Post-treatment with Resolvin D1 attenuates pulmonary hypertension by inhibiting endothelial-to-mesenchymal transition.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is an important manifestation and mechanism of pulmonary vascular remodeling. Resolvin D1 (RvD1) is an endogenous lipid mediator promoting the resolution of inflammation. However, the role of RvD1 on EndMT in PH remains unknown. Here, we aimed to investigate the effect and mechanisms of RvD1 on the treatment of PH. We showed that RvD1 and its receptor FPR2 expression were markedly decreased in PH patients and both chronic hypoxia-induced PH (CH-PH) and sugen 5416/hypoxia-induced PH (SuHx-PH) mice models. RvD1 treatment decreased right ventricular systolic pressure (RVSP) and alleviated right ventricular function, and reduced pulmonary vascular remodeling and collagen deposition in the perivascular of both two PH mice models. Then, RvD1 inhibited EndMT in both the lungs of PH mice models and primary cultured human umbilical vein endothelial cells (HUVECs) treated with TGF-ß and IL-1ß. Moreover, RvD1 inhibited EndMT by downregulating Smad2/3 phosphorylation in vivo and in vitro via FPR2. In conclusion, our date suggest that RvD1/FPR2 axis prevent experimental PH by inhibiting endothelial-mensenchymal-transition and may be a therapeutic target for PH.

Nerve-on-a-Chip Derived Biomimicking Microfibers for Peripheral Nerve Regeneration.

Fibrous scaffolds have shown their advantages in tissue engineering, such as peripheral nerve regeneration, while most of the existing fiber-shaped scaffolds are with simple structures, and the in vitro performance for nerve regeneration lacks systematic analysis. Here, novel nerve-on-a-chip derived biomimicking microfibers for peripheral nerve regeneration are presented. The microfibers with controllable core-shell structures and functionalities are generated through capillary microfluidic devices. By integrating these microfibers into a multitrack-architectured chip, and coculturing them with nerve cells as well as gradient bioactive elements, the nerve-on-a-chip with the capabilities of systematically assessing the performances of nerve fiber formation in the hollow microfibers at in vitro level is constructed. Based on a rat sciatic nerve injury model, the rapid promotion ability is demonstrated of optimized microfibers in nerve regeneration and function recovery in vivo, which implies the credibility of the nerve-on-a-chip on biomimicking microfibers evaluation for peripheral nerve regeneration. Thus, it is convinced that the organ-on-a-chip will undoubtedly open up a new chapter in evaluating biological scaffolds for in vivo tissue engineering.

Combining a Density Gradient of Biomacromolecular Nanoparticles with Biological Effectors in an Electrospun Fiber-Based Nerve Guidance Conduit to Promote Peripheral Nerve Repair.

Peripheral nerve injury is a serious medical problem with limited surgical and clinical treatment options. It is of great significance to integrate multiple guidance cues in one platform of nerve guidance conduits (NGCs) to promote axonal elongation and functional recovery. Here, a multi-functional NGC is constructed to promote nerve regeneration by combining ordered topological structure, density gradient of biomacromolecular nanoparticles, and controlled delivery of biological effectors to provide the topographical, haptotactic, and biological cues, respectively. On the surface of aligned polycaprolactone nanofibers, a density gradient of bioactive nanoparticles capable of delivering recombinant human acidic fibroblast growth factor is deposited. On the graded scaffold, the proliferation of Schwann cells is promoted, and the directional extension of neurites from both PC12 cells and dorsal root ganglions is improved in the direction of increasing particle density. After being implanted in vivo for 6 and 12 weeks to repair a 10-mm rat sciatic nerve defect, the NGC promotes axonal elongation and remyelination, achieving the regeneration of the nerve not only in anatomical structure but also in functional recovery. Taken together, the NGC provides a favorable microenvironment for peripheral nerve regeneration and holds great promise for realizing nerve repair with an efficacy close to autograft.

Insight into nitrogen and phosphorus coupling effects on mixotrophic Chlorella vulgaris growth under stably controlled nutrient conditions.

In water environment, nitrogen (N) and phosphorus (P) are biochemically dependent nutrients following the co-limitation concept for algae growth under mixotrophic mode. From a practical viewpoint, algae growth may not bring about significant change of the background nutrient concentration of an actual waterbody in contrast to a conventional batch system. In order to better understand the growth pattern of microalgae in aquatic environments, a series of experiments were conducted under stably controlled N-P levels for studying the N-P coupling effect on mixotrophic Chlorella vulgaris growth process, with attention paid to the physiological and biochemical characteristics. It was found that within the concentration range of N = 1-8 mg·L-1 and P = 0.1-1.0 mg·L-1, the variation of the N-P level slightly affected the specific growth rate, but significantly influenced nutrients uptake, biomass dry weight, chlorophyll contents of the grown C. vulgaris. The biochemical and elemental composition of the microalgae tended to be more sensitive to the N-P concentrations and ratios in the lower nutrient range (1-2 mg N·L-1, 0.1-0.4 mg P·L-1) in which the highest N and P conversion rates were gained as 90.18 ± 1.23% and 60.47 ± 1.59%, respectively. The P assimilation and conversion efficiencies were much affected by both N and P supplies, while the P supply showed little influence on N assimilation and conversion efficiencies. It was also noticed that the N level greatly affected the metabolic pathway involving nutrient assimilation, carbohydrate fixation and monosaccharide profile, resulting in conversion of the dominant fraction of protein at N ≤ 2 mg·L-1 into other biochemical compositions including lipids at N ≥ 3 mg·L-1. The fatty acid methyl esters (FAMEs) composition tended to differ with varied nutrient levels. These findings may deepen our understanding of algal growth in aquatic environment and provide perspective for eutrophication control.