Low-temperature additive manufacturing (AM) holds promise for fabrication of three-dimensional (3D) scaffolds containing bioactive molecules and/or drugs. Due to the strict technical limitations of current approaches, few materials are suitable for printing at low temperature. Here, a low-temperature robocasting method was employed to print biomimic 3D scaffolds for bone regeneration using a routine collagen-hydroxyapatite (CHA) composite material, which is too viscous to be printed via normal 3D printing methods at low temperature. The CHA scaffolds had excellent 3D structure and maintained most raw material properties after printing. Compared to nonprinted scaffolds, printed scaffolds promoted bone marrow stromal cell proliferation and improved osteogenic outcome in vitro. In a rabbit femoral condyle defect model, the interconnecting pores within the printed scaffolds facilitated cell penetration and mineralization before the scaffolds degraded and enhanced repair, compared to nonprinted CHA scaffolds. Additionally, the optimal printing parameters for 3D CHA scaffolds were investigated; 600-μm-diameter rods were optimal in terms of moderate mechanical strength and better repair outcome in vivo. This low-temperature robocasting method could enable a variety of bioactive molecules to be incorporated into printed CHA materials and provides a method of bioprinting biomaterials without compromising their natural properties.

Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders.Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS.Results: Our data revealed following interesting findings: (1) LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2) LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells), MSCs (mesenchymal stem cells), B1-B cells and Treg (regulatory T cells); (3) LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4) LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5) Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6) LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways.Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair.

The decidedly interesting observation of the reaction of the chromium-carbene complex 1 with diphenylacetylene appeared in the literature in 1975.' This cyclization reaction occurs with incorporation of the acetylene and a carbon monoxide ligand to give the (naphthol)chromium tricarbonyl complex 2. We anticipate that this reaction will be synthetically valuable and are currently utilizing it in the synthesis of anthracyclines. We report here our results concerning the regiochemistry of this reaction and its extension to several carbene complexes bearing certain aryl substituents.1 2

Aim: The aims of this study are to investigate the effects of neurotransmitters NPY and CGRP on ERK signaling in fracture healing, and to identify the correlation between macrophage aggregation and fracture healing. Methods: Male Sprague-Dawley rats were used to build a fracture model. The neurotransmitter receptor inhibitors were injected intraperitoneally into the rats. Immunofluorescence staining and ELISA were employed to determine the expression of NPY and CGRP in fracture area and the peripheral blood, respectively. Micro-CT together with histological staining were utilized to assess the fracture healing conditions. Relative protein expression was determined using western blot. Immunofluorescence staining was used to detect the aggregation of macrophages in the injury area. Results: During fracture healing, the serum NPY and CGRP significantly increased. The levels of NPY and CGRP reached a peak in the 8^th week and reduced significantly thereafter. NPY and CGRP inhibitors could inhibit fracture healing and down-regulate the phosphorylated ERK. Macrophages (NPY+ and CGRP+) aggregated in the injury area. Conclusion: NPY and CGRP participated in fracture healing, in which they were also shown to influence phosphorylated ERK expression. In addition, macrophages are involved in the fracture healing process.

Full details of three approaches to an entirely regio- and stereoselective synthesis of the well-known target reserpine are described, culminating in a total synthesis which efficiently meets these requirements.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases which play key roles in extracellular matrix remodeling, connective tissue damage, inflammation and cell proliferation in a variety of tissues. Since MMP inhibitors have been recently shown to decrease proliferation of vascular smooth-muscle cells, and to prevent neutrophil infiltration in response to alkali burns, we sought to determine whether MMPs play a role in the pathogenesis of inflammatory or hyperproliferative skin disorders. The effects of a specific MMP inhibitor and its analogues on phorbol dibutyrate (PdiBu)-induced inflammation and epidermal hyperplasia in murine skin were assessed. Topical GM 6001, a hydroxamic acid analog with potent inhibitory activity against several MMPs, markedly inhibited PdiBu-induced increases in both ear thickness and ear punch-biopsy weight in a dose-dependent manner 30 h after topical application of PdiBu. Maximal inhibition (75%) was obtained at a dose of 100 micrograms/cm2 (P < 0.01). Moreover, histologic analysis revealed that GM 6001 decreased both the inflammatory cellular infiltrates and epidermal hyperplasia induced by PdiBu. Whereas similar results were found for GM 1489, an analog of GM 6001, acetohydroxamic acid, containing the critical metal ligand group but without the amino acid side chains necessary for binding to the MMPs, did not alter the response to PdiBu inflammation/hyperplasia. These results show that the MMP inhibitors, GM 6001 and GM 1489, are effective in reducing both the inflammatory and hyperproliferative responses that occur following topical phorbol ester application, suggesting a potential role for MMPs in cutaneous inflammatory dermatoses. Moreover, the delivery of this class of inhibitors across intact stratum corneum implies that MMP inhibition could provide an approach to the topical treatment of inflammatory dermatoses.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. It is possible that some strains present in the natural environment possess a higher tolerance to inorganic iron and a higher ability to convert and accumulate iron compared with Saccharomyces cerevisiae wild-type strain. In the present study, the strain no. YM1504, able to grow in an iron-rich environment, was used as a potential organic iron supplement, and its efficacy in alleviating IDA in rats was investigated. Sixty female weanling Sprague-Dawley rats were randomly divided into a normal control group fed with a standard diet and a model group fed with an iron-deficient diet to create the IDA model. After the model was established, IDA rats were further randomly divided into five subgroups: the IDA group, the ferrous sulfate (FeSO4) group and Fe-YM1504 low-, medium- or high-dose groups receiving different concentrations of Fe-YM1504 supplements. Our results showed that Fe-YM1504 has an effective restorative function by returning the hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), serum iron (SI), total iron binding capacity (TIBC), serum ferritin (SF), etc. in IDA animals to the normal level. Moreover, malondialdehyde and the enzyme activities of superoxide dismutase and glutathione peroxidase in both plasma and liver homogenate were improved. Finally, compared with the FeSO4 group, the Fe-YM1504 middle-dose was more effective in alleviating IDA and fewer side effects were observed. The present study indicated that iron-enriched strain no. YM1504 might play a significant role in ameliorating IDA rats and might be exploited as a new iron supplement.

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