Aerodynamic Simulation of Small Airway Resistance: A New Imaging Biomarker for Chronic Obstructive Pulmonary Disease.

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.

New Perspectives on the Role and Therapeutic Potential of Melatonin in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. It is essential to develop novel interventions to prevent/delay CVDs by targeting their fundamental cellular and molecular processes. Melatonin is a small indole molecule acting both as a hormone of the pineal gland and as a local regulator molecule in various tissues. It has multiple features that may contribute to its cardiovascular protection. Moreover, melatonin enters all cells and subcellular compartments and crosses morphophysiological barriers. Additionally, this indoleamine also serves as a safe exogenous therapeutic agent. Increasing evidence has demonstrated the beneficial effects of melatonin in preventing and improving cardiovascular risk factors. Exogenous administration of melatonin, as a result of its antioxidant and anti-inflammatory properties, has been reported to decrease blood pressure, protect against atherosclerosis, attenuate molecular and cellular damage resulting from cardiac ischemia/reperfusion, and improve the prognosis of myocardial infarction and heart failure. This review aims to summarize the beneficial effects of melatonin against these conditions, the possible protective mechanisms of melatonin, and its potential clinical applicability in CVDs.

Monocyte chemoattractant protein­1 promotes the proliferation, migration and differentiation potential of fibroblast­like synoviocytes via the PI3K/P38 cellular signaling pathway.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and joint destruction. Monocyte chemoattractant protein 1 (MCP­1) is highly expressed in the joints of patients suffering from RA. The present study aimed to evaluate the effects of MCP­1 on the phenotype of fibroblast­like synoviocytes (FLSs) and their differentiation potential towards vascular endothelial cells. The expression of MCP­1 in collagen­induced arthritis (CIA) rats was investigated by PCR, ELISA and immunohistology. Cell proliferation induced by MCP­1 was measured using a Cell Counting Kit­8 (CCK­8) and 5­Bromo­2­deoxyuridine ELISA assay. In addition, the effects of MCP­1 on the migration of FLSs was examined using a Transwell assay. Activation of PI3K and P38 were investigated by western blotting following MCP­1 treatment. The vascular endothelial cell markers, tumor necrosis factor alpha (TNF­α) and interleukin­1 beta (IL­ß), were also examined by western blotting. LY294002 [PI3K inhibitor, (LY)] and SB203580 [P38 inhibitor, (SB)] were used to examine the proliferative and pro­differentiation effect of PI3K and P38. The present findings showed that the expression level of MCP­1 in the synovium of CIA rats was significantly higher compared with controls. The present in vitro study suggested that MCP­1 increased the FLSs cell numbers with a maximal effect at 200 ng/ml, and induced the maximal phosphorylation of PI3K at 15 min and P38 at 30 min. In addition, MCP­1 stimulation significantly increased the migration of FLSs. Furthermore, MCP­1­induced the expression of vascular endothelial growth factor and CD31 in FLSs. Suppression of PI3K and P38 was found to reduce MCP­1 induced FLSs proliferation and migration, and decreased the expression levels of angiogenesis markers increased following MCP­1 treatment. MCP­1 was also found to increase the expression levels of both TNF­α and IL­ß. Therefore, MCP­1 could promote the proliferation and migration of FLSs, and was found to increase the expression levels of various angiogenesis markers via PI3K/P38, suggesting a role for this pathway in synovium hyperplasia in RA.