MMP-1 and MMP-9 are Highly Expressed in the Joint Capsule of Diabetic Frozen Shoulder.

BACKGROUND: The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that lead capsular fibrosis. However, there has been little concern for why diabetic FS has more protracted fibrotic condition. The objective of this study was to compare the expression levels of MMPs and TIMPs in the joint capsule of patients with diabetic and non-diabetic FS. MATERIALS AND METHODS: Samples of capsular tissue were collected from 20 patients with FS (10 diabetic patients; diabetic group, and 10 non-diabetic patients; non-diabetic group) and 10 patients (control group) with chronic anterior shoulder instability. Quantitative real-time RT-PCR and Western blot analysis were performed to determine the expression levels of mRNA and protein for MMP-1, 3, 9, 13, 14, and TIMP-1, 2. RESULTS: The results of quantitative real-time RT-PCR showed significantly higher expression levels of all MMPs and TIMP-1 and significantly lower expression levels of TIMP-2 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. Significantly higher expression levels of MMP-1, 9, 14, and TIMP-1 were detected in the diabetic group compared with the non-diabetic group. The results of Western blot analysis showed significantly higher levels of MMP-3, 13, 14, and TIMP-1 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. However, no significant differences of protein levels of them were observed between diabetic and non-diabetic groups. CONCLUSIONS: The findings of this study demonstrate the potential involvement of MMP-1 and 9 in the pathophysiology of diabetic FS. These findings may be helpful in identification of therapeutic targets for development of novel treatments for this protracted chronic fibrosing condition.

Creative Intercorporeality in Collaborative Work of Choreographers with and without Disabilities: A Grounded Theory Approach.

The purpose of this study was to present an academic discourse on a theoretical framework and acceptance process of 'creative intercorporeality' in the collaborative work of choreographers with and without disabilities. To this end, a grounded theory approach using a qualitative research method was employed to dancers who have participated in collaborative choreography. This study employed the perspective of social cognitive theory about the process in which dancers with and without disabilities form emotional empathy and trust relationships through continuous interactions for creative work. Physical, emotional, cognitive, and behavioral empathy and interactions in the collaborative work of choreographers with and without disabilities were discussed as a process of forming 'creative intercorporeality' that is defined as creative attitude and perspective consisting of harmony, concurrency, consistency, and balance.

OTT Streaming Distribution Strategies for Dance Performances in the Post-COVID-19 Age: A Modified Importance-Performance Analysis.

The purpose of this study was to explore strategies for distributing online content of dance post COVID-19 in Korea. And specially to discuss the distribution strategies of online performances through videoization of dance performances and OTT (over-the-top) streaming: (1) Methods: For this purpose, a survey was conducted on the distribution strategy of dance online contents for a total of 100 practitioners such as dance field, video contents, and art management. A total 91 sample were used except for defective questionnaires, and Vavra (1997)'s modified important performance analysis was conducted; (2) Results: The results of the matrix through the modified IPA analysis are as follows: first, the first quadrant included 'quality of dance performance', 'platform for OTT streaming', and 'promotion for potential audience development'. This means that both explicit and intrinsic importance are high, and it is an important execution factor that has a positive effect on the satisfaction of the online contents of dance only if it is met. Second, the second quadrant included 'brand awareness of choreographer or dance company', 'creative composition and choreography', and 'fee and price criteria'. This is a case of low explicit importance but high intrinsic importance, and these factors are attractive attributes that affect the satisfaction of dance online contents, although consumers do not expect it to be important. Third, the third quadrant included 'new formats and curation', 'convergence technology (AR, VR, 3D, etc.) for the field sense', and 'online audience service (communication, membership, etc.)'. This means that both explicit and intrinsic importance are low, and if these factors are met, it can have a positive effect on the satisfaction of viewing of dance online contents. However, it does not have a negative effect even if it is not met. Fourth, in the fourth quadrant, 'production and editing competency', 'quality of videos and sounds', 'copyright of performance creation', and 'fandom and audience management' was included. This is an essential attribute in the distribution strategy of dance online contents because it has high explicit importance and low intrinsic importance, and it can have a negative impact on satisfaction when these factors are not met.

Enhancement of aberrantly modified integrin­mediated cell motility in multicellular tumor spheroids.

Multicellular tumor spheroids (MTSs) of malignant cells can display cell­cell and cell­matrix interactions, different from monolayer cultures. The objective of the present study was to examine difference in intercellular and cell­matrix interaction between monolayered cultures and spheroid cultures. Expression levels of cell adhesion molecules (CAMs) and epithelial­mesenchymal transition (EMT) signaling molecules in monolayered cells and MTS cells were compared. The motility of single cells dispersed from each culture was evaluated using a live­cell imaging device. The effect of an E­cadherin neutralizing antibody, DECMA, was also compared between the two cultures. Among various CAMs, only E­cadherin was increased in MTSs. The motility of single cells dispersed from MTSs was higher than that from monolayered cells. Compared with monolayered cells, the molecular weight (MW) of ß1 integrin was decreased during MTS formation, particularly during the early stage. This notable reduction was maintained when DECMA was used to treat MTSs. Additionally, the expression levels of the EMT signaling molecules Snail and ILK increased more in MTSs than in monolayered cells. The blocking of E­cadherin elicited increased expression levels of EMT molecules and cellular motility only in MTSs. In conclusion, the alteration of E­cadherin expression and presence of low­MW ß1 integrin in MTS may enhance cell motility via the upregulation of EMT signaling molecules that may be intensified by blocking E­cadherin.

Penta-1,2,3,4,6-O-Galloyl-ß-D-Glucose Inhibits UVB-Induced Photoaging by Targeting PAK1 and JNK1.

Penta-O-galloyl-ß-D-glucose (PGG) is a gallotannin polyphenolic compound that occurs naturally in fermented Rhus verniciflua. The present study aimed to examine the effect of PGG on UVB-induced skin aging and its molecular mechanisms in HaCaT human keratinocytes and SKH-1 hairless mice models. PGG suppressed UVB-induced matrix metalloproteinase-1 (MMP-1) expression in HaCaT cells by inhibiting phosphorylation of RAF/MEK/ERK, MKK3/6/p38, and c-Jun. UVB-induced ERK and p38 signaling pathways that induce the MMP-1 expression were mediated by PAK1 in HaCaT cells. PGG suppressed PAK1 and JNK1 kinase activities, and directly bound both PAK1 in an ATP-competitive manner and JNK1 in an ATP-noncompetitive manner. Consistently, PGG decreased UVB-induced wrinkle formation, epidermal thickness, type 1 collagen and MMP-13 expression in mouse skin. Overall, these results indicate that PGG exhibits anti-photoaging effects in vitro and in vivo by the suppression of PAK1 and JNK1 kinase activities, and may be useful for the prevention of skin aging.

Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells.

Cleavage of E-cadherin and the resultant weakness in the cell-cell links in the laryngeal epithelium lining is induced by exposure to acidic contents of the refluxate. Herein, we aimed to evaluate the role of matrix metalloproteinases (MMPs) in inducing E-cadherin level changes following acid exposure to the human pharyngeal mucosal cells. E-cadherin levels were inversely correlated with the duration of acid exposure. Treatment with actinonin, a broad MMP inhibitor, inhibited this change. Immunocytochemical staining and transepithelial permeability test revealed that the cell surface staining of E-cadherin decreased and transepithelial permeability increased after acid exposure, which was significantly inhibited by the MMP inhibitor. Among the various MMPs analyzed, the mRNA for MMP-7 in the cellular component was upregulated, and the secretion and enzymatic activity of MMP-7 in the culture media increased with the acid treatment. Consequently, MMP-7 plays a significant role in the degradation of E-cadherin after exposure to a relatively weak acidic condition that would be similar to the physiologic condition that occurs in Laryngopharyngeal reflux disease patients.

Budget Impact of Switching to Biosimilar Trastuzumab (CT-P6) for the Treatment of Breast Cancer and Gastric Cancer in 28 European Countries.

BACKGROUND: As the economic burden of treating cancer patients has been soaring in European countries, performing a budget impact analysis is becoming one of the requirements for payers' application dossiers. OBJECTIVE: The objective of this study was to estimate the budgetary impact of introducing the biosimilar trastuzumab (CT-P6) from the payer's perspective and to determine the number of additional patients who could be treated with resulting savings in 28 European countries. METHODS: A budget impact model was developed to analyze the financial impact of switching from originator trastuzumab to biosimilar CT-P6 in the treatment of early and metastatic breast cancer and metastatic gastric cancer with a time horizon of 1-5 years. Budgetary savings and the number of patients potentially affected were measured based on epidemiological and sales volume data. The base-case analysis assumed that the price of CT-P6 is 70% of the originator price, the switching rate of originator to CT-P6 in the first year is 20%, and the annual growth in the switching rate for each subsequent year is 5%. RESULTS: For analyses using the base-case scenario following CT-P6 introduction, the total estimated budgetary savings over a 5-year period (depending on the scenario) ranged from €1.13 billion to €2.27 billion based on epidemiological data, or from €0.91 billion to €1.82 billion based on sales volume data. In the first year only, the projected budgetary savings ranged from €58 million to €136 million, and the number of additional patients who could be treated using the savings ranged from 3503 to 7078 by sensitivity analysis. CONCLUSIONS: The conducted budget impact analysis assessing a switch from originator trastuzumab to biosimilar CT-P6 in 28 European countries indicates that budget savings could be between €0.91 billion and €2.27 billion over the next 5 years. These savings could be used to help improve patient access to local biologics in their respective countries while simultaneously strengthening the overall public health landscape across the European Union.