Nerve injury is a common condition that occurs as a result of trauma, iatrogenic injury, or long-lasting stimulation. Unlike the central nervous system (CNS), the peripheral nervous system (PNS) has a strong capacity for self-repair and regeneration. Peripheral nerve injury results in the degeneration of distal axons and myelin sheaths. Macrophages and Schwann cells (SCs) can phagocytose damaged cells. Wallerian degeneration (WD) makes the whole axon structure degenerate, creating a favorable regenerative environment for new axons. After nerve injury, macrophages, neutrophils and other cells are mobilized and recruited to the injury site to phagocytose necrotic cells and myelin debris. Pro-inflammatory and anti-inflammatory factors involved in the inflammatory response provide a favorable microenvironment for peripheral nerve regeneration and regulate the effects of inflammation on the body through relevant signaling pathways. Previously, inflammation was thought to be detrimental to the body, but further research has shown that appropriate inflammation promotes nerve regeneration, axon regeneration, and myelin formation. On the contrary, excessive inflammation can cause nerve tissue damage and pathological changes, and even lead to neurological diseases. Therefore, after nerve injury, various cells in the body interact with cytokines and chemokines to promote peripheral nerve repair and regeneration by inhibiting the negative effects of inflammation and harnessing the positive effects of inflammation in specific ways and at specific times. Understanding the interaction between neuroinflammation and nerve regeneration provides several therapeutic ideas to improve the inflammatory microenvironment and promote nerve regeneration.

Peripheral nerve injuries, caused by various reasons, often lead to severe sensory, motor, and autonomic dysfunction or permanent disability, posing a challenging problem in regenerative medicine. Autologous nerve transplantation has been the gold standard in traditional treatments but faces numerous limitations and risk factors, such as donor area denervation, increased surgical complications, and diameter or nerve bundle mismatches. The extracellular matrix (ECM) is a complex molecular network synthesized and released into the extracellular space by cells residing in tissues or organs. Its main components include collagen, proteoglycans/glycosaminoglycans, elastin, laminin, fibronectin, etc., providing structural and biochemical support to surrounding cells, crucial for cell survival and growth. Schwann cells, as the primary glial cells in the peripheral nervous system, play various important roles. Schwann cell transplantation is considered the gold standard in cell therapy for peripheral nerve injuries, making ECM derived from Schwann cells one of the most suitable biomaterials for peripheral nerve repair. To better understand the mechanisms of Schwann cells and the ECM in peripheral nerve regeneration and their optimal application, this review provides an overview of their roles in peripheral nerve regeneration.

Background: It is urgent to explore an effective potential therapeutic strategy for ESCC. In recent years, cell-based cancer immunotherapy has become a potentially close for carcinoma therapy. Chimeric antigen receptor (CAR) T cell technology is a kind of adoptive cell therapy technique which has been developed rapidly. We sought to obtain EphA2.CAR-T cell and revealed the ability of EphA2.CAR-T cells to kill esophageal squamous cell carcinoma (ESCC) cells in vitro. Methods: Firstly, the expression and location of EphA2 in ESCC tissues and cells was tested by immunohistochemistry staining and Western blot. Secondly, the second generation of EphA2.CAR was constructed via molecular biology technology, and transduced into T cells to obtain the EphA2.CAR-T cell. The transduction efficacies were assessed using flow cytometry (FCM). Thirdly, the effect of cell killing of EphA2.CAR-T cell on ESCC cells in vitro was detected by co-culture experiments. The productions of cytokines (TNF-α and IFN-γ) by EphA2.CAR-T cell after co-culture with ESCC cells were analyzed by ELISA assay. Results: The expression of EphA2 was significantly upregulated in ESCC tissues and cells (P<0.05). EphA2 was expressed on the membrane of ESCC cells, so it could be served as tumor-associated surface antigens (TAA) of CAR for ESCC treatment. The EphA2.CAR-T cell was obtained successfully, and its’ transduction efficacies was 61.4% by FCM. The ability of cell killing of EphA2.CAR-T cell was better than that of T cells (P<0.01), and demonstrated a dose-dependent cell killing. The results of ELISA assay showed that the levels of TNF-α and IFN-γ in EphA2.CAR-T cells were notably raised compared with T cells (P<0.05). Conclusions: We firstly constructed the second generation of EphA2.CAR and established EphA2.CAR-T cells. The EphA2.CAR-T cells showed a dose-dependent cell killing of ESCC cells, and promoted the production of cytokines in vitro. These findings open a new way for treatment of ESCC by immunotherapy in the future.

Background: Peripheral nerves have a certain regenerative ability, but their repair and regeneration after injury is a complex process, usually involving a large number of genes and proteins. In a previous study, we analyzed the gene expression profile in rats after sciatic nerve injury and found significant changes in transforming growth factor-beta 1 (TGF-β1) expression, suggesting that TGF-β1 may be involved in the process of nerve regeneration after injury. Methods: In this study, we first detected the time-course expression and localization of TGF-β1 in dorsal root ganglion (DRG) tissues in a rat sciatic nerve transection model via RT-qPCR. Secondly, we investigated the bioactive roles of TGF-β1 in primary cultured DRG neuron cells through a CCK8 assay, TUNEL assay, and immunofluorescence staining. Thirdly, we explored the neuroprotective roles of TGF-β1 in an in vivo model of sciatic nerve regeneration through morphological observation, behavioral, and electrophysiological tests, and a molecular biological measure. Results: We found that TGF-β1 expression was increased after injury and mainly located in the cytoplasm and nuclei of neuron cells in the DRG. TGF-β1 may regulate the viability, apoptosis, and neurite outgrowth of primary DRG neuron cells. In our in vivo model of sciatic nerve regeneration, TGF-β1 improved nerve regeneration and neuronal function recovery after sciatic nerve injury, alleviated the inflammatory response, and relieved neuropathic pain via the TGF-β1/smad2 pathway. Conclusions: This study provides an experimental and theoretical basis for using TGF-β1 as a neuroprotective agent after peripheral nerve injury in clinical practice in the future.

Background: Long non-coding RNAs (lncRNAs) have important effects on the development and progression of multiple carcinomas. Our studies aimed to investigate the expression of lncRNA DANCR in esophageal squamous cell carcinoma (ESCC) tissues and paracancerous tissues, and to explore its effect on the cell biological characteristics of ESCC ECA109 cells. Methods: The expression of DANCR was detected by qRT-PCR in human ESCC tissues and paracancerous normal tissues in ESCC patients. Small interfering RNA (siRNA) was transfected to knock down the expression of DANCR and interference efficiency was analyzed by qRT-PCR in ECA109 cells. MTT, wound healing, Transwell, TUNEL and flow cytometry (FCM) assay was used to measure the influence of DANCR on proliferation, invasion, migration and apoptosis in ECA109 cells, respectively. Results: The expression of DANCR in ESCC tissues and ESCC cells was significantly higher compared with that in the adjacent normal tissues (P<0.05). Furthermore, cell proliferation, migration and invasion were significantly suppressed by knock-down mediated down-regulation of DANCR expression. On the contrary, cell apoptosis was promoted by silencing of DANCR. Conclusions: According to our research, the expression of DANCR was up-regulated in human ESCC tissues, and the important role that DANCR played in ESCC cells was similar to an oncogene. Therefore, silencing of lncRNA DANCR could have potentially beneficial effects on the prognostic and therapy for ESCC in the future.