Heme oxygenase 1 (HO1) regulates autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway of yak Sertoli cells.

Successful male reproduction depends on healthy testes. Autophagy has been confirmed to be active during many cellular events associated with the testes. It is not only crucial for testicular spermatogenesis but is also an essential regulatory mechanism for Sertoli cell (SCs) ectoplasmic specialization integrity and normal function of the blood-testis-barrier. Hypoxic stress induces oxidative damage, apoptosis, and autophagy, negatively affecting the male reproductive system. Cryptorchidism is a common condition associated with infertility. Recent studies have demonstrated that hypoxia-induced miRNAs and their transcription factors are highly expressed in the testicular tissue of infertile patients. Heme oxygenase 1 (HO1) is a heat-shock protein family member associated with cellular antioxidant defense and anti-apoptotic functions. The present study found that the HO1 mRNA and protein are up-regulated in yak cryptorchidism compared to normal testes. Next, we investigated the expression of HO1 in the SCs exposed to hypoxic stress and characterized the expression of key molecules involved in autophagy and apoptosis. The results showed that hypoxic stress induced the upregulation of autophagy of SCs. The down-regulation of HO1 using siRNA increases autophagy and decreases apoptosis, while the over-expression of HO1 attenuates autophagy and increases apoptosis. Furthermore, HO1 regulates autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway. These results will be helpful for further understanding the regulatory mechanisms of HO1 in yak cryptorchidism.

Clinical report of microsurgical treatment of Kohler's disease.

The conservative treatment for Kohler's disease will take several months, but some patients still have flatfoot and persistent pain. From October 2013 to July 2015, 3 children with Kohler's disease underwent navicular decompression and micro-circulation reconstruction surgery in our hospital. All the patients have received conservative treatment for more than 3 months and the effect was poor. X-ray showed the bone density of navicular increased significantly. All patients were followed up over 1 year. The 3 patients recovered well. VAS score decreased from 7.0 to 2.6 at 1 month after the operation. The pain symptom disappeared completely on 3 months after surgery. The density of navicular bone recovered to normal. Navicular decompression and micro-circulation reconstruction surgery may quickly improve the ischemic status of navicular bone, alleviate pain symptom and enable patients to resume normal activity as soon as possible.

Use total portosystemic shunt to rescue an emergency PNF with intractable hypotension: A case report.

RATIONALE: Living donor allogeneic liver transplantation is a surgical treatment for patients with end-stage liver disease, wherein a healthy liver is implanted in the patient, facilitating the recovery of the liver function in patients with end-stage liver disease. However, primary nonfunction (PNF) may occur as a result of this procedure. PATIENT CONCERNS: A case of an 65-year-old Asian male with a medical history of cirrhosis and hepatocellular carcinoma is described. Intractable hypotension occurred after open hepatic portal anastomosis, and large doses of vasoactive substances did not improve the condition. DIAGNOSIS: PNF was diagnosed during surgery and it caused intractable hypotension. INTERVENTIONS: we promptly used the total portosystemic shunt to achieve a successful rescue. OUTCOMES: The strengthening of perioperative management and active treatment allowed second liver transplantation and anhepatic phase of up to 10 hours, following which the patient was rescued. LESSONS: The lesson we have learned is that total portosystemic shunt composited with careful anesthesia management can rescue the event of PNF with intractable hypotension in liver transplantation surgery. At the same time, we give attention to blood pressure, electrocardiogram, albumin, calcium, potassium, acidosis, coagulopathy, anti-infection, and protection of vital organs is essential for successful retransplant outcomes.

Synthesis, biological activity evaluation and mechanism analysis of new ganglioside GM3 derivatives as potential agents for nervous functional recovery.

Neuronal regenerative ability is vital for the treatment of neurodegenerative diseases and neuronal injuries. Recent studies have revealed that Ganglioside GM3 and its derivatives may possess potential neuroprotective and neurite growth-promoting activities. Herein, six GM3 derivatives were synthesized and evaluated their potential neuroprotective effects and neurite outgrowth-promoting activities on a cellular model of Parkinson's disease and primary nerve cells. Amongst these derivatives, derivatives N-14 and 2C-12 demonstrated neuroprotective effects in the MPP + model in SH-SY5Y cells. 2C-12 combined with NGF (nerve growth factor) induced effecially neurite growth in primary nerve cells. Further action mechanism revealed that derivative 2C-12 exerts neuroprotective effects by regulating the Wnt signaling pathway, specifically involving the Wnt7b gene. Overall, this study establishes a foundation for further exploration and development of GM3 derivatives with neurotherapeutic potential.

Uterine giant cell tumor of soft tissue: A case report.

INTRODUCTION: Giant cell tumor of soft tissue (GCT-ST) is a rare primary soft tissue tumor. GCT-ST mainly occurs in the trunk and extremities. There is no standard treatment for GCT-ST. This paper reports a rare case of primary uterine GCT-ST. CASE PRESENTATION: A 48-year-old female patient underwent a transabdominal subhysterectomy for uterine leiomyoma. Postoperative pathological examination showed GCT-ST with unclear tissue boundary (10.0 × 6.0 × 5.0 cm). A small amount of GCT-ST tissue could be seen on the local edge of the leiomyoma. Residual tumor tissue was found around the uterine cavity. The patient reported persistent lower abdominal distension pain 3 months after the operation. Pelvic and abdominal imaging showed a huge tumor and multiple pelvic and abdominal organ metastasis. No pulmonary metastasis was found. Exploratory surgery revealed widespread metastases in the abdominal and peritoneal cavities, involving both ovaries, right tubal serous membrane, appendix serous membrane, bladder, pelvic peritoneum, and abdominal wall incision. After surgery, the patient had 6 cycles of docetaxel and carboplatin but stopped treatments due to economic reasons. The patient died 3 months later because of multiple organs failure. CONCLUSION: GCT-ST is generally benign but has unpredictable behavior. A massive recurrence with wide invasion is possible after subtotal resection.

Establishment of a prognostic model for melanoma based on necroptosis-related genes.

In this study, the clinical implications and potential functions of necroptosis-related genes (NRGs) in melanoma were systematically characterized. A novel NRG signature was then constructed to analyze the immune status and prognosis of patients with melanoma. The NRG signatures for melanoma prognosis were searched using the Cancer Genome Atlas (TCGA) dataset and followed by stepwise Cox regression analysis. Patients with melanoma were divided into two groups, and survival analysis, receiver operating characteristic (ROC), and univariate and multivariate analyses were subsequently performed. The correlation of risk score (RS) with tumor immunity and RT-polymerase chain reaction (PCR) was analyzed to further verify the gene signatures. Data on tumor mutational burden (TMB) and chromosomal copy number variation (CNV) were analyzed. Three NRGs were identified as prognostic risk signatures and were significantly related to overall survival (OS) in melanoma. The signatures had better diagnostic accuracy. Furthermore, analysis of mutations in the NRGs and the incidence of chromosomal CNV helped to reveal the relationship between mutations and melanoma occurrence. A nomogram was established based on RSs. The risk characteristics were significantly associated with immunity and high risk is closely correlated with melanoma development. In vitro experiments revealed that necrostatin-1 (Nec-1) promoted cell viability and repressed the expression levels of interleukin (IL)12A and proprotein convertase subtilisin/kexin type (PCSK)1. Additionally, the expression levels of IL12A, CXCL10, and PCSK1 decreased in tumor tissues of melanoma patients. NRGs exert vital roles in immunity and might be applied as a prognostic factor of melanoma.

Partial talar replacement with a novel 3D printed prosthesis.

BACKGROUND: The treatment of talus avascular necrosis (AVN) is challenging owing to its unique anatomical features. Despite decades of studies, till date, there is no appropriate treatment for talus AVN. Therefore, surgeons need to develop newer surgical methods. In the present study we introduce a new surgical method, 3D printed partial talus replacement (PTR), to treat partial talus necrosis and collapse (TNC). METHODS: A male patient with talus AVN underwent PTR in our hospital. The morphology of the talus was quantified using 3D computed tomography (CT) imaging. A novel 3D printed titanium prothesis was designed and manufactured according to the findings of the CT imaging. The prosthesis was applied during talus replantation surgery to reconstruct the anatomical structure of the ankle. The follow-up period for this patient was 24 months. The visual analog scale (VAS) scores before and after surgery, American Orthopedic Foot and Ankle Score (AOFAS), ankle range of motion, and postoperative complications were recorded to evaluate the prognosis. RESULTS: The anatomical structure of the talus was reconstructed. The patient was satisfied with the effects of treatment, recovery, and function. The VAS score decreased from 5 to 1. The AOFAS improved from 70 to 93. The range of motion remained the same as that during the pre-operation. The patient returned to a normal life. CONCLUSION: 3D printed PTR is a new surgical method for talus AVN that can provide satisfactory outcomes. In future, PTR might be an effective and preferential treatment for the treatment of partial talus AVN and collapse.

Necroptosis-Related LncRNA Signatures for Prognostic Prediction in Uterine Corpora Endometrial Cancer.

Necroptosis is one of the common modes of apoptosis, and it has an intrinsic association with cancer prognosis. However, the role of the necroptosis-related long non-coding RNA LncRNA (NRLncRNAs) in uterine corpora endometrial cancer (UCEC) has not yet been fully elucidated at present. Therefore, the present study is designed to investigate the potential prognostic value of necroptosis-related LncRNAs in UCEC. In the present study, the expression profiles and clinical data of UCEC patients were downloaded from TCGA database to identify the differentially expressed NRLncRNAs associated with overall survival. A LncRNA risk model was constructed via Cox regression analysis, and its prognostic value was evaluated. We have also further evaluated the relationships between the LncRNA features and the related cellular function, related pathways, immune status, and immune checkpoints m6A-related genes. Seven signatures, including PCAT19, CDKN2B-AS1, LINC01936, LINC02178, BMPR1B-DT, LINC00237, and TRPM2-AS, were established to assess the overall survival (OS) of the UCEC in the present study. Survival analysis and ROC curves indicated that the correlated signature has good predictable performance. The normogram could accurately predict the overall survival of the patients with an excellent clinical practical value. Enrichment analysis of gene sets indicated that risk signals were enriched in several immune-related pathways. In addition, the risk characteristics were significantly correlated with immune cells, immune function, immune cell infiltration, immune checkpoints, and some m6A-related genes. This study has identified seven necroptosis-related LncRNA signatures for the first time, providing a valuable basis for a more accurate prognostic prediction of UCEC.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Bushen Hugu Decoction in the Treatment of Malignant Tumor Bone Metastases.

Purpose: To explore the active compounds of the Chinese medicine prescriptions of Bushen Hugu Decoction (BHD) and demonstrate its mechanisms against malignant tumor bone metastasis (BM) through network pharmacology and molecular docking analysis. Methods: The main components and targets of BHD were retrieved from the TCMSP database, and the targets were normalized by UniProt. The Herbs-Components-Targets network of BHD was established by Cytoscape. The main BM targets were obtained from GeneCards, TTD, DrugBank, and OMIM. STRING and Cytoscape were used to construct a PPI network and obtain hub genes. DAVID and Metascape were used for GO and KEGG enrichment analyses. According to the network topology parameters, the top 4 components were selected for molecular docking verification with the core targets. Results: Compound-target network of BHD mainly contained 51 compounds and 259 corresponding targets including 107 BHD-BM targets. PPI interaction network and subnetworks identified ten hub genes. GO enrichment analysis found 1970 terms (p < 0.05), and 164 signaling pathways (p < 0.05) were found in KEGG, including PI3K-Akt signaling pathway, proteoglycans in cancer, prostate cancer, MAPK signaling pathway, and IL-17 signaling pathway. Molecular docking analysis showed that the active components of BHD, quercetin, luteolin, kaempferol, and aureusidin have good binding activity to the core targets. Conclusion: The potential molecular target and signaling pathways were found for BHD major active components. It provides guidance for the future mechanism research of the BHD in malignant tumor bone metastasis. This study also established the foundation for the new strategy for the pharmacology study of Chinese medicine.

Long-term outcomes of toe replantation: A review of ten cases.

BACKGROUND: Foot injuries due to vehicular or other accidents are common. However, complete toe amputation is rare. This study explored the current protocols and clinical significance of toe replantation. METHODS: From December 2011 to December 2018, ten patients with 13 severed toes underwent toe replantation in our hospital. Seven cases were replanted antegrade, and three cases were replanted retrograde. RESULTS: All patients were followed for two to three years after toe replantation. One big toe underwent necrosis, while the other 12 toes survived completely. The appearance and feel of the successfully replanted toes were satisfactory, and the patients exhibited a normal gait. CONCLUSION: Toe replantation can achieve an acceptable appearance and function of the foot and considerably reduce the psychological effects experienced by the patients. Increased clinical attention and application of toe replantation are needed. LEVEL OF EVIDENCE: Level IV, retrospective case series.

The oncological and obstetric results of radical trachelectomy as a fertility-sparing therapy in early-stage cervical cancer patients.

PURPOSE: This study explored the oncological and obstetric results of radical trachelectomy (RT) in early-stage cervical cancer patients. METHODS: A retrospective analysis was conducted the oncological and obstetric results of 23 patients with early cervical cancer (stages IA2-IB3; International Federation of Gynecology and Obstetrics, 2018) who underwent RT in The Maternal and Child Health Care Hospital of Guiyang, China, from October 2004 to September 2018. RESULTS: 23 patients had cervical tumors of the squamous cell carcinoma histological type. All 23 patients retained reproductive function. The mean follow-up time was 112.87 ± 55.75 (36-199) months. The median tumor size was 2.00 ± 1.35 cm (imperceptible to the eyes 5.00 cm). No recurrence was observed in any of the patient cases. Among the patients with a tumor size > 4 cm (up to 5 cm), three patients who wished to preserve fertility accepted RT following neoadjuvant chemotherapy The pregnancy outcomes were as follows: 8 cases (47.06%) out of 17 cases who attempting pregnancy conceived 12 times.First-trimester abortion and the voluntary abandonment of pregnancy occurred in 4 cases (33.33%), respectively, one patient performed deliberate termination at 24 weeks of gestation. Second-trimester abortion occurred in three cases (25.0%) for chorioamnionitis. Premature delivery at 32 weeks occurred in one case (8.33%). CONCLUSION: Radical trachelectomy is a safe and effective treatment for women with early-stage cervical cancer preserving fertility biology. Patients with a cervical tumor sized > 4 cm can be pregnant after neoadjuvant chemotherapy and RT. Accordingly, this treatment is worthy of further exploration.

Effect and mechanisms of kaempferol against endometriosis based on network pharmacology and in vitro experiments.

Endometriosis is a common gynecological disease, and its underlying mechanisms remain elusive. Patients are at a higher risk of recurrence after surgery or drug withdrawal. In this study, to identify a potentially effective and safe therapy for endometriosis, we screened potential target genes of kaempferol on endometriosis using network pharmacology and further validation. Network pharmacology showed kaempferol may suppress migratory and invasive properties by modulating the phosphoinositide 3-kinase (PI3K) pathway and its downstream target matrix metalloproteinase (MMP)9. Furthermore, in vitro experiments showed that kaempferol repressed the migration and invasion of endometrial cells, and this effect may be involved in mediating the PI3K-related genes, phosphatase and tensin homolog (PTEN) and MMP9. Network pharmacology and in vitro experiments showed that kaempferol, repressed the implantation of endometrial cells and formation of ectopic lesions by inhibiting migration and invasion and regulating PTEN and MMP9, which may be associated with the PI3K pathway.

Amino-functionalized hypercrosslinked polymer as sorbent for effective extraction of nitroimidazoles from water, drink and honey samples.

The three hypercrosslinked polymers (HCP) materials, designated as OPD-HCP, MPD-HCP and PPD-HCP, were synthesized by using o-phenylenediamine (OPD), m-phenylenediamine (MPD) and p-phenylenediamine (PPD) as monomers. They were characterized by infrared spectroscopy, powder X-ray diffraction, nitrogen sorption isotherms, and scanning electron microscopy. Then, the HCPs were explored as solid-phase extraction (SPE) adsorbent for the extraction of five nitroimidazoles (NDZs) (metronidazole, ronidazole, secnidazole, dimetridazole and ornidazole). Among the three HCPs, the MPD-HCP has the best adsorption performance for the NDZs. With the help of high-performance liquid chromatography with ultraviolet detection (HPLC-UV), good linear response range (0.07-40.0 ng mL-1), high method recovery (86.8%-113.3%), low limits of detection (0.02-0.15 ng mL-1) and good precision with the relative standard deviations of less than 8.1% were achieved for the determination of the NDZs in water samples. The effective determination of the NDZs in peach juice, honey tea, and honey samples were also realized by the developed method with satisfactory results. Based on both the experimental results and density functional theory calculation, the adsorption mechanism can be attributed to multiple interactions between the MPD-HCP and the NDZs, including hydrogen bonding, hydrophilic, and electrostatic interactions. The method provides a new alternative of choice for the determination of some NDZs in real samples.

Application of cryopreserved autologous skin replantation in the treatment of degloving injury of limbs.

Degloving injury is a common and intractable injury with the bone and tendon exposed and contamination, the stripped skin cannot be replanted immediately and will be discarded, although auto-graft is needed for subsequent wound repair. In this study, autologous skin cryopreservation technique was applied to the treatment of severe limb degloving injuries. The clinical data of 9 patients from January 2016 to December 2018 were analyzed retrospectively. Among the 9 cases, 1 case developed necrosis due to wound infection, and the rest survived 60-100%. The replanted cryopreserved skin were soft and resilient, with poor sensory recovery, varying degrees of discoloration and no hair growth. Cryopreservation provides more time for improving the wound and whole-body condition. The frozen skin had good quality and high survival rate. Our study can effectively use the degloving skin, reduce the damage of the donor area.

One-Pot Enzymatic Synthesis and Biological Evaluation of Ganglioside GM3 Derivatives as Potential Cancer Immunotherapeutics.

Cancer is a leading cause of death worldwide. Recent research studies have revealed that GM3 derivatives have considerable promise as potential therapeutic agents for cancer. To discover novel GM3 derivatives as potential antitumor agents, a one-pot enzymatic synthesis was established, yielding 14 GM3 derivatives in high total yields (22-41%). Subsequently, the inhibitory activities of GM3 derivatives were assessed by wound-healing assays and Transwell assays and tumor-bearing animal models. Among all the GM3 derivatives, N-12 showed excellent migration and invasion inhibitory effects in cells and marked antitumor activity in C57BL/6 mice. The subsequent analysis of cancer tissues and serum samples revealed that N-12 induces tumor inhibition, which was closely related to immune response. Taken together, N-12 can be further developed as an effective therapeutic for the treatment of cancer. An RNA-sequencing (RNA-seq) analysis was then performed and indicated that the antitumor mechanism of N-12 involved focal adhesion and ECM-receptor interaction signaling pathways.

Perfluorooctane sulfonate (PFOS) triggers migration and invasion of esophageal squamous cell carcinoma cells via regulation of Zeb1.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly cancers worldwide, especially in Eastern Asia. As a potential endocrine-disrupting chemical (EDC), perfluorooctane sulfonate (PFOS) can mimic estrogen, disturb the estrogen signals, and then cause various diseases. Although ESCC can be directly exposed to PFOS during food digestion, the effects and mechanisms of PFOS on the development of ESCC are still not well illustrated. This study showed that PFOS can promote the migration and invasion of ESCC cells. Further, PFOS treatment can increase the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while decreasing the expression of E-Cadherin (E-Cad). Zeb1, an important transcription factor for cell motility, was essential for PFOS induced migration and invasion of ESCC cells. PFOS can increase the expression of Zeb1 via upregulation of its transcription and proteins stability. A-kinase interacting protein 1 (AKIP1) and ataxia-telangiectasia mutated (ATM) were responsible for PFOS induced transcription and proteins stability of Zeb1 in ESCC cells, respectively. Collectively, our data indicated that environmental exposure and body accumulation of PFOS might be an important risk factor for ESCC progression.

Discovery of Sortase A covalent inhibitors with benzofuranene cyanide structures as potential antibacterial agents against Staphylococcus aureus.

Sortase A (SrtA) is a cysteine transpeptidase of most gram-positive bacteria that is responsible for the anchoring of many surface protein virulence factors to the cell wall. SrtA ablation has demonstrated to alleviate the infection without affecting the viability of bacteria. Herein, a series of benzofuran cyanide derivatives were synthesized and evaluated. Several compounds exhibited excellent inhibitory activity against SrtA with IC50 values from 3.3 µM to 21.8 µM compared with the known SrtA inhibitor pHMB (IC50 = 130 µM). Ⅲ-1, Ⅲ-15, Ⅲ-34 and V-1 showed potent inhibitory effects on biofilm formation with IC50 values from 2.1 µM to 54.2 µM. Invasion assays showed the four compounds caused a decrease of 4%-24.0% in the uptake of the S. aureus strain by 293T cells. Further assay showed that compound Ⅲ-15 decreased the amount of cell wall-associated protein A by 26.5%. Structure-activity relationship and docking studies demonstrated that the acrylonitrile moiety of the compounds played an important role in enhancing the activity. When the double bond of acrylonitrile changed to single bond, the activity was decreased significantly. This indicates that acrylonitrile, which is a Michael receptor, can inhibit the activity of SrtA by covalent binding effectively to the thiol group of Cys184.

Predictive value of neurophysiological monitoring during posterior communicating artery aneurysm clipping for postoperative neurological deficits.

Objective: This study aimed to evaluate the diagnostic effect of intraoperative neurophysiological monitoring in identifying intraoperative ischemic events and predicting postoperative neurological dysfunction during PCoA aneurysm clipping, as well as to explore the safe duration of intraoperative temporary clipping of the parent artery. Methods: All 71 patients with PCoA aneurysm underwent craniotomy and aneurysm clipping. MEP and SSEP were used for monitoring during operation to evaluate the influence of MEP/SSEP changes on postoperative neurological function. Receiver operating characteristic (ROC) curve analysis was used to calculate optimal duration of intraoperative temporary clipping. Results: Patients with intraoperative MEP/SSEP changes were more likely to develop short-term and long-term neurological deficits than those without MEP/SSEP changes (P < 0.05). From the ROC curve analysis, the safe time from the initiation of temporary clipping during the operation to the early warning of neurophysiological monitoring was 4.5 min (AUC = 0.735, 95%CI 0.5558-0.912). Taking 4.5 min as the dividing line, the incidence of short-term and long-term neurological dysfunction in patients with temporary clipping >4.5 min was significantly higher than that in patients with temporary clipping ≤4.5 min (P = 0.015, P = 0.018). Conclusion: Intraoperative MEP/SSEP changes are significantly associated with postoperative neurological dysfunction in patients with PCoA aneurysms. The optimal duration of temporary clipping of the parent artery during posterior communicating aneurysm clipping was 4.5 min under neurophysiological monitoring.

An efficient method to identify virus-specific TCRs for TCR-T cell immunotherapy against virus-associated malignancies.

Adoptive transfer of T cells genetically engineered with a T cell receptor (TCR) is a promising cancer treatment modality that requires the identification of TCRs with good characteristics. Most T cell cloning methods involve a stringent singularization process, which necessitates either tedious hands-on operations or high cost. We present an efficient and nonstringent cloning approach based on existing techniques. We hypothesize that after elimination of most nonspecific T cells, a clonotype with high quality could outcompete other clonotypes and finally form a predominant population. This TCR identification method can be used to clone virus-specific TCRs efficiently from cancer patients and is easily adoptable by any laboratory.

Antinociceptive Effect of Magnolol in a Neuropathic Pain Model of Mouse.

BACKGROUND AND OBJECTIVE: Neuropathic pain remains a clinical challenge with limited effective treatments. Previous studies have found that magnolol (Mag), an ingredient existing in some herbs, showed neuroprotective effect. However, it remains unclear whether Mag can alleviate neuropathic pain. METHODS: Chronic constriction injury (CCI) is used as the neuropathic pain model. Mice were randomly divided into 5 groups: Sham, CCI, CCI + 5, 10, 30 mg/kg Mag groups. Thermal and mechanical paw withdrawal threshold were performed at baseline and on the 3rd, 5th, 7th, 14th days post-surgery. Lumbar spinal cord and blood samples were collected on the 14th day. Blood lipid profile, kidney and liver functions, as well as the activation of microglia were evaluated, along with the related signal pathway examined using multiple methods including immunohistochemistry, RT-PCR and Western blot. RESULTS: Mag alleviated thermal and mechanical hypersensitivity in CCI mice. CCI activated microglia and upregulated the expression of P2Y12, while Mag inhibited microglial activation, and downregulated the expression of P2Y12. Mag also blocked the activation of p38 mitogen-activated protein kinase (MAPK) and other pain-related cytokines such as IL-6, TNF-α and IL-1ß. CONCLUSION: The findings indicate that Mag has antinociceptive effect on neuropathic pain, probably mediated through P2Y12 receptors and p38 MAPK mediated pathways. With its relatively safe profile, Mag may be a potential therapeutic agent for neuropathic pain.