Circ_0005736 promotes tenogenic differentiation of tendon-derived stem cells through the miR-636/MAPK1 axis.

BACKGROUND: Tendon-derived stem cells (TDSCs) are one of stem cells characterized by greater clonogenicity, tenogenesis, and proliferation capacity. Circ_0005736 has been shown to be decreased in Rotator cuff tendinopathy. Here, we investigated the function and relationship of circ_0005736 in TDSC tenogenic differentiation. METHODS: Transforming growth factor ß1 (TGF-ß1) was used to induce the tenogenic differentiation in TDSC. Cell proliferation, invasion and migration were evaluated by Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine, transwell, and wound healing assays, respectively. The detection of the levels of genes and proteins was performed by qRT-PCR and Western blot. The binding between miR-636 and circ_0005736 or MAPK1 (Mitogen-Activated Protein Kinase 1) was verified using dual-luciferase reporter assay and RIP assays. RESULTS: TGF-ß1 induced tenogenic differentiation by enhancing the production of tendon-specific markers and TDSC proliferation, invasion and migration. TGF-ß1 treatment promoted circ_0005736 expression, knockdown of circ_0005736 abolished TGF-ß1-induced tenogenic differentiation in TDSCs. Mechanistically, circ_0005736 acted as a sponge for miR-636 to up-regulate the expression of MAPK1, which was confirmed to be a target of miR-636 in TDSCs. Further rescue assays showed that inhibition of miR-636 could rescue circ_0005736 knockdown-induced suppression on TGF-ß1-caused tenogenic differentiation in TDSCs. Moreover, forced expression of miR-636 abolished TGF-ß1-caused tenogenic differentiation in TDSCs, which was rescued by MAPK1 up-regulation. CONCLUSION: Circ_0005736 enhanced TGF-ß1-induced tenogenic differentiation in TDSCs via increasing the production of tendon-specific markers and TDSC proliferation, invasion and migration through miR-636/MAPK1 axis.

Circular circRANGAP1 Contributes to Non-small Cell Lung Cancer Progression by Increasing COL11A1 Expression Through Sponging miR-653-5p.

Numerous studies have discovered that hsa_circ_0063526 (also known as circRANGAP1) is an oncogenic circular RNA (circRNA) in some human tumors, including non-small cell lung cancer (NSCLC). However, the concrete molecular mechanism of circRANGAP1 involved in NSCLC is not completely elucidated. CircRANGAP1, microRNA-653-5p (miR-653-5p), and Type XI collagen (COL11A1) contents were determined via real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, migration, and invasion were measured using 5-ethynyl-2'-deoxyuridine (EdU), colony formation, wound healing, and transwell assays. E-cadherin, N-cadherin, Vimentin, and COL11A1 protein levels were detected via western blot assay. After Starbase software prediction, the binding between miR-653-5p and circRANGAP1 or COL11A1 was verified using a dual-luciferase reporter assay. Besides, the role of circRANGAP1 on tumor cell growth was analyzed using a xenograft tumor model in vivo. Increased circRANGAP1 and COL11A1, and reduced miR-653-5p were found in NSCLC tissues and cell lines. Furthermore, circRANGAP1 absence might hinder NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Mechanically, circRANGAP1 functioned as a sponge of miR-653-5p to increase COL11A1 expression. In vivo experiments illustrated that circRANGAP1 knockdown repressed tumor growth. CircRANGAP1 silencing might suppress NSCLC cell malignant biological behaviors, at least in part, through the miR-653-5p/COL11A1 axis. These results provided a promising strategy for treating NSCLC malignancies.

Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis.

Melatonin is a well-known anti-inflammatory and antioxidant molecule, which plays a crucial role in various physiological functions. In this study, mice received a single dose of 15 Gy radiation delivered to the lungs and daily intraperitoneal administration of melatonin. After 7 days, mice were processed to harvest either bronchoalveolar lavage fluid for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that melatonin markedly alleviated the oxidative stress and injury, especially suppressing the infiltration of macrophages (CD11b+CD11c-) and neutrophils (CD11b+Ly6G+) to the irradiated lungs. Moreover, in the irradiated RAW 264.7 cells, melatonin blocked the NLRP3 inflammasome activation accompanied with the inhibition of the IL-1ß release and caspase-1 activity. However, melatonin restored the downregulated miR-30e levels. Quantitative PCR analysis of miR-30e and NLRP3 indicated the negative correlation between them. Notably, immunofluorescence staining showed that overexpression of miR-30e dramatically diminished the increased NLRP3 expression. Luciferase reporter assay confirmed that NLRP3 was a target gene of miR-30e. Western blotting revealed that transfection with miR-30e mimics markedly reduced the expressions of NLRP3 and cleaved caspase-1, whereas this phenomenon was reversed by the miR-30e inhibitor. Consistent with this, the beneficial effect of melatonin under irradiated exposure was blunted in cells transfected with anti-miR-30e. Collectively, our results demonstrate that the NLRP3 inflammasome contributed to the pathogenesis of radiation-induced lung injury. Meanwhile, melatonin exerted its protective effect through negatively regulating the NLRP3 inflammasome in macrophages. The melatonin-mediated miR-30e/NLRP3 signaling may provide novel therapeutic targets for radiation-induced injury.

Ultrafast PM fiber ring laser mode-locked by nonlinear polarization evolution with short NPE section segments.

We demonstrate a nonlinear polarization evolution (NPE) mode-locked polarization maintaining (PM) Yb-doped fiber laser with short NPE section segments by setting proper splicing angle. With a theoretical analysis, we propose that an appropriate deviation splicing angle exists to maximize the adjustable range of transmission modulation. The simulation results are highly consistent with theoretical conclusions. Experimentally, using the optimal splicing angle predicted by the theoretical calculation, we have achieved an environmentally stable mode-locking fiber laser at 111-MHz repetition rate with corresponding pulse energy of 0.47 nJ. Additionally, the noise performance of this PM fiber laser is characterized. The measured RMS timing jitter and amplitude noise are 6.41 fs and 0.0052% respectively (1 kHz-10 MHz), which are competitive to the low phase noise performance of the typical fiber laser.

Programmable controlled mode-locked fiber laser using a digital micromirror device.

A digital micromirror device (DMD)-based arbitrary spectrum amplitude shaper is incorporated into a large-mode-area photonic crystal fiber laser cavity. The shaper acts as an in-cavity programmable filter and provides large tunable dispersion from normal to anomalous. As a result, mode-locking is achieved in different dispersion regimes with watt-level high output power. By programming different filter profiles on the DMD, the laser generates femtosecond pulse with a tunable central wavelength and controllable bandwidth. Under conditions of suitable cavity dispersion and pump power, design-shaped spectra are directly obtained by varying the amplitude transfer function of the filter. The results show the versatility of the DMD-based in-cavity filter for flexible control of the pulse dynamics in a mode-locked fiber laser.

Depletion of circulating monocytes suppresses IL-17 and HMGB1 expression in mice with LPS-induced acute lung injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an important cause of mortality in critically ill patients. Macrophages play an important role in the pathogenesis of ALI/ARDS. To investigate the role and underlying mechanisms of circulating monocytes and resident alveolar macrophages (AMs) in ALI/ARDS, we depleted circulating monocytes and AMs by clodronate-loaded liposome (CL) in a lipopolysaccharide (LPS)-induced ALI/ARDS mouse model. Our results indicated that depletion of circulating monocytes by intravenous injection of CL 2 days before intratracheal LPS treatment significantly suppressed the acute lung injury in mice with ALI/ARDS, accompanied with significant reduction in neutrophil influx, interleukin-17, monocyte chemoattractant protein 1, high-mobility group box 1 protein, suppressor of cytokine signaling 3, and surfactant protein D (SP-D) in the lungs of 2 days intratracheal LPS-treated mice. In contrast, depletion of AMs by intratracheal delivery of CL enhanced the acute lung injury in association with upregulation of these mediators. Blocking monocyte chemoattractant protein 1 signaling by intraperitoneal instillation of anti-mouse CCL2 neutralizing antibody significantly reduced acute lung injury and neutrophil influx. In addition, SP-D was upregulated by mediators released from AMs because primary murine type II alveolar epithelial cells expressed more SP-D after treatment with bronchoalveolar lavage from LPS-treated mice or the conditioned media from LPS-treated RAW 264.7 cells. The results indicated that circulating monocytes are proinflammatory, but AMs have anti-inflammatory functions in the early phase of ALI/ARDS. The study provided a molecular basis for the treatment of ALI/ARDS through modulation of circulating monocytes and AMs.