Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.

Neuroblastoma of the lumbosacral canal in an adult: a case report and literature review.

Neuroblastoma (NB) is a leading cause of death in children. It usually occurs in the adrenal gland and rarely in the spinal canal. Here, we report the case of a 48-year-old male patient with abnormal thickening of the cauda equina nerve as revealed by lumbosacral magnetic resonance imaging. The patient's main clinical manifestations were numbness and pain in both lower limbs. The patient underwent surgical treatment; however, intraoperatively, an unclear border was observed between the cauda equina nerve and the tumor; therefore, the tumor was not forcibly excised. The postoperative pathological results were reported as NB. The disease known as NB, which is extremely rare. We believe that a pathological biopsy is extremely vital for diagnosing NB, and aggressive post-operative radio-chemotherapy could potentially prolong the patient's survival time.

Electrical stimulation accelerates Wallerian degeneration and promotes nerve regeneration after sciatic nerve injury.

Following peripheral nerve injury (PNI), Wallerian degeneration (WD) in the distal stump can generate a microenvironment favorable for nerve regeneration. Brief low-frequency electrical stimulation (ES) is an effective treatment for PNI, but the mechanism underlying its effect on WD remains unclear. Therefore, we hypothesized that ES could enhance nerve regeneration by accelerating WD. To verify this hypothesis, we used a rat model of sciatic nerve transection and provided ES at the distal stump of the injured nerve. The injured nerve was then evaluated after 1, 4, 7, 14 and 21 days post injury (dpi). The results showed that ES significantly promoted the degeneration and clearance of axons and myelin, and the dedifferentiation of Schwann cells. It upregulated the expression of BDNF and NGF and increased the number of monocytes and macrophages. Through transcriptome sequencing, we systematically investigated the effect of ES on the molecular processes involved in WD at 4 dpi. Evaluation of nerves bridged using silicone tubing after transection showed that ES accelerated early axonal and vascular regeneration while delaying gastrocnemius atrophy. These results demonstrate that ES promotes nerve regeneration by accelerating WD and upregulating the expression of neurotrophic factors.

TRPC6 interacted with KCa1.1 channels to regulate the proliferation and apoptosis of glioma cells.

Malignant glioma is the most aggressive and deadliest brain malignancy. TRPC6 and KCa1.1, two ion channels, have been considered as potential therapeutic targets for malignant glioma treatment. TRPC6, a Ca2+-permeable channel, plays a vital role in promoting tumorigenesis and the progression of glioma. KCa1.1, a large-conductance Ca2+-activated channel, is also involved in growth and migration of glioma. However, the underlying mechanism by which these two ion channels promote glioma progression was unclear. In our study, we found that TRPC6 upregulated the expression of KCa1.1, while the immunoprecipitation analysis also showed that TRPC6 interacts with KCa1.1 channels in glioma cells. The currents of KCa1.1 recorded by the whole-cell patch clamp technique were increased by TRPC6 in glioma cells, suggesting that TRPC6 can provide a Ca2+ source for the activation of KCa1.1 channels. It was also suggested that TRPC6 regulates the proliferation and apoptosis of glioma cells through KCa1.1 channels in vitro. Therefore, C6-bearing glioma rats were established to validate the results in vitro. After the administration of paxilline (a specific inhibitor of KCa1.1 channels), TRPC6-dependent growth of glioma was inhibited in vivo. We also found that TRPC6 enhanced co-expression with KCa1.1 in glioma. These all suggested that TRPC6/KCa1.1 signal plays a role in promoting the growth of glioma. Our results provided new evidence for TRPC6 and KCa1.1 as potential targets for glioma treatment.

Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.

Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1.

Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.

Solitary plasmacytoma of the occipital bone: a case report.

Solitary plasmacytoma (SP) of the skull is an uncommon clinical entity that is characterized by a localized proliferation of neoplastic monoclonal plasma cells. This case report describes a 50-year-old male that presented with a headache and an exophytic soft mass on the occiput. The diagnosis of SP was based on the pathological results and imaging examinations. The patient underwent occipital craniotomy, skull reconstruction and lower trapezius myocutaneous flap (LTMF) transplantation under general anaesthesia. The tumour was capsulized and extended to the subcutaneous and the subdural space through the dura mater with skull defects. The neoplasm of the occipital bone involved large areas of scalp and subcutaneous tissue, which resulted in a large postoperative scalp defect that was repaired using LTMF transplantation. All of the tumour was removed and the transplanted flap grew well. Follow-up at 5 months identified an aggressive mass lesion on the right frontal lobe. The patient received six cycles of the PAD chemotherapy regimen (bortezomib, doxorubicin and dexamethasone) and the lesion was significantly reduced. This case demonstrates that LTMF is an alternative approach for the repair of scalp and subcutaneous soft tissue defects caused by the excision of a large malignant tumour of the occipital region. Chemotherapy is the choice of treatment for neoplastic recurrence.