PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy.

PURPOSE: Stem cell transplantation is promising for temporal lobe epilepsy (TLE) treatment. This study aimed to use PET imaging for the investigation of dynamic metabolic changes after transplantation of human neural stem cells (NSCs) and human GABA progenitor cells (GPCs) in a rat model of TLE. METHODS: 18F-FDG PET imaging, video-electroencephalography (EEG), whole-cell patch-clamp recordings and immunostaining were performed after transplantation of NSCs and GPCs. RESULTS: PET imaging demonstrated that glucose metabolism was gradually improved in the NSCs group, but decreased in GPCs and the control. Video-EEG manifested that seizures were suppressed after NSCs or GPCs transplantation; whole-cell patch-clamp confirmed increased inhibitory response of GPC-derived cells; immunostaining studies verified that the transplanted NSCs and GPCs could survive, migrate and differentiate into mature neuronal subtypes. CONCLUSION: 18F-FDG PET imaging could be a distinguishing approach for evaluation of dynamic glycolytic metabolic changes after transplantation of NSCs and GPCs in TLE. Whole-cell patch-clamp provides evidence for functional maturation and integration of transplanted stem cells within host circuits.

AKAP2 overexpression modulates growth plate chondrocyte functions through ERK1/2 signaling.

In our previous study, the mutation c.2645A > C (p. E882A) was found in the A-Kinase Anchoring Protein 2 (AKAP2) gene, which plays an important role in regulating the development of the skeletal system; however, the specific effect of AKAP2 on chondrocyte proliferation and differentiation and the potential mechanism are still not clear. In the present study, we investigated the effect of AKAP2 in vitro. We successfully isolated human growth plate chondrocytes (GPCs) from growth plate cartilage tissues and identified GPCs by aggrecan expression and flow cytometric analysis. AKAP2 overexpression significantly promoted GPC proliferation, enhanced GPC differentiation, and promoted extracellular matrix (ECM) synthesis, whereas AKAP2 silencing exerted the opposite effects on GPCs. AKAP2 overexpression increased, while AKAP2 silencing decreased, the protein levels of p-extracellular regulated protein kinases (ERK)1/2. More importantly, the promotive effects of AKAP2 overexpression on GPC proliferation, differentiation, and ECM synthesis were significantly reversed by the ERK1/2 signaling antagonist U0126, suggesting that AKAP2 enhances GPC functions through ERK1/2 signaling. In conclusion, we demonstrate AKAP2 overexpression-induced enhancement of GPC functions through ERK1/2 signaling. Considering the critical role of GPC functions in adolescent idiopathic scoliosis (AIS) pathogenesis, the application of AKAP2 targeting in AIS treatment should be investigated in future studies.

Metabolomics reveals sex-specific metabolic shifts and predicts the duration from positive to negative in non-severe COVID-19 patients during recovery process.

Metabolic profiling in COVID-19 patients has been associated with disease severity, but there is no report on sex-specific metabolic changes in discharged survivors. Herein we used an integrated approach of LC-MS-and GC-MS-based untargeted metabolomics to analyze plasma metabolic characteristics in men and women with non-severe COVID-19 at both acute period and 30 days after discharge. The results demonstrate that metabolic alterations in plasma of COVID-19 patients during the recovery and rehabilitation process were presented in a sex specific manner. Overall, the levels of most metabolites were increased in COVID-19 patients after the cure relative to acute period. The major plasma metabolic changes were identified including fatty acids in men and glycerophosphocholines and carbohydrates in women. In addition, we found that women had shorter length of hospitalization than men and metabolic characteristics may contribute to predict the duration from positive to negative in non-severe COVID-19 patients. Collectively, this study shed light on sex-specific metabolic shifts in non-severe COVID-19 patients during the recovery process, suggesting a sex bias in prognostic and therapeutic evaluations based on metabolic profiling.

Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage.

During brain development, neural stem cells (NSCs) initially produce neurons and change their fate to generate glias. While the regulation of neurogenesis is well characterized, specific markers for glial precursor cells (GPCs) and the master regulators for gliogenesis remain unidentified. Accumulating evidence suggests that RNA-binding proteins (RBPs) have significant roles in neuronal development and function, as they comprehensively regulate the expression of target genes in a cell-type-specific manner. We systematically investigated the expression profiles of 1,436 murine RBPs in the developing mouse brain and identified quaking (Qk) as a marker of the putative GPC population. Functional analysis of the NSC-specific Qk-null mutant mouse revealed the key role of Qk in astrocyte and oligodendrocyte generation and differentiation from NSCs. Mechanistically, Qk upregulates gliogenic genes via quaking response elements in their 3' untranslated regions. These results provide crucial directions for identifying GPCs and deciphering the regulatory mechanisms of gliogenesis from NSCs.

Effects of dietary grape proanthocyanidins on the growth performance, jejunum morphology and plasma biochemical indices of broiler chicks.

Grape proanthocyanidins (GPCs) are a family of naturally derived polyphenols that have aroused interest in the poultry industry due to their versatile role in animal health. This study was conducted to investigate the potential benefits and appropriate dosages of GPCs on growth performance, jejunum morphology, plasma antioxidant capacity and the biochemical indices of broiler chicks. A total of 280 newly hatched male Cobb 500 broiler chicks were randomly allocated into four treatments of seven replicates each, and were fed a wheat-soybean meal-type diet with or without (control group), 7.5, 15 or 30 mg/kg of GPCs. Results show that dietary GPCs decrease the feed conversion ratio and average daily gain from day 21 to day 42, increase breast muscle yield by day 42 and improve jejunum morphology between day 21 and day 42. Chicks fed 7.5 and 15 mg/kg of GPCs show increased breast muscle yield and exhibit improved jejunum morphologies than birds in the control group. Dietary GPCs fed at a level of 15 mg/kg markedly increased total superoxide dismutase (T-SOD) activity between day 21 and day 42, whereas a supplement of GPCs at 7.5 mg/kg significantly increased T-SOD activity and decreased lipid peroxidation malondialdehyde content by day 42. A supplement of 30 mg/kg of GPCs has no effect on antioxidant status but adversely affects the blood biochemical indices, as evidenced by increased creatinine content, increased alkaline phosphatase by day 21 and increased alanine aminotransferase by day 42 in plasma. GPC levels caused quadratic effect on growth, jejunum morphology and plasma antioxidant capacity. The predicted optimal GPC levels for best plasma antioxidant capacity at 42 days was 13 to 15 mg/kg, for best feed efficiency during grower phase was 16 mg/kg, for best jejunum morphology at 42 days was 17 mg/kg. In conclusion, GPCs (fed at a level of 13 to 17 mg/kg) have the potential to be a promising feed additive for broiler chicks.

A Novel Approach for Amplification and Purification of Mouse Oligodendrocyte Progenitor Cells.

Although transgenic and knockout mice are widely used to study the specification and differentiation of oligodendrocyte precursor cells (OPCs), mouse primary OPCs are difficult to be purified and maintained, and many in vitro studies have to resort to rat OPCs as substitutes. In this study, we reported that mouse O4 negative early-stage OPCs can be obtained by culturing cortical tissue blocks, and the simultaneous treatment of OPCs with Platelet Derived Growth Factor-AA (PDGFaa), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) is the key for the propagation of mouse OPCs in culture. EGF was found to be a potent mitogen for OPCs and cooperate with PDGFaa to extend cell division and inhibit their differentiation. EGF also collaborates with PDGFaa and bFGF to convert bipolar or tripolar OPCs to more vital fibroblast-like OPCs without compromising their oligodendrocyte differentiation potential. In addition, EGF promoted the survival and proliferation of glial progenitor cells (GPCs) derived from primary OPC cultures, and a mixture of GPCs and OPCs can be obtained and propagated in the presence of EGF, bFGF, and PDGFaa. Once EGF is withdrawn, GPC population decreased sharply and fibroblast-like OPCs changed into typical OPCs morphology, then homogeneous OPCs were obtained subsequently.