Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke / 医学前沿

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor cells in rats with cerebral ischemia / 医学前沿

Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.

PET/CT imaging manifestations of different pathological subtypes of liposarcoma / 浙江大学学报·医学版

OBJECTIVE@#To analyze PET/CT imaging manifestations of different pathological subtypes of liposarcoma.@*METHODS@#The F-fluorodeoxyglucose(FDG) PET/CT features of 13 patients pathologically confirmed as liposarcoma were retrospectively reviewed. The metabolism degree and distribution of different subtypes of liposarcoma were compared.@*RESULTS@#The well-differentiated liposarcoma showed fat density mass with septa and irregular strip with mild FDG uptake. The myxoid liposarcoma showed cystic or cystic solid mass, single or multiple with mild-moderate FDG uptake heterogeneously or homogeneously. The dedifferentiated liposarcoma showed mixed soft tissue mass with high FDG uptake heterogeneously, larger lesion with necrosis centrally. The mixed type contained well differentiated type and dedifferentiated type, and showed multiple lesion with combined imaging manifestations. There were local invasions in 12 cases, no lymph node matastasis, and the recurrence of dedifferentiated liposarcoma with lung metastasis in 1 case. The maximum standard values (SUVmax) of FNCCLE grade G1, G2 and G3 liposarcoma were 3.00, 5.67 and 10.33, respectively; there was significant difference between G1 and G3 groups, G2 and G3 groups (all <0.05).@*CONCLUSIONS@#PET/CT manifestations of liposarcoma of various pathological subtypes are different. Preoperative PET/CT examination can clarify the pathological types, scope of tumor invasion and metastasis of liposarcoma, which provides more information for clinical decision-making and is helpful for the preparation of surgical plan.