Introduction Macrophytes are essential for maintaining the health of shallow lake ecosystems, however, the driving and responsive relationship between ecological factors (such as seasonal changes and nutrition, etc.) and plant communities is not yet clear. Methods In this study, we conducted seasonal surveys of macrophyte community composition in lakes with different nutrient states, aiming to understand the incidence relation between macrophyte community diversity, seasonal changes and environmental factors. Results According to the classification criteria of comprehensive nutritional index, there were significant differences in the trophic status of the three lakes. Among them, the Xihu Lake has reached mild eutrophication with a TLI value of 56.33, both Cibi Lake and Haixihai Lake are mesotrophic with TLI value of 36.03 and 33.48, respectively. The results of diversity analysis showed a significant negative correlation between α-diversity (include Species richness, Shannon-Wiener index, Simpson index and Pielou index) and lake nutrient status. Among them, Xihu Lake showed the lowest α-diversity in all seasons, Haixihai Lake exhibited the middle α-diversity, Cibi Lake indicated the highest α-diversity. Non-metric multidimensional ordination showed that there were obvious spatial structures differences among the macrophyte communities in the three lakes. Macrophyte community composition in the three lakes was more similar in summer and autumn, but there was a wider gap in spring and winter. The redundancy analysis indicated distinct differences between diversity index and ecological factors, the eigenvalues of Axis 1 and Axis 2 being, respectively, 36.13% and 8.15%. Environmental factors could explain 44.8% of the total variation in macrophyte communities structure. Among these, nitrogen, phosphorus, water transparency and water temperature contributed 50.2%, 3.5%, 3.8% and 27.5%, respectively. Conclusions In summary, the community structure of macrophytes in plateau shallow lakes is co-regulated by seasons and nutrients.
Accumulating evidence showed that extracellular vesicles (EVs) and their cargoes are important information mediators in nervous system and have been proposed to play an important role in regulating regeneration. Moreover, many studies reported that olfactory ensheathing cells (OECs) conditioned medium is capable of promoting nerve regeneration and functional recovery. However, the role of EVs derived from OECs in axonal regeneration has not been clear. Thereby, the present study was designed to firstly isolate EVs from OECs culture supernatants, and then investigated their role in enhancing axonal regeneration after sciatic nerve injury. In vitro studies showed that OECs-EVs promoted axonal growth of dorsal root ganglion, which is dose-dependent and relies on their integrity. In vivo studies further demonstrated that nerve conduit containing OECs-EVs significantly enhanced axonal regeneration, myelination of regenerated axons and neurologically functional recovery in rats with sciatic nerve injury. In conclusion, our results, for the first time, demonstrated that OECs-EVs are capable of promoting nerve regeneration and functional recovery after peripheral nerve injuries in rats.
Delivery of multiple neurotrophic factors (NTFs), especially with time-restricted release kinetics, holds great potential for nerve repair. In this study, we utilized the tetracycline-regulatable Tet-On 3G system to control the expression of c-Jun, which is a common regulator of multiple NTFs in Schwann cells (SCs). In vitro, Tet-On/c-Jun-modified SCs showed a tightly controllable secretion of multiple NTFs, including glial cell line-derived NTF, nerve growth factor, brain-derived NTF, and artemin, by the addition or removal of doxycycline (Dox). When Tet-On/c-Jun-transduced SCs were grafted in vivo, the expression of NTFs could also be regulated by oral administration or removal of Dox. Fluoro-Gold retrograde tracing results indicated that a biphasic NTF expression scheme (Dox+3/−9, NTFs were up-regulated for 3 wk and declined to physiologic levels for another 9 wk) achieved more axonal regeneration than continuous up-regulation of NTFs (Dox+12) or no NTF induction (Dox−12). More importantly, the Dox+3/−9–group animals showed much better functional recovery than the animals in the Dox+12 and Dox−12 groups. Our findings, for the first time, demonstrated drug-controllable expression of multiple NTFs in nerve repair cells both in vitro and in vivo. These findings provide new hope for developing an optimal therapeutic alternative for nerve repair through the time-restricted release of multiple NTFs using Tet-On/c-Jun-modified SCs.—Huang, L., Xia, B., Shi, X., Gao, J., Yang, Y., Xu, F., Qi, F., Liang, C., Huang, J., Luo, Z. Time-restricted release of multiple neurotrophic factors promotes axonal regeneration and functional recovery after peripheral nerve injury. FASEB J. 33, 8600–8613 (2019). www.fasebj.org
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Previous studies have demonstrated abnormalities in functional connectivity (FC) of AD under the assumption that FC is stationary during scanning. However, studies on the FC dynamics of AD, which may provide more insightful perspectives in understanding the neural mechanisms of AD, remain largely unknown.Combining the sliding-window approach and the k-means algorithm, we identified three reoccurring dynamic FC states from resting-state fMRI data of 26 AD and 26 healthy controls. The between-group differences both in FC states and in regional temporal variability were calculated, followed by a correlation analysis of these differences with cognitive performances of AD patients.We identified three reoccurring FC states and found abnormal FC mainly in the frontal and temporal cortices. The temporal properties of FC states were changed in AD as characterized by decreased dwell time in State I and increased dwell time in State II. Besides, we found decreased regional temporal variability mainly in the somatomotor, temporal and parietal regions. Disrupted dynamic FC was significantly correlated with cognitive performances of AD patients.Our findings suggest abnormal dynamic FC in AD patients, which provides novel insights for understanding the pathophysiological mechanisms of AD.
Purpose: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system. Methods: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field. Results: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. Conclusion: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury. Keywords: Schwann cells, astrocytes, magnetic field, superparamagnetic iron oxide nanoparticles, spinal cord injury, cell orientation
Engelhardia roxburghiana Wall. is a traditional Chinese medicine used for treating cardiovascular diseases. Our previous study has implicated potential effects of total flavonoids of Engelhardia roxburghiana Wall. (TFER) against hyperlipidemia. The aim of the study is to uncover the effects and underlying mechanisms of TFER on foam cells formation after atherosclerosis. We used high fat diet (HFD) induced Apoe-/- mice and oxidized density lipoprotein (ox-LDL) induced THP-1 cells to mimic process of atherosclerosis in vivo and in vitro, respectively. Lipid accumulation, inflammation response, autophagosomes formation and expressions of autophagy related target genes were assessed. Our present study demonstrated TFER (500 mg/kg) alleviated macrophage infiltration and lipid accumulation in thoracic aortas of HFD-treated mice. In ox-LDL-treated THP-1 cells, MDC staining and Western blot analysis all indicated that the TFER (200 μg/ml) reduced foam cells formation and IL-1β releasing, activated autophagy through suppressing AKT/mTOR signaling, significantly regulating expressions of AKT, p-AKT, mTOR, p-mTOR, Beclin 1, LC3-II, p62. It is suggested that TFER alleviated atherosclerosis progression in vivo and in vitro through reducing foam cells formation and inflammatory responses, and the possible mechanism may be due to the activation of macrophage autophagy by inhibiting AKT and mTOR phosphorylation.