Size-dependent gold nanoparticles induce macrophage M2 polarization and promote intracellular clearance of Staphylococcus aureus to alleviate tissue infection.

Tissue infection typically results from blood transmission or the direct inoculation of bacteria following trauma. The pathogen-induced destruction of tissue prevents antibiotics from penetrating the infected site, and severe inflammation further impairs the efficacy of conventional treatment. The current study describes the size-dependent induction of macrophage polarization using gold nanoparticles. Gold nanoparticles with a diameter of 50 â€‹nm (Au50) can induce M2 polarization in macrophages by inhibiting the NF-κB signaling pathway and stimulate an inflammatory response in the environment by inhibiting the MAPK signaling pathway LPS. Furthermore, the induced polarization and anti-inflammatory effects of the Au50 nanoparticles promoted the osteogenic differentiation of BMSCs in vitro. In addition, the overexpression of TREM2 in macrophage induced by Au50 nanoparticles was found to promote macrophage phagocytosis of Staphylococcus aureus, enhance the fusion of autophagosomes and lysosomes, accelerate the intracellular degradation of S. aureus, in addition to achieving an effective local treatment of osteomyelitis and infectious skin defects in conjunction with inflammatory regulation and accelerating bone regeneration. The findings, therefore, demonstrate that Au50 nanoparticles can be utilized as a promising nanomaterial for in vivo treatment of infections.

Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection

The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblasts susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antivirus drug tests and safety evaluation.

Role of exosomes in regeneration of peripheral nerve after injury and the progress in application / 中华显微外科杂志

Peripheral nerve injury is common in clinical practice. Today, outcomes of peripheral nerve repair are still not satisfactory. Recently, a large number of studies have shown that exosomes and their bioactive substances can repair peripheral nerve injury by mediating axonal regeneration, activating Schwann cells, regulating inflammation and other pathways to restore nerve function. This review aims to summarise and prospect the role and application of exosomes in peripheral nerve repair from the perspective of Schwann cells, mesenchymal stem cells and macrophages derived exosomes and their bioactive substances.