Schwann cells transplantation improves nerve injury and alleviates neuropathic pain in rats.

The mechanism of neuropathic pain induced by nerve injury is complex and there are no effective treatment methods. P2X4 receptor expression is closely related to the occurrence of pain. Schwann cells (SCs) play a key protective role in the repair of peripheral nerve injury and myelin sheath regeneration. However, whether SCs can affect the expression of P2X4 receptor and play a role in pathological pain is still unclear. Therefore, this study investigated the effect of SCs on whether they can down regulate the expression of P2X4 receptor to affect pain. The results showed that in the neuropathic pain induced by sciatic nerve injury model, the expression of P2X4 receptor in spinal cord tissue was significantly increased and the pain sensation of rats was increased. While SCs transplantation could down regulate the expression of P2X4 receptors in spinal cord and increase the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats. These data indicate that SCs can reduce the expression of P2X4 receptors to alleviate neuropathic pain, indicating that SCs can mediate P2X4 receptor signalling as a new target for pain treatment.

AKT/GSK-3beta/VEGF signaling is involved in P2RY2 activation-induced the proliferation and metastasis of gastric cancer.

Studies have revealed the contribution of ATP-G-protein-coupled P2Y2 receptor (P2RY2) in tumor progression, but the role of P2RY2 in regulating the progression of gastric cancer (GC) and related molecular mechanisms are relatively lacking. Therefore, this study investigates the effects of P2RY2 on the proliferation and migration of GC through in vivo and in vitro experiments. The results showed that P2RY2 was expressed in GC tissues and GC cell lines. Adenosine triphosphate (ATP) increased the calcium influx in AGS and HGC-27 cells, and was dose-dependent with ATP concentration. ATP and UTP increased the intracellular glycogen content, enhanced the actin fiber stress response, and promoted the proliferation and migration of GC cells, while P2RY2 competitive antagonist AR-C118925XX reversed the changes induced by ATP. Knockdown of P2RY2 expression by shRNA inhibited the proliferation of GC cells. Activation of P2RY2 increased the expression of Snail, Vimentin, and ß-catenin in GC cells, and down-regulated the expression of E-cadherin, while AR-C118925XX decreased the expression of these genes induced by ATP. Activation of P2RY2 activated AKT/GSK-3beta/VEGF signal to promote the proliferation of GC cells, and the P13/AKT signaling pathway LY294002 reversed the corresponding phenomenon, but no synergistic pharmacological properties of AR-C118925XX and LY294002 have been found. In vivo experiments showed that ATP-induced tumor growth, while AR-C118925XX inhibited ATP-induced tumor growth. Our conclusion is that P2RY2 activated the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of GC, suggesting that P2RY2 may be a new potential target for the treatment of GC.

Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease.

BACKGROUND: Anaemia of chronic disease (ACD) is the second most common type of anaemia and lacks an effective treatment. Patients with anaemia are reported to have altered gut microbial profiles, which may affect erythropoiesis. Here, we investigated the gut microbial features of patients with ACD and determined whether regulating gut microbiota using washed microbiota transplantation (WMT) was effective in treating ACD. METHODS: We compared the gut microbiota profile of patients with ACD and healthy controls, evaluated the efficacy of WMT on haematological parameters in the patients, and analysed the alterations in gut microbiota after WMT treatment. RESULTS: Patients with ACD had lower gut microbial richness, and differences in microbial composition and function, relative to healthy controls. Additionally, the relative abundances of two butyrate-producing genera Lachnospiraceae NK4A136 group and Butyricicoccus, were positively correlated with the haemoglobin (HGB) level and lower in patients with ACD than controls. WMT significantly increased HGB levels in patients with ACD. After the first, second and third WMT rounds, normal HGB levels were restored in 27.02%, 27.78% and 36.37% (all p < .05) of patients with ACD, respectively. Moreover, WMT significantly increased the abundance of butyrate-producing genera and downregulated gut microbial functions that were upregulated in patients with ACD. CONCLUSIONS: Patients with ACD exhibited differences in gut microbial composition and function relative to healthy controls. WMT is an effective treatment for ACD that reshapes gut microbial composition, restores butyrate-producing bacteria and regulates the functions of gut microbiota.

Application of cell transplantation in the treatment of neuropathic pain.

Nerve injury can not only lead to sensory and motor dysfunction, but also be complicated with neuropathic pain (NPP), which brings great psychosomatic injury to patients. At present, there is no effective treatment for NPP. Based on the functional characteristics of cell transplantation in nerve regeneration and injury repair, cell therapy has been used in the exploratory treatment of NPP and has become a promising treatment of NPP. In this article, we discuss the current mainstream cell types for the treatment of NPP, including Schwann cells, olfactory ensheathing cells, neural stem cells and mesenchymal stem cells in the treatment of NPP. These bioactive cells transplanted into the host have pharmacological properties of decreasing pain threshold and relieving NPP by exerting nutritional support, neuroprotection, immune regulation, promoting axonal regeneration, and remyelination. Cell transplantation can also change the microenvironment around the nerve injury, which is conducive to the survival of neurons. It can effectively relieve pain by repairing the injured nerve and rebuilding the nerve function. At present, some preclinical and clinical studies have shown that some encouraging results have been achieved in NPP treatment based on cell transplantation. Therefore, we discussed the feasible strategy of cell transplantation as a treatment of NPP and the problems and challenges that need to be solved in the current application of cell transplantation in NPP therapy.

Application of olfactory ensheathing cells in peripheral nerve injury and its complication with pathological pain.

Direct or indirect injury of peripheral nerve can lead to sensory and motor dysfunction, which can lead to pathological pain and seriously affect the quality of life and psychosomatic health of patients. While the internal repair function of the body after peripheral nerve injury is limited. Nerve regeneration is the key factor hindering the recovery of nerve function. At present, there is no effective treatment. Therefore, more and more attention have been paid to the development of foreground treatment to achieve functional recovery after peripheral nerve injury, including relief of pathological pain. Cell transplantation strategy is a therapeutic method with development potential in recent years, which can exert endogenous alternative repair by transplanting exogenous functional bioactive cells to the site of nerve injury. Olfactory ensheathing cells (OECs) are a special kind of glial cells, which have the characteristics of continuous renewal and survival. The mechanisms of promoting nerve regeneration and functional repair and relieving pathological pain by transplantation of OECs to peripheral nerve injury include secretion of a variety of neurotrophic factors, axonal regeneration and myelination, immune regulation, anti-inflammation, neuroprotection, promotion of vascular growth and improvement of inflammatory microenvironment around nerve injury. Different studies have shown that OECs combined with biomaterials have made some progress in the treatment of peripheral nerve injury and pathological pain. These biomaterials enhance the therapeutic effect of OECs. Therefore, the functional role of OECs in peripheral nerve injury and pathological pain was discussed in this paper.Although OECs are in the primary stage of exploration in the repair of peripheral nerve injury and the application of pain, but OECs transplantation may become a prospective therapeutic strategy for the treatment of peripheral nerve injury and pathological pain.

Therapeutic effect of exosomes derived from Schwann cells in the repair of peripheral nerve injury.

Peripheral nerve injury (PNI) can cause nerve demyelination, neuronal apoptosis, axonal atrophy, inflammatory infiltration, glial scar formation, and other pathologies that can lead to sensory and motor dysfunction and seriously affect the psychosomatic health of patients. There is currently no effective treatment method, so exploring a promising treatment method is of great significance. Several studies have revealed the therapeutic roles of Schwann cells (SCs) and their exosomes in nerve injury repair. Exosomes are extracellular nanovesicles secreted by cells that act as key molecules in intercellular communication. Progress has been made in understanding the role of exosomes derived from SCs (SC-EXOs) in peripheral nerve regeneration, including the promotion of axonal regeneration and myelin formation, anti-inflammation, vascular regeneration, neuroprotection, and neuroregulation. Therefore, in this paper, we summarize the functional characteristics of SC-EXOs and discuss their potential therapeutic effects on PNI repair as well as some existing problems and future challenges.

Therapeutic role of neural stem cells in neurological diseases.

The failure of endogenous repair is the main feature of neurological diseases that cannot recover the damaged tissue and the resulting dysfunction. Currently, the range of treatment options for neurological diseases is limited, and the approved drugs are used to treat neurological diseases, but the therapeutic effect is still not ideal. In recent years, different studies have revealed that neural stem cells (NSCs) have made exciting achievements in the treatment of neurological diseases. NSCs have the potential of self-renewal and differentiation, which shows great foreground as the replacement therapy of endogenous cells in neurological diseases, which broadens a new way of cell therapy. The biological functions of NSCs in the repair of nerve injury include neuroprotection, promoting axonal regeneration and remyelination, secretion of neurotrophic factors, immune regulation, and improve the inflammatory microenvironment of nerve injury. All these reveal that NSCs play an important role in improving the progression of neurological diseases. Therefore, it is of great significance to better understand the functional role of NSCs in the treatment of neurological diseases. In view of this, we comprehensively discussed the application and value of NSCs in neurological diseases as well as the existing problems and challenges.

G protein-coupled P2Y12 receptor is involved in the progression of neuropathic pain.

The pathological mechanism of neuropathic pain is complex, which seriously affects the physical and mental health of patients, and its treatment is also difficult. The role of G protein-coupled P2Y12 receptor in pain has been widely recognized and affirmed. After nerve injury, stimulated cells can release large amounts of nucleotides into the extracellular matrix, act on P2Y12 receptor. Activated P2Y12 receptor activates intracellular signal transduction and is involved in the development of pain. P2Y12 receptor activation can sensitize primary sensory neurons and receive sensory information. By transmitting the integrated information through the dorsal root of the spinal cord to the secondary neurons of the posterior horn of the spinal cord. The integrated information is then transmitted to the higher center through the ascending conduction tract to produce pain. Moreover, activation of P2Y12 receptor can mediate immune cells to release pro-inflammatory factors, increase damage to nerve cells, and aggravate pain. While inhibits the activation of P2Y12 receptor can effectively relieve pain. Therefore, in this article, we described P2Y12 receptor antagonists and their pharmacological properties. In addition, we explored the potential link between P2Y12 receptor and the nervous system, discussed the intrinsic link of P2Y12 receptor and neuropathic pain and as a potential pharmacological target for pain suppression.

P2Y12 receptor involved in the development of chronic nociceptive pain as a sensory information mediator.

Direct or indirect damage to the nervous system (such as inflammation or tumor invasion) can lead to dysfunction and pain. The generation of pain is mainly reflected in the activation of glial cells and the abnormal discharge of sensory neurons, which transmit stronger sensory information to the center. P2Y12 receptor plays important roles in physiological and pathophysiological processes including inflammation and pain. P2Y12 receptor involved in the occurrence of pain as a sensory information mediator, which enhances the activation of microglia and the synaptic plasticity of primary sensory neurons, and reaches the higher center through the ascending conduction pathway (mainly spinothalamic tract) to produce pain. While the application of P2Y12 receptor antagonists (PBS-0739, AR-C69931MX and MRS2359) have better antagonistic activity and produce analgesic pharmacological properties. Therefore, in this article, we discussed the role of the P2Y12 receptor in different chronic pains and its use as a pharmacological target for pain relief.

Potential role of Schwann cells in neuropathic pain.

Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the nociceptive stimulation is eliminated, and treatment is extremely challenging in such cases. Schwann cells (SCs) form the myelin sheaths around neuronal axons and play a crucial role in neural information transmission. SCs can secrete trophic factors to nourish and protect axons, and can further secrete pain-related factors to induce pain. SCs may be activated by peripheral nerve injury, triggering the transformation of myelinated and non-myelinated SCs into cell phenotypes that specifically promote repair. These differentiated SCs provide necessary signals and spatial clues for survival, axonal regeneration, and nerve regeneration of damaged neurons. They can further change the microenvironment around the regions of nerve injury, and relieve the pain by repairing the injured nerve. Herein, we provide a comprehensive overview of the biological characteristics of SCs, discuss the relationship between SCs and nerve injury, and explore the potential mechanism of SCs and the occurrence of NPP. Moreover, we summarize the feasible strategies of SCs in the treatment of NPP, and attempt to elucidate the deficiencies and defects of SCs in the treatment of NPP.

ATP ion channel P2X purinergic receptors in inflammation response.

Different studies have confirmed that P2X purinergic receptors play a key role in inflammation. Activation of P2X purinergic receptors can release inflammatory cytokines and participate in the progression of inflammatory diseases. In an inflammatory microenvironment, cells can release a large amount of ATP to activate P2X receptors, open non-selective cation channels, activate multiple intracellular signaling, release multiple inflammatory cytokines, amplify inflammatory response. While P2X4 and P2X7 receptors play an important role in the process of inflammation. P2X4 receptor can mediate the activation of microglia involved in neuroinflammation, and P2X7 receptor can mediate different inflammatory cells to mediate the progression of tissue-wide inflammation. At present, the role of P2X receptors in inflammatory response has been widely recognized and affirmed. Therefore, in this paper, we discussed the role of P2X receptors-mediated inflammation. Moreover, we also described the effects of some antagonists (such as A-438079, 5-BDBD, A-804598, A-839977, and A-740003) on inflammation relief by antagonizing the activities of P2X receptors.

Contribution of P2X purinergic receptor in cerebral ischemia injury.

The development of cerebral ischemia involves brain damage and abnormal changes in brain function, which can cause neurosensory and motor dysfunction, and bring serious consequences to patients. P2X purinergic receptors are expressed in nerve cells and immune cells, and are mainly expressed in microglia. The P2X4 and P2X7 receptors in the P2X purinergic receptors play a significant role in regulating the activity of microglia. Moreover, ATP-P2X purine information transmission is involved in the progression of neurological diseases, including the release of pro-inflammatory factors, driving factors and cytokines after cerebral ischemia injury, inducing inflammation, and aggravating cerebral ischemia injury. P2X receptors activation can mediate the information exchange between microglia and neurons, induce neuronal apoptosis, and aggravate neurological dysfunction after cerebral ischemia. However, inhibiting the activation of P2X receptors, reducing their expression, inhibiting the activation of microglia, and has the effect of protecting nerve function. In this paper, we discussed the relationship between P2X receptors and nervous system function and the role of microglia activation inducing cerebral ischemia injury. Additionally, we explored the potential role of P2X receptors in the progression of cerebral ischemic injury and their potential pharmacological targets for the treatment of cerebral ischemic injury.

SARS-CoV-2: Operating room management strategies and recommendations.

Since the outbreak of SARS-CoV-2/COVID-19 in Wuhan, China in 2019, it has rapidly spread to the world, and the number of infections has gradually increased. The hospitalization rate of patients has also gradually increased, which poses a huge challenge to hospitals and medical staff for patients with SARS-CoV-2 requiring surgical treatment. Therefore, avoiding cross-infection in the operating room is an important protective work. The operating room is an important department of the hospital, scientific and reasonable management is particularly important. Therefore, we have put forward corresponding suggestions and strategies for preoperative preparation and evaluation of patients, intraoperative management, postoperative terminal management, and protection of medical staff, and hope that these measures can better prevent and control the infection of SARS-CoV-2 in the operating room.

P2X7 receptor in inflammation and pain.

Different studies have confirmed P2X7 receptor-mediated inflammatory mediators play a key role in the development of pain. P2X7 receptor activation can induce the development of pain by mediating the release of inflammatory mediators. In view of the fact that P2X7 receptor is expressed in the nervous system and immune system, it is closely related to the stability and maintenance of the nervous system function. ATP activates P2X7 receptor, opens non-selective cation channels, activates multiple intracellular signaling, releases multiple inflammatory cytokines, and induces pain. At present, the role of P2X7 receptor in inflammatory response and pain has been widely recognized and affirmed. Therefore, in this paper, we discussed the pathological mechanism of P2X7 receptor-mediated inflammation and pain, focused on the internal relationship between P2X7 receptor and pain. Moreover, we also described the effects of some antagonists on pain relief by inhibiting the activities of P2X7 receptor. Thus, targeting to inhibit activation of P2X7 receptor is expected to become another potential target for the relief of pain.

Study of Trichostation A-Induced Expression of Costimulatory Molecules CD80 and CD86 in Acute Myelocytic Leukemia Cells.

OBJECTIVE: To investigate the trichostain A (TSA)-induced expression of costinmulatory molecules CD80 and CD86 in HL-60, K562 and mononuclear cells (MNC) of bone marrow in AML patients and its clinical significance. METHODS: The TSA-induced expression of costimulatory molecules CD80, CD86 in HL-60, K562 and BMMNC, and the cell viability were detected by flow cytometry; the mRNA expression of CD80 and CD86 was detected by RT-PCR; after the TSA-induced HL-60 cells and K562 cells were irradiated with 75 Gy, the effect of these cells on proliferation of PBMNC from healthy volunteers was determined with CCK-8 method. RESULTS: The HL-60 cells and BMMNC in AML patients expressed CD86, not expressed CD80, while the K562 cells not expressed CD86 and CD80. TSA could up-regulate the expression of CD86 in HL-60 cells and BMMNC of AML patients. The TSA-induced HL-60 cells expressing costimulatory molecule CD86 showed the proliferative effect on BMMNC from healthy volunteers. CONCLUSION: The TSA can induce the expression of costimulatory molecule CD86 in HL-60 cells and BMMNC in AML patients, and can improve the proliferation of PBMNC in healthy volunteers.