IV, APS, and astragalus flavone were studied and discussed in detail. These components have high potential anti-fibrosis activity. Overall, this review aims to gain insight into the AM's role in treating fibro-related diseases.

The role of serum amyloid A1 in the adipogenic differentiation of human adipose-derived stem cells basing on single-cell RNA sequencing analysis.

BACKGROUND: Adipose-derived stem cells (ASCs) are obtained from a variety of sources in vivo where they present in large quantities. These cells are suitable for use in autologous transplantation and the construction of tissue-engineered adipose tissue. Studies have shown that ASCs differentiation is in a high degree of heterogeneity, yet the molecular basis including key regulators of differentiation remains to clarify. METHODS: We performed single-cell RNA sequencing and bioinformatics analysis on both undifferentiated (ASC-GM group) and adipogenically differentiated human ASCs (ASC-AD group, ASCs were cultured in adipogenic inducing medium for 1 week). And then, we verified the results of serum amyloid A1 (SAA1) with western blotting, immunofluorescence staining, oil red O staining. After these experiments, we down-regulated the expression of serum amyloid A1 (SAA1) gene to verify the adipogenic differentiation ability of ASCs. RESULTS: In single-cell RNA sequence analyzing, we obtained 4415 cells in the ASC-GM group and 4634 cells in the ASC-AD group. The integrated sample cells could be divided into 11 subgroups (0-10 cluster). The cells in cluster 0, 2, 5 were came from ASC-GM group and the cells in cluster 1, 3, 7 came from ASC-AD group. The cells of cluster 4 and 6 came from both ASC-GM and ASC-AD groups. Fatty acid binding protein 4, fatty acid binding protein 5, complement factor D, fatty acid desaturase 1, and insulin like growth factor binding protein 5 were high expressed in category 1 and 7. Regulation of inflammatory response is the rank 1 biological processes. And cellular responses to external stimuli, negative regulation of defense response and acute inflammatory response are included in top 20 biological processes. Based on the MCODE results, we found that SAA1, C-C Motif Chemokine Ligand 5 (CCL5), and Annexin A1 (ANXA1) significantly highly expressed during adipogenic differentiation. Western blot and immunofluorescent staining results showed that SAA1 increased during adipogenesis. And the area of ORO positive staining in siSAA1 cells was significantly lower than in the siControl (negative control) cells. CONCLUSIONS: Our results also indicated that our adipogenic induction was successful, and there was great heterogeneity in the adipogenic differentiation of ASCs. SAA1 with the regulation of inflammatory response were involved in adipogenesis of ASCs based on single-cell RNA sequencing analysis. The data obtained will help to elucidate the intrinsic mechanism of heterogeneity in the differentiation process of stem cells, thus, guiding the regulation of self-renewal and differentiation of adult stem cells.

The Mechanism of Ginseng and Astragalus Decoction in the Treatment of Malignant Pleural Effusion Based on Network Pharmacology and Molecular Docking Technology.

Introduction: The objective of our study is to explore the potential active ingredients and activity of Ginseng and Astragalus decoction (GAD) in the treatment of malignant pleural effusion (MPE) by using network pharmacology and molecular docking technologies. Methods: The active ingredients and corresponding targets of Ginseng and Astragalus were extracted from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The relevant targets of malignant pleural effusion (MPE) were searched in the disease databases. Overlapping targets of Ginseng and Astragalus and the corresponding targets of MPE were obtained to define the effective target of GAD for the treatment of MPE. The STRING database was applied to construct a predicted protein-protein interaction network for intersected targets. The Cytoscape software was used to screen key targets with a therapeutic potential. Using the Metascape database, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis on the targets identified in the study. PyMOL and AutoDock Vina were used to molecularly dock the selected key components to their respective key targets for MPE treatment. Results: The core target network revealed 22 main active ingredients, 26 main targets, and 16 signaling pathways in GAD. Molecular docking revealed 6 targets (AKT serine/threonine kinase 1, intercellular adhesion molecule, Jun proto-oncogene, peroxisome proliferator activated receptor gamma, prostaglandin-endoperoxide synthase 2, and tumor necrosis factor) that could partially dock with kaempferol, frutinone A, ginsenoside RH2, formononetin, and quercetin. Conclusions: Several components, targets, and signaling pathways of GAD contribute to the treatment of MPE, which suggests a rationale for further investigation on GAD's active molecule and mechanism of action in the clinical application of MPE.

Anatomic measurement of osseous parameters of the glenoid.

The angle and position of the scapular glenoid are important in shoulder mechanics, the interpretation of diseases, and planning shoulder replacement surgery. In total shoulder replacement, understanding the bony parameters of the glenoid is also of considerable guiding significance for designing implant size and improving material adaptability. To compare glenoid parameters measured from skeletal scapula specimens with those measured by 3D modeling of CT scanning images, analyze correlations between these data, and draw conclusions to guide clinical treatment of shoulder joint injury and total shoulder joint replacement. The data of manual and CT measurements from the same Chinese dry glenoid was compared. Three-dimensional measurement data were collected from the Japanese population and compared with the Chinese population data generated in this study. There were no significant differences between manual measurement and CT measurement in the inclination angle, glenopolar angle, anteroposterior transverse diameter, upper to lower vertical diameter, and depth of the glenoid (P = 0.288, 0.524, 0.111, 0.194, and 0.055, respectively). Further, there were no significant differences between Japanese and Chinese glenoid bones in the upper and lower vertical diameters or anteroposterior transverse diameters (P > 0.05). There were no significant differences between CT and manual measurements, suggesting that the CT method may provide measurements very close to the actual specimen size. This result, however, indicated that the measurer should be careful when measuring the depth of the glenoid.

Review of evidence suggesting that the fascia network could be the anatomical basis for acupoints and meridians in the human body.

The anatomical basis for the concept of meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the evidence supporting a relationship between acupuncture points/meridians and fascia. The reviewed evidence supports the view that the human body's fascia network may be the physical substrate represented by the meridians of TCM. Specifically, this hypothesis is supported by anatomical observations of body scan data demonstrating that the fascia network resembles the theoretical meridian system in salient ways, as well as physiological, histological, and clinical observations. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation.

Cells must alter their expression profiles and morphological characteristics but also reshape the extracellular matrix (ECM) to fulfill their functions throughout their lifespan. Matrix metalloproteinase 3 (MMP-3) is a member of the matrix metalloproteinase (MMP) family, which can degrade multiple ECM components. MMP-3 can activate multiple pro-MMPs and thus initiates the MMP-mediated degradation reactions. In this review, we summarized the function of MMP-3 and discussed its effects on biological activities. From this point of view, we emphasized the positive and negative roles of MMP-3 in the pathogenesis of disease and cell differentiation, highlighting that MMP-3 is especially closely involved in the occurrence and development of osteoarthritis. Then, we discussed some pathways that were shown to regulate MMP-3. By writing this review, we hope to provide new topics of interest for researchers and attract more researchers to investigate MMP-3.

An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer.

Cells and tissues in the human body are subjected to mechanical forces of varying degrees, such as tension or pressure. During tumorigenesis, physical factors, especially mechanical factors, are involved in tumor development. As lung tissue is influenced by movements associated with breathing, it is constantly subjected to cyclical stretching and retraction; therefore, lung cancer cells and lung cancer-associated fibroblasts (CAFs) are constantly exposed to mechanical load. Thus, to better explore the mechanisms involved in lung cancer progression, it is necessary to consider factors involved in cell mechanics, which may provide a more comprehensive analysis of tumorigenesis. The purpose of this review is: 1) to provide an overview of the anatomy and tissue characteristics of the lung and the presence of mechanical stimulation; 2) to summarize the role of mechanical stretching in the progression of lung cancer; and 3) to describe the relationship between mechanical stretching and the lung cancer microenvironment, especially CAFs.

Analysis of differential expression of long non­coding RNAs in exosomes derived from mature and immature dendritic cells.

Dendritic cells release bioactive exosomes involved in immune regulation. Long non­coding RNAs (lncRNAs) are implicated in a number of immunoregulatory mechanisms. However, the roles of lncRNAs in dendritic cell­derived exosomes remain to be elucidated. The present study aimed to investigate the roles of lncRNAs in exosomes derived from mature and immature dendritic cells and to find specific lncRNAs with immunoregulatory function. The expression profiles of lncRNAs in exosomes derived from bone marrow dendritic cells of C57 mice were illustrated. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Gene Set Enrichment Analysis were performed to identify potential targets correlated with immune regulation. In addition, lncRNA­miRNA­mRNA networks were predicted using bioinformatics methods. Representative lncRNAs were further validated via reverse transcription­quantitative PCR. A total of 437 lncRNAs were analyzed using RNA­seq. Among these, the expression of ~87 lncRNAs was upregulated and 21 lncRNAs was downregulated in mature dendritic cell­derived exosomes (Dex) compared with immature Dex. GO analyses indicated the involvement of upregulated lncRNAs in multiple biological functions, such as the immune system process, while downregulated lncRNAs were involved in poly(A) RNA binding. Analysis of the KEGG pathway identified the relationship of TNF signaling and ribosome pathway with upregulated lncRNAs and downregulated lncRNAs, respectively. The results of gene set enrichment analysis identified that three lncRNA­associated transcripts (Procr­203, Clec4e­202 and Traf1­203) were highly associated with immunoregulatory functions including T helper cell differentiation and Janus kinase­STAT signaling pathway. The results indicated the involvement of candidate lncRNAs in immunoregulation and suggested a new perspective on the modulation of lncRNAs in Dex.