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Timely differentiation of monocytes into M2-like macrophages is important in the cardiac healing process after myocardial infarction (MI), but molecular mechanisms governing M2-like macrophage differentiation at the transcriptional level after MI have not been fully understood.Methods and ResultsA time-series microarray analysis of mRNAs and microRNAs in macrophages isolated from the infarcted myocardium was performed to identify the microRNAs involved in regulating the process of differentiation to M2-like macrophages. Correlation analysis revealed 7 microRNAs showing negative correlations with the progression of polarity changes towards M2-like subsets. Next, correlation coefficients for the changes in expression of mRNAs and miRNAs over time were calculated for all combinations. As a result, miR-27a-5p was extracted as a possible regulator of the largest number of genes in the pathway for the M2-like polarization. By selecting mouse mRNAs and human mRNAs possessing target sequences of miR-27a-5p and showing expression patterns inversely correlated with that of miR-27a-5p, 8 potential targets of miR-27a-5p were identified, includingPpm1l. Using the mouse bone marrow-derived macrophages undergoing differentiation into M2-like subsets by interleukin 4 stimulation, we confirmed that miR-27a-5p suppressed M2-related genes by negatively regulatingPpm1lexpression.

Ppm1land miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation ofPpm1lexpression.

Ppm1land miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation ofPpm1lexpression.

It is recommended to remove retrievable inferior vena cava filters (r-IVCFs) when they are no longer needed because their presence may give rise to serious complications related to prolonged placement of the filter. An advanced filter retrieval technique may help improve the retrieval rate.Methods and Results107 consecutive patients (mean age; 61±18 years, male 53%) in whom r-IVCF retrieval was attempted were prospectively enrolled between April 2012 and December 2018. The frequently used advanced techniques were sling technique and biopsy forceps dissection technique. Retrieval success was 75% with standard retrieval technique alone; however, the overall retrieval success rate improved to 98% with advanced techniques. We observed few serious complications related to the retrieval procedure. Logistic multivariate analysis identified prolonged indwelling time (P=0.0011) and embedded hook in the caval wall (P=0.0114) as independent predictors, and the cutoff value for the indwelling time for requirement of advanced technique was 80 days.

Advanced retrieval techniques helped improve the retrieval rate without serious complications. We may need to consider the referral of patients to centers with expertise in advanced retrieval techniques when the indwelling time is >80 days, and pre-retrieval CT image shows a hook embedded in the vessel wall.

80 days, and pre-retrieval CT image shows a hook embedded in the vessel wall.

Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease.

In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. XST14 To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis.

There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR ( p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018).

Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.

Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.Radiation is an effective cancer treatment, but cancer cells can acquire radioresistance, which is associated with increased DNA damage response and enhanced proliferative capacity, and therefore, it is important to understand the intracellular biochemical responses to γ-irradiation. The transient receptor potential melastatin 8 (TRPM8) channel plays roles in the development and progression of tumors, but it is unclear whether it is involved in the DNA damage response induced by γ-irradiation. Here, we show that a TRPM8 channel inhibitor suppresses the DNA damage response (phosphorylated histone variant H2AX-p53-binding protein 1 (γH2AX-53BP1) focus formation) and colony formation of B16 melanoma cells. Furthermore, the TRPM8 channel-specific agonist WS-12 enhanced the DNA damage response and increased the survival fraction after γ-irradiation. We found that the TRPM8 channel inhibitor enhanced G2/M phase arrest after γ-irradiation. Phosphorylation of ataxia telangiectasia mutated and p53, which both contribute to the DNA damage response was also suppressed after γ-irradiation.