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.

The anti-inflammatory and immunomodulatory effects of olfactory ensheathing cells transplantation in spinal cord injury and concomitant pathological pain.

Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice.

Proteomics analysis of immune response-related proteins in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.

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.

STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression.

Objective: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway. Methods: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model. Results: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH. Conclusion: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.

3D printing redefines microneedle fabrication for transdermal drug delivery.

Microneedles (MNs) have emerged as an innovative, virtually painless technique for intradermal drug delivery. However, the complex and costly fabrication process has limited their widespread accessibility, especially for individuals requiring frequent drug administration. This study introduces a groundbreaking and cost-effective method for producing MNs utilizing fused deposition modeling (FDM) 3D printing technology to enhance transdermal drug delivery. The proposed fabrication process involves the elongation of molten polylactic acid (PLA) filaments to create meticulously designed conoid and neiloid MNs with smooth surfaces. This study underscores the critical role of printing parameters, particularly extrusion length and printing speed, in determining the shape of the MNs. Notably, the conoid-shaped MNs exhibit exceptional skin-penetrating capabilities. In order to evaluate their effectiveness, the MNs were tested on a polydimethylsiloxane (PDMS) skin model for skin penetration. The results highlight the high potential of 3D-printed MNs for transdermal drug administration. This novel approach capitalizes on the benefits of 3D printing technology to fabricate MNs that hold the promise of transforming painless drug administration for a variety of medical applications.

Prenatal ultrasonic diagnosis of esophageal atresia and tracheoesophageal fistula combined with interrupted inferior vena cava: a rare case report.

PURPOSE: This is an extremely rare case of complicated fetal esophageal atresia (EA) with tracheoesophageal fistula (TEF) and interrupted inferior vena cava (IVC) diagnosed by prenatal ultrsonography and successfully treated with surgical repair. METHODS: A 35-year-old pregnant woman was referred to our center for prenatal ultrasound, and the fetus was found to have a series of abnormalities, such as an interrupted IVC associated with a dilated azygos vein, an upper neck pouch sign of the thorax, and polyhydramnios. With suspicion of EA with TEF and interrupted IVC, the infant was born at 39 weeks of gestation, and successfully underwent the surgical operation. RESULTS: The baby was doing well after 21 months of follow-up. CONCLUSION: It is beneficial for the prenatal ultrasonic diagnosis of EA with TEF in optimizing labor care, postpartum treatment, and prompting neonatal management.

Patterns and correlates of potential range shifts of bat species in China in the context of climate change.

Climate change may diminish biodiversity; thus, it is urgent to predict how species' ranges may shift in the future by integrating multiple factors involving more taxa. Bats are particularly sensitive to climate change due to their high surface-to-volume ratio. However, few studies have considered geographic variables associated with roost availability and even fewer have linked the distributions of bats to their thermoregulation and energy regulation traits. We used species distribution models to predict the potential distributions of 12 bat species in China under current and future greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5) and examined factors that could affect species' range shifts, including climatic, geographic, habitat, and human activity variables and wing surface-to-mass ratio (S-MR). The results suggest that Ia io, Rhinolophus ferrumequinum, and Rhinolophus rex should be given the highest priority for conservation in future climate conservation strategies. Most species were predicted to move northward, except for I. io and R. rex, which moved southward. Temperature seasonality, distance to forest, and distance to karst or cave were the main environmental factors affecting the potential distributions of bats. We found significant relationships between S-MR and geographic distribution, current potential distribution, and future potential distribution in the 2050s. Our work highlights the importance of analyzing range shifts of species with multifactorial approaches, especially for species traits related to thermoregulation and energy regulation, to provide targeted conservation strategies.

Patrones y correlaciones de los cambios potenciales en la distribución de las especies de murciélago de China en el contexto del cambio climático Resumen El cambio climático puede disminuir la biodiversidad, por lo que es urgente pronosticar cómo puede cambiar en el futuro la distribución de las especies mediante la integración de múltiples factores que involucren a más taxones. Los murciélagos son particularmente sensibles al cambio climático debido a que tienen una gran proporción superficie­volumen. Sin embargo, hay pocos estudios que han considerado las variables asociadas con la disponibilidad de nidos y son todavía menos los que han conectado la distribución de los murciélagos con sus rasgos de termorregulación y regulación de energía. Usamos modelos de distribución de especies para pronosticar la distribución potencial de doce especies de murciélago en China bajo escenarios actuales y futuros de emisión de gases de efecto invernadero (SSP1­2.6 y SSP5­8.5) y analizamos los factores que podrían afectar el cambio en la distribución de las especies, incluyendo las variables climáticas, geográficas, de hábitat y de actividad humana y la proporción entre la superficie del ala y la masa (P S­M). Los resultados sugieren que Ia io, Rhinolophus ferrumequinum y R. rex deberían ser la mayor prioridad de conservación para las estrategias de conservación climáticas en el futuro. Pronosticamos que la mayoría de las especies se desplazarían al norte, a excepción de I. io y R. rex, que se desplazarían hacia el sur. Los principales factores que afectaron la distribución potencial de los murciélagos fueron la estacionalidad de la temperatura, la distancia al bosque y la distancia a la cueva o al karst. Encontramos una relación significativa entre la P S­M y la distribución geográfica, la distribución potencial actual y la distribución potencial para la década de 2050. Nuestra investigación destaca la importancia del análisis de los cambios de distribución de las especies con enfoques multifactoriales, especialmente para los rasgos de especie relacionados con la termorregulación y la regulación de energía, para proporcionar estrategias de conservación focalizadas.

Protective effects of the secondary metabolites from Quercus salicina Blume against gentamicin-induced nephrotoxicity in zebrafish (Danio rerio) model.

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney.

Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy.

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, ß-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, ß-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Clinical and economic comparison of laparoscopic versus open hepatectomy for primary hepatolithiasis: a propensity score-matched cohort study.

BACKGROUND: It is unclear whether laparoscopic hepatectomy (LH) for hepatolithiasis confers better clinical benefit and lower hospital costs than open hepatectomy (OH). This study aim to evaluate the clinical and economic value of LH versus OH. METHODS: Patients undergoing OH or LH for primary hepatolithiasis at Yijishan Hospital of Wannan Medical College between 2015 and 2022 were divided into OH group and LH group. Propensity score matching (PSM) was used to balance the baseline data. Deviation-based cost modelling and weighted average median cost (WAMC) were used to assess and compare the economic value. RESULTS: A total of 853 patients were identified. After exclusions, 403 patients with primary hepatolithiasis underwent anatomical hepatectomy (OH n=143; LH n=260). PSM resulted in 2 groups of 100 patients each. Although LH required a longer median operation duration compared with OH (285.0 versus 240.0 min, respectively, P<0.001), LH patients had fewer wound infections, fewer pre-discharge overall complications (26 versus 43%, respectively, P=0.009), and shorter median postoperative hospital stays (8.0 versus 12.0 days, respectively, P<0.001). No differences were found in blood loss, major complications, stone clearance, and mortality between the two matched groups. However, the median overall hospital cost of LH was significantly higher than that of OH (CNY¥52,196.1 versus 45,349.5, respectively, P=0.007). Although LH patients had shorter median postoperative hospital stays and fewer complications than OH patients, the WAMC was still higher for the LH group than for the OH group with an increase of CNY¥9,755.2 per patient undergoing LH. CONCLUSION: The overall clinical benefit of LH for hepatolithiasis is comparable or even superior to that of OH, but with an economic disadvantage. There is a need to effectively reduce the hospital costs of LH and the gap between costs and diagnosis-related group reimbursement to promote its adoption.

The functional role of P2 purinergic receptors in the progression of gastric cancer.

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

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.

Olfactory ensheathing cells as candidate cells for chronic pain treatment.

Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.

The impact of the P2X7 receptor on the tumor immune microenvironment and its effects on tumor progression.

Cancer is a significant global health concern, and finding effective methods to treat it has been a focus of scientific research. It has been discovered that the growth, invasion, and metastasis of tumors are closely related to the environment in which they exist, known as the tumor microenvironment (TME). The immune response interacting with the tumor occurring within the TME constitutes the tumor immune microenvironment, and the immune response can lead to anti-tumor and pro-tumor outcomes and has shown tremendous potential in immunotherapy. A channel called the P2X7 receptor (P2X7R) has been identified within the TME. It is an ion channel present in various immune cells and tumor cells, and its activation can lead to inflammation, immune responses, angiogenesis, immunogenic cell death, and promotion of tumor development. This article provides an overview of the structure, function, and pharmacological characteristics of P2X7R. We described the concept and components of tumor immune microenvironment and the influence immune components has on tumors. We also outlined the impact of P2X7R regulation and how it affects the development of tumors and summarized the effects of drugs targeting P2X7R on tumor progression, both past and current, assisting researchers in treating tumors using P2X7R as a target.

Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury.

BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.

The role of olfactory ensheathing cells in the repair of nerve injury.

Cell transplantation has brought about a breakthrough in the treatment of nerve injuries, and the efficacy of cell transplantation compared to drug and surgical therapies is very exciting. In terms of transplantation targets, the classic cells include neural stem cells (NSCs) and Schwann cells, while a class of cells that can exist and renew throughout the life of the nervous system - olfactory ensheathing cells (OECs) - has recently been discovered in the olfactory system. OECs not only encircle the olfactory nerves but also act as macrophages and play an innate immune role. OECs can also undergo reprogramming to transform into neurons and survive and mature after transplantation. Currently, many studies have confirmed the repairing effect of OECs after transplantation into injured nerves, and safe and effective results have been obtained in clinical trials. However, the specific repair mechanism of OECs among them is not quite clear. For this purpose, we focus here on the repair mechanisms of OECs, which are summarized as follows: neuroprotection, secretion of bioactive factors, limitation of inflammation and immune regulation, promotion of myelin and axonal regeneration, and promotion of vascular proliferation. In addition, integrating the aspects of harvesting, purification, and prognosis, we found that OECs may be more suitable for transplantation than NSCs and Schwann cells, but this does not completely discard the value of these classical cells. Overall, OECs are considered to be one of the most promising transplantation targets for the treatment of nerve injury disorders.

Application and challenges of olfactory ensheathing cells in clinical trials of spinal cord injury.

Spinal cord injury (SCI) can lead to severe motor, sensory and autonomic nervous dysfunction, cause serious psychosomatic injury to patients. There is no effective treatment for SCI at present. In recent years, exciting evidence has been obtained in the application of cell-based therapy in basic research. These studies have revealed the fact that cells transplanted into the host can exert the pharmacological properties of treating and repairing SCI. Olfactory ensheathing cells (OECs) are a kind of special glial cells. The application value of OECs in the study of SCI lies in their unique biological characteristics, that is, they can survive and renew for life, give full play to neuroprotection, immune regulation, promoting axonal regeneration and myelination formation. The function of producing secretory group and improving microenvironment. This provides an irreplaceable treatment strategy for the repair of SCI. At present, some researchers have explored the possibility of treatment of OECs in clinical trials of SCI. Although OECs transplantation shows excellent safety and effectiveness in animal models, there is still lack of sufficient evidence to prove the effectiveness of their clinical application in clinical trials. There has been an obvious stagnation in the transformation of OECs transplantation into routine clinical practice, and clinical trials of cell therapy in this field are still facing major challenges and many problems that need to be solved. Therefore, this paper summarized and analyzed the clinical trials of OECs transplantation in the treatment of SCI, and discussed the problems and challenges of OECs transplantation in clinical trials.

P2 purinergic receptors regulate the progression of colorectal cancer.

More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.