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Neural stem cells (NSCs) transplantation is a promising therapeutic strategy for ischemic stroke. However, significant cell death after transplantation greatly limits its effectiveness. Poly (trimethylene carbonate)15-F127-poly (trimethylene carbonate)15 (PTMC15-F127-PTMC15, PFP) is a biodegradable thermo-sensitive hydrogel biomaterial, which can control drug release and provide permissive substrates for donor NSCs. In our study, we seeded NSCs into PFP polymer scaffold loaded with three neurotrophic factors, including brain-derived neurotrophic factor, nerve growth factor, and Neurotrophin-3. And then we transplanted this NSCs-polymer scaffold in rat brains 14 days after middle cerebral artery occlusion. ELISA assay showed that PFP polymer scaffold sustained releasing three neurotrophic factors for at least 14 days. Western Blot and fluorescence immunostaining revealed that NSCs-polymer scaffold transplantation significantly reduced apoptosis of ischemic penumbra and promoted differentiation of the transplanted NSCs into mature neurons. Furthermore, infarct size was reduced, and neurological performance of the animals were improved by the transplanted NSCs-polymer scaffold. These results demonstrate that PFP polymer scaffold loaded with neurotrophic factors can enhance the effectiveness of stem cell transplantation therapy, which provides a new way for cell transplantation therapy in ischemic stroke.

Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.

Summary: Arbuscular mycorrhizal (AM) fungi play an important role in soil organic matter (SOM) formation and stabilization. Previous studies have emphasized organic compounds produced by AM fungi as persistent binding agents for aggregate formation and SOM storage. This concept overlooks the multiple biogeochemical processes mediated by AM fungal activities, which drive SOM generation, reprocessing, reorganization, and stabilization. Here, we propose an updated conceptual framework to facilitate a mechanistic understanding of the role of AM fungi in SOM dynamics. In this framework, four pathways for AM fungi‐mediated SOM dynamics are included: 'Generating', AM fungal exudates and biomass serve as key sources of SOM chemodiversity; 'Reprocessing', hyphosphere microorganisms drive SOM decomposition and resynthesis; 'Reorganizing', AM fungi mediate soil physical changes and influence SOM transport, redistribution, transformation, and storage; and 'Stabilizing', AM fungi drive mineral weathering and organo–mineral interactions for SOM stabilization. Moreover, we discuss the AM fungal role in SOM dynamics at different scales, especially when translating results from small scales to complex larger scales. We believe that working with this conceptual framework can allow a better understanding of AM fungal role in SOM dynamics, therefore facilitating the development of mycorrhiza‐based technologies toward soil health and global change mitigation. [ABSTRACT FROM AUTHOR]

The Microbiome Protocols eBook (MPB) is a valuable resource that provides standardized wet-lab protocols for microbiome research. The first edition, launched in 2020, received widespread acclaim and featured 152 meticulously curated protocols. The MPB aims to bridge the gaps in microbiome protocols and facilitate progress in the field by addressing challenges in wet experiments and data analysis. The upcoming second edition will incorporate updates from the first edition and expand into new areas, covering innovative methodologies and emerging technologies. The MPB is an open-access resource that is easily accessible to all researchers. [Extracted from the article]

Microglial HO‐1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co‐located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG‐mediated autophagy and HO‐1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf‐A1 or HO‐1 inhibitor ZnPP protected against hemin‐induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG‐mediated autophagy and HO‐1 signalling pathway. Knock‐down of FoxO3a inhibited autophagy and prevented hemin‐induced ferroptosis dependent of HO‐1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO‐1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro‐inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis‐induced striatum injury in the autologous blood‐induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG‐mediated autophagy and HO‐1 play an important role in microglial activation and ferroptosis‐induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH. [ABSTRACT FROM AUTHOR]