The pandemic of coronavirus disease 2019 (COVID‐19) is continually worsening. Clinical treatment for COVID‐19 remains primarily supportive with no specific medicines or regimens. Here, the development of multifunctional alveolar macrophage (AM)‐like nanoparticles (NPs) with photothermal inactivation capability for COVID‐19 treatment is reported. The NPs, made by wrapping polymeric cores with AM membranes, display the same surface receptors as AMs, including the coronavirus receptor and multiple cytokine receptors. By acting as AM decoys, the NPs block coronavirus from host cell entry and absorb various proinflammatory cytokines, thus achieving combined antiviral and anti‐inflammatory treatment. To enhance the antiviral efficiency, an efficient photothermal material based on aggregation‐induced emission luminogens is doped into the NPs for virus photothermal disruption under near‐infrared (NIR) irradiation. In a surrogate mouse model of COVID‐19 caused by murine coronavirus, treatment with multifunctional AM‐like NPs with NIR irradiation decreases virus burden and cytokine levels, reduces lung damage and inflammation, and confers a significant survival advantage to the infected mice. Crucially, this therapeutic strategy may be clinically applied for the treatment of COVID‐19 at early stage through atomization inhalation of the NPs followed by NIR irradiation of the respiratory tract, thus alleviating infection progression and reducing transmission risk.
Common antigenic properties for p85 and p75 but a different antigenic character for p71 Aleutian disease virus (ADV) proteins were demonstrated by Western blot analysis with monoclonal antibodies. It was shown that four hybridomas (ADV-Hy 47, 66, 77 and 84) with specific reactivity for structural proteins p85 and p75 also recognized p25 but not the p71, nonstructural, protein. In turn, the monoclonal antibody ADV-Hy 2 recognized the p71 protein only. For further studies of their antigenic properties, the ADV proteins were subjected to enzymatic or chemical cleavage. The derived peptide fragments were analyzed by epitopic mapping. Depending on the cleavage reagent and monoclonal antibody applied, specific peptide maps were revealed. The maps of p85 and p75 were very similar, indicating that both proteins shared an extensive antigenic relationship. After cleavage with α-chymotrypsin and N-chlorosuccinimide and by using the ADV-Hy 84 monoclonal antibody, unique peptide fragments were identified with p85 which had no counterparts in p75 fragments.
Introduction Vertical bone augmentation without osseous walls to support the stability of clots and bone grafts remains a challenge in dental implantology. The objectives of this study were to confirm that cortical perforation of the recipient bed is necessary and to evaluate whether nanohydroxyapatite (nHA) block grafts coated with recombinant human vascular endothelial growth factor 165 (rhVEGF 165 ) and cortical perforation can improve vertical bone regeneration. Materials and Methods We prepared nHA blocks coated with or without rhVEGF 165 on the rabbit calvarium through cortical perforation, and designated the animals as the nonperforated group (N-nHA), rhVEGF 165 group (NV-nHA), perforated group (P-nHA) and rhVEGF 165 on perforated group (PV-nHA). Micro-computed tomography (micro-CT) and fluorescence microscopy were selected to evaluate parameters of vertical bone regeneration at 4 and 6 weeks. Results The ratio of the newly formed bone volume to the titanium dome volume (BV/TV) and the bone mineral density (BMD) were significantly higher in the PV-nHA group than in the N-nHA group at 4 and 6 weeks, as determined using micro-CT. The fluorescence analysis showed slightly greater increases in new bone regeneration (NB%) and vertical height (VH%) gains in the P-nHA group than in the N-nHA group. Greater increases in NB% and VH% were observed in groups treated with rhVEGF 165 and perforation than in the blank groups, with significant differences detected at 4 and 6 weeks (N-nHA compared with PV-nHA, p<0.05). A greater VH% that was observed at the midline of the block in the PV-nHA group than in the other three groups at both time points (0.75±0.53% at 4 weeks and 0.83±0.42% at 6 weeks). Conclusion According to the present study, cortical perforation is necessary and nHA blocks coated with rhVEGF 165 and decoration could work synergistically to improve vertical bone regeneration by directly affecting primary osteoblasts and promoting angiogenesis and osteoinduction.
Psoriasis is a chronic inflammatory skin disease that is associated with multiple coexisting conditions. Extensive literature suggests that psoriasis is a T-cell-mediated condition, and its pathogenesis is related to dysfunction of the immune system. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that have suppressive effects on T cells. MDSCs are present at very low levels in healthy individuals but can substantially expand in tumours or inflammatory conditions. PSORI-CM02, a Chinese medical formula designed based on the Chinese medicine theory (Blood Stasis), has been prescribed extensively for psoriasis therapy and shows a stable clinical effect and safety. This study discusses the mechanisms of MDSCs involved in disease development and therapeutic progress. Our data provides evidence that monocytic myeloid-derived suppressor cells (M-MDSCs) play a role in IMQ-induced psoriatic dermatitis. Functional characterization and correlation analysis indicated that MDSCs are positively correlated with Th17 cells. PSORI-CM02 alleviated IMQ-induced psoriatic dermatitis and suppressed the proliferation of Th17 cells via M-MDSC-induced Arg1 upregulation, suggesting M-MDSCs could be a novel therapeutic target for psoriasis, and PSORI-CM02 exerted its effects via the perturbation of M-MDSCs and Th17 cell crosstalk.
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