Mechanism of M2 macrophages modulating astrocyte polarization through the TGF-ß/PI3K/Akt pathway.

Recent studies have revealed that activated astrocytes (AS) are divided into two distinct types, termed A1 and A2. A2 astrocytes are neuroprotective and promote tissue repair and regeneration following spinal cord injury. Whereas, the specific mechanism for the formation of the A2 phenotype remains unclear. This study focused on the PI3K/Akt pathway and examined whether TGF-ß secreted by M2 macrophages could mediate A2 polarization by activating this pathway. In this study, we revealed that both M2 macrophages and their conditioned medium (M2-CM) could facilitate the secretion of IL-10, IL-13 and TGF-ß from AS, and this effect was significantly reversed after the administration of SB431542 (a TGF-ß receptor inhibitor) or LY294002 (a PI3K inhibitor). Moreover, immunofluorescence results demonstrated that TGF-ß secreted by M2 macrophages could facilitate the expression of A2 biomarker S100A10 in AS; combined with the results of western blot, it was found that this effect was closely related to the activation of PI3K/Akt pathway in AS. In conclusion, TGF-ß secreted by M2 macrophages may induce the conversion of AS to the A2 phenotype through the activation of the PI3K/Akt pathway.

Fresh human amniotic membrane effectively promotes the repair of injured common peroneal nerve.

Suture and autologous nerve transplantation are the primary therapeutic measures for completely severed nerves. However, imbalances in the microenvironment and adhesion of surrounding tissues can affect the quality of nerve regeneration and repair. Previous studies have shown that human amniotic membrane can promote the healing of a variety of tissues. In this study, the right common peroneal nerve underwent a 5-mm transection in rats. Epineural nerve repair was performed using 10/0 non-absorbable surgical suture. The repair site was wrapped with a two-layer amniotic membrane with α-cyanoacrylate rapid medical adhesive after suture. Hindlimb motor function was assessed using footprint analysis. Conduction velocity of the common peroneal nerve was calculated by neural electrical stimulation. The retrograde axoplasmic transport of the common peroneal nerve was observed using fast blue BB salt retrograde fluorescent staining. Hematoxylin-eosin staining was used to detect the pathological changes of the common peroneal nerve sputum. The mRNA expression of axon regeneration-related neurotrophic factors and inhibitors was measured using real-time polymerase chain reaction. The results showed that the amniotic membrane significantly improved the function of the injured nerve; the toe spread function rapidly recovered, the nerve conduction velocity was restored, and the number of fast blue BB salt particles were increased in the spinal cord. The amniotic membrane also increased the recovery rate of the tibialis anterior muscle and improved the tissue structure of the muscle. Meanwhile, mRNA expression of nerve growth factor, growth associated protein-43, collapsin response mediator protein-2, and brain-derived neurotrophic factor recovered to near-normal levels, while Lingo-1 mRNA expression decreased significantly in spinal cord tissues. mRNA expression of glial-derived neurotrophic factor did not change significantly. Changes in mRNA levels were more significant in amniotic-membrane-wrapping-treated rats compared with model and nerve sutured rats. These results demonstrate that fresh amniotic membrane wrapping can promote the functional recovery of sutured common peroneal nerve via regulation of expression levels of neurotrophic factors and inhibitors associated with axonal regeneration. The study was approved by the Committee on Animal Research and Ethics at the Affiliate Hospital of Zunyi Medical University, China (approval No. 112) on December 1, 2017.

Improvement of ginsenoside Rg1 on hematopoietic function in cyclophosphamide-induced myelosuppression mice.

This study was aimed to investigate the effects of ginsenoside Rg1 (Rg1) on hematopoietic function of bone marrow in cyclophosphamide-induced bone marrow depression mice. Mice were given cyclophosphamide (150mg/kg, i.p. for three days) to produce bone marrow depression. Rg1 was then administrated at 7.5 and 15mg/kg by i.p. for seven days. Bone marrow cells number was counted, and the percentage of hematopoietic stem cells (Lin(-)Sca-1(+)c-kit(+)) was quantified by flow cytometry. The histology of femoral bone was examined by H&E staining. The expression of calcium-sensing receptor mRNA was determined by the real time RT-PCR. Rg1 (7.5 and 15mg/kg) protected against cyclophosphamide-induced bone marrow depression, as evidenced by increased bone marrow cell numbers and improved femoral bone morphology. The percentage of Lin(-)Sca-1(+)c-kit(+) cells and lymphoid lineage CD3(+) cells were lower in cyclophosphamide group, but returned towards normal after Rg1 treatment in both bone marrow and peripheral blood cells. Expression of calcium-sensing receptor mRNA was increased in bone marrow cells on the 10th day after cyclophosphamide, but it was returned to normal level after Rg1 treatment. Rg1 alone did not produce these changes in normal mice. These results demonstrated that Rg1 improved hematopoietic function of bone marrow in cyclophosphamide-induced myelosuppression.