Transcriptional Signatures of a Dynamic Epilepsy Process Reveal Potential Immune Regulation.

Epilepsy is a progression of development and advancement over time. However, the molecular features of epilepsy were poorly studied from a dynamic developmental perspective. We intend to investigate the key mechanisms in the process of epilepsy by exploring the roles of stage-specifically expressed genes. By using time-course transcriptomic data of epileptic samples, we first analyzed the molecular features of epilepsy in different stages and divided it into progression and remission stages based on their transcriptomic features. 34 stage-specifically expressed genes were then identified by the Tau index and verified in other epileptic datasets. These genes were then enriched for immune-related biological functions. Furthermore, we found that the level of immune infiltration and mechanisms at different stages were different, which may result from different types of immune cells playing leading roles in distinct stages. Our findings indicated an essential role of immune regulation as the potential mechanism of epilepsy development.

Spatiotemporal expression patterns of genes coding for plasmalemmal chloride transporters and channels in neurological diseases.

Neuronal voltage changes which are dependent on chloride transporters and channels are involved in forming neural functions during early development and maintaining their stability until adulthood. The intracellular chloride concentration maintains a steady state, which is delicately regulated by various genes coding for chloride transporters and channels (GClTC) on the plasmalemma; however, the synergistic effect of these genes in central nervous system disorders remains unclear. In this study, we first defined 10 gene clusters with similar temporal expression patterns, and identified 41 GClTC related to brain developmental process. Then, we found 4 clusters containing 22 GClTC were enriched for the neuronal functions. The GClTC from different clusters presented distinct cell type preferences and anatomical heterogeneity. We also observed strong correlations between clustered genes and diseases, most of which were nervous system disorders. Finally, we found that one of the most well-known GClTC, SLC12A2, had a more profound effect on glial cell-related diseases than on neuron-related diseases, which was in accordance with our observation that SLC12A2 was mainly expressed in oligodendrocytes during brain development. Our findings provide a more comprehensive understanding of the temporal and spatial expression characteristics of GClTC, which can help us understand the complex roles of GClTC in the development of the healthy human brain and the etiology of brain disorders.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Updated Evaluation of Robotic- and Video-Assisted Thoracoscopic Lobectomy or Segmentectomy for Lung Cancer: A Systematic Review and Meta-Analysis.

Objectives: Robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) are the two principal minimally invasive surgical approaches for patients with lung cancer. This study aimed at comparing the long-term and short-term outcomes of RATS and VATS for lung cancer. Methods: A comprehensive search for studies that compared RATS versus VATS for lung cancer published until November 31, 2021, was conducted. Data on perioperative outcomes and oncologic outcomes were subjected to meta-analysis. PubMed, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before November 2021. Results: Twenty-six studies comparing 45,733 patients (14,271 and 31,462 patients who underwent RATS and VATS, respectively) were included. The present meta-analysis showed that there were no significant differences in operative time, any complications, tumor size, chest drain duration, R0 resection rate, lymph station, 5-year overall survival, and recurrence rate. However, compared with the VATS group, the RATS group had less blood loss, a lower conversion rate to open, a shorter length of hospital stay, more lymph node dissection, and better 5-year disease-free survival. Conclusions: RATS is a safe and feasible alternative to VATS for patients with lung cancer.

Adipose-derived stem cell transplantation improves learning and memory via releasing neurotrophins in rat model of temporal lobe epilepsy.

Epilepsy is a common neurological disease and its most common type is temporal lobe epilepsy (TLE). Novel therapeutics is needed as many TLE patients are resistant to treatments like anticonvulsants or temporal lobectomy. Stem cell therapy has great promise in regeneration medicine. In the current study, we tried to investigate the potential protective effects of adipose-derived stem cell (ADSC) transplantation in epileptic rats. Epilepsy model was established by intra-hippocampal injection of kainic acid (KA) in rats. ADSCs were isolated, differentiated and transplanted into hippocampus of KA rats. There were three groups of rats: normal control group receiving saline injection and no transplantation, KA + sham group receiving KA injection and sham transplantation surgery and KA + transplantation group receiving KA injection and ADSC transplantation. We found that ADSCs were highly positive for CD44, CD90, CD29 and CD105, and neural differentiation induced the expression of neuronal markers like Tuj1, MAP2, NeuN and PSD-95. EEG recording showed that KA induced seizure activity while ADSC transplantation inhibited seizure activity. In training session of Morris water maze task, KA injection impaired the learning capacity of rats while ADSC transplantation restored the learning capacity at 2-week or 2-month post transplantation. In probe session of Morris water maze task, KA injection impaired the memory of rats while ADSC transplantation restored the memory at 2-week or 2-month post transplantation. Transplanted ADSCs released BDNF, NT3 and NT4. Pro-apoptotic BAX was reduced while anti-apoptotic BCL-2 and BCL-xL were increased in hippocampus post ADSC transplantation. Our study suggests that ADSC transplantation inhibits KA-induced seizures and improves the learning and memory function of epileptic rats.

Early detection of Alzheimer's disease by peptides from phage display screening.

Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective treatment so far. As clinical trials show that early-stage patients are more likely to respond to potential interventions, various technologies have been used to search blood biomarkers for the early diagnosis of AD. Phage display could be used to select specific peptides against desired target and here, we established a peptide binding assay based on phage display peptide library to detect early-stage AD patients. We first selected peptides from phage display library against plasmas from AD patients (n = 10) and normal healthy controls (n = 10), respectively, in the discovery set. Then, we further characterized one AD-specific peptide (AD#1 peptide) and one control-specific peptide (Con#1 peptide), and evaluated their diagnostic performance in independent validation set (35 AD patients, 45 MCI, 45 controls and 20 PD patients). Our results show that both AD#1 peptide and Con#1 peptide could distinguish AD/MCI patients from controls and combination of these two peptides could greatly improve the diagnostic performance (AUC is above 0.80 in ROC curve analysis). In addition, we found that AD#1 peptide stained Aß-treated primary astrocyte and bound to recombinant human YKL-40 protein in in-vitro assay. It supports that AD#1 peptide detects AD inflammation related cytokine. Thus, the detection assay based on phage-derived peptides may offer a novel blood biomarker test for the early diagnosis of AD.