Identification of lymph node adulteration in minced pork by comprehensive metabolomics and lipidomics approach based on UPLC/LTQ-Orbitrap MS.

The deliberate pork adulteration with lymph nodes is a common adulteration phenomenon, and it poses a serious threat to public health and food safety. An untargeted metabolomics and lipidomics approach based on ultrahigh performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap high resolution mass spectrometry (MS) was used to distinguish lymph nodes from minced pork. The principal component analysis and orthogonal projection to latent structures discriminant analysis models were established with the good of fitness and predictivity. The results showed that there were significant differences in metabolites and lipids between lymph nodes and pork. A total of 16 significantly differentiated metabolites were identified, of which 1-palmitoylglycerophosphocholine, 12,13-dihydroxy-9-octadecenoic acid, and prostaglandin E2 (PGE2) were positively correlated with lymph node content and were identified as potential markers of lymph nodes. These three markers were combined to create a binary logistic regression model, and a combined-factor exceeding 0.75 was ultimately identified as a marker for pork adulteration with lymph nodes. The desorption electrospray ionization-MS images showed that PGE2 had a higher relative abundance in the lymph node region than in adjacent non-lymph node regions, indicating that PGE2 was a marker that contributed significantly for identifying lymph nodes adulteration into pork. Our results provide a theoretical basis for identifying lymph node adulteration, which will contribute to combating fraud in the meat industry.

Autophagy impairment is involved in midazolam-induced lipid droplet accumulation and consequent phagocytosis decrease in BV2 cells.

An increasing number of experimental and clinical observation suggest that the use of anaesthetics is closely associated with postoperative central nervous system (CNS) complications, such as delirium and cognitive dysfunction. Brain energy rescue is an emerging therapeutic strategy for central nervous system disease (CNSDs). However, the effect of anaesthetics on nerve cell energy utilisation, especially microglia, and its potential effects on cell function still unclear. Elucidating the effects of anaesthetics on lipid droplets, which are specific lipid storage organs, and phagocytosis of microglia is crucial to discover a new therapeutic concept for postoperative CNS complications. Here, we studied the effects of the commonly used anaesthetic midazolam on lipid droplets and phagocytosis in immortalised microglial BV2 cells. Lipid droplets were assessed by flow cytometry and triglyceride quantification. The phagocytosis of BV2 cells was evaluated by detecting their phagocytosis by latex beads. Additionally, the autophagy of BV2 cells was evaluated by western blot and observation under microscopy. Our results showed that midazolam caused lipid droplet accumulation and reduced phagocytosis in BV2 cells, and inhibition of lipid droplet accumulation partially restored phagocytosis. Furthermore, midazolam blocks autophagic degradation by increasing phosphorylated TFEB in BV2 cells, inhibition of midazolam-increased phosphorylated TFEB might contribute to the improvement of autophagic flux by rapamycin. Moreover, promoting autophagy reverse the lipid droplet accumulation and phagocytosis decrease. This study suggests autophagy is a target for attenuating lipid droplet accumulation, normal degradation of lipid droplets is important for maintaining microglia phagocytosis and attenuating the side effects of midazolam on the CNS.

Papillary Thyroid Carcinoma With Breast and Bone Metastasis.

Papillary thyroid carcinoma is the most common thyroid malignant tumor and usually has a fine prognosis. The most common metastatic site is the cervical lymph node, and distant metastasis is rare. This report describes a female patient with papillary thyroid carcinoma who presented with multiple metastases in the cervical lymph nodes, breast, and spine. The patient's disease course lasted 11 years, and eventually metastatic cancer led to the patient's death. We also analyzed the survival rate and median survival time of papillary thyroid carcinoma with multiple organ metastases using data in the literature.

CT findings of Talaromyces marneffei infection among HIV patients with lymphadenopathy.

Background: Talaromyces marneffei (T. marneffei) is an opportunistic fungal pathogen commonly found in human immunodeficiency virus (HIV) patients that often infects lymph nodes. Knowledge about the computed tomography (CT) characteristics of T. marneffei lymphadenopathy in HIV patients is limited. The aim of this study was to investigate the clinical and CT characteristics of T. marneffei lymphadenopathy to improve its diagnosis and promote recognition of this type of infection in radiology. Methods: Between February 2019 and June 2021, we retrospectively reviewed the clinical features and CT characteristics of T. marneffei lymphadenopathy in 21 HIV patients. Results: The clinical symptoms of T. marneffei infection are non-specific. Anemia (100%), fever (85.7%) and cough and sputum production (76.2%) were the most frequent symptoms. Multiple lymphadenopathies, mainly in the mediastinum (76.2%) and mesentery (82.4%), can be fused (14.3%) and necrotic (52.4%), with slight (41.7%) and moderate enhancement (58.3%) that is heterogeneous. In addition to involving the lymph nodes, the lesions involved the lungs (81.0%), liver and spleen (42.9%), and small intestine (14.3%). Conclusions: T. marneffei is prone to affecting lymph nodes and extranodal organs in HIV patients. Although the clinical manifestations of T. marneffei infection are not specific, the possibility of T. marneffei infection should be considered if CT findings indicate multiple lesion sites.

Xin-Ji-Er-Kang protects heart from ischemia-reperfusion injury by rebalancing lipid metabolism.

Background and Purpose: We have previously reported a cardioprotective effect with Xin-Ji-Er-Kang (XJEK) treatment in mice with myocardial infarction (MI)-induced heart failure, but no report about its potential functions in myocardial ischemia-reperfusion (MIR) injury. Here we studied the therapeutic effects of XJEK on MIR injury and investigated the mechanisms involved. Experimental Approach: MIR model of Balb/c mice induced by left anterior descending coronary artery ligation for half an hour, followed by reperfusion, was utilized to study the potential therapeutic effects of XJEK on MIR-induced cardiac injury. Ultra-performance liquid chromatography tandem Orbitrap mass spectrometry platform was used for studying serum lipid metabolic signatures. Key Results: MIR caused cardiac dysfunctions, cardiac injury, myocardial fibrosis, and increased inflammation, and all the observed abnormalities caused by MIR were largely corrected by XJEK treatment. Mechanistically, XJEK exerts its cardioprotective effect in the context of MIR injury by suppressing MIR-induced inflammation and dysregulation of serum lipid metabolism. Conclusion and Implications: We have demonstrated for the first time that XJEK protects heart from MIR injury by restoring dysregulated lipidomics. Our data provide new evidence to support a therapeutic effect for XIEK on MIR-induced cardiac injury, and pave the way for exploring the therapeutic potential of XJEK in large animal study and early clinical trial.

Impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation.

Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with an anti-inflammatory propensity, on cigarette smoke (CS)-induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg·kg-1 ), while pentoxifylline (PTX) (10 mg·kg-1 ) and theophylline (THEO) (10 mg·kg-1 ) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg·kg-1 , i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30-week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF, and THEO administration led to the partial restoration of HDAC-2 activity, which was favorably associated with the reduction of ROS expression. However, combining TRI to any of these PDEIs did not synergistically augment HDAC-2 activity. Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.

tRNA-derived fragments tRFGlnCTG induced by arterial injury promote vascular smooth muscle cell proliferation.

tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) are originated from the specific cleavage of endogenous tRNAs or their precursors and regulate gene expression when the cells are in stressful circumstances. Here, we replicated the rat common carotid artery (CCA) intimal hyperplasia model and investigated the expression of tRFs/tiRNAs in the artery. The normal and the balloon-injured rat CCAs were subjected to small RNA sequencing, and then the differentially expressed tRFs/tiRNAs were identified and analyzed. The expression profiles of tRFs/tiRNAs in the healthy and injured CCAs were remarkably different. tRNAGlnCTG-derived fragments (tRFGlnCTG) were found to be overexpressed with a high abundance in the injured CCA. In in vitro experiments, the synthetic tRFGlnCTG mimetics elevated the proliferation and migration of rat vascular smooth muscle cells (VSMCs). Through bioinformatics analysis and an overexpression experiment, tRFGlnCTG was found to negatively regulate the expression of FAS cell surface death receptor (FAS). This study revealed that tRFGlnCTG is a crucial regulator in promoting VSMC proliferation. The investigation of the roles of tRFs/tiRNAs is of significance for understanding the mechanism, diagnosis, and treatment of intimal hyperplasia.

An Optimized Enhanced Recovery After Surgery (ERAS) Pathway Improved Patient Care in Adolescent Idiopathic Scoliosis Surgery: A Retrospective Cohort Study.

OBJECTIVE: An optimized Enhanced Recovery After Surgery (ERAS) program is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in patients with surgically treated AIS. METHODS: In total, 79 patients with AIS who underwent corrective surgery without 3-column osteotomy were recruited from Xijing Hospital of the Fourth Military Medical University between 2012 and 2018. Forty-four patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin level, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay, and postoperative complications. RESULTS: There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation, and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than in the traditional group. CONCLUSIONS: The ERAS pathway is capable of improving the perioperative status of patients with AIS by offering stronger analgesia, faster ambulation, and earlier discharge.

Whether glycine betaine improves the thermotolerance of mesophilic anammox consortia.

While the application of mesophilic anammox process is currently the state of the art, the feasibility of a thermophilic anammox bioprocess is still unclear. In this study, we investigate whether glycine betaine (GB) addition can enhance the thermotolerance of mesophilic anammox biomass in the upflow anaerobic sludge blanket (UASB) reactors fed with synthetic wastewater at a nitrogen loading of approximately 4 kg N m-3 d-1. The results showed that during a long-term operation at 45°C with GB (0, 0.1, 1, 2 mM) addition, anammox performance became worse with the final effluent concentrations of NO2 -N of 145 ± 11.6 mg L-1 and nitrogen removal efficiency decreased from 92.3-6.9%. Specific anammox activity decreased from 392.1 ± 12.1-6.0 ± 0.8 mg N g-1 VSS d-1, which were not significantly higher than those in the control reactor. The content of heme c showed a stronger downward trend in T1 (with GB addition) than in the control reactor T0. The qPCR results showed that the relative abundance of Candidatus Kuenenia decreased in both the experimental (from 53.5-28.8%) and control reactors (from 54.1-35.1%). Overall, continuous addition of exogenous GB did not improve the thermotolerance of mesophilic anammox consortia at 45°C.

Associations of vitamin D with novel and traditional anthropometric indices according to age and sex: a cross-sectional study in central southern China.

PURPOSE: Vitamin D insufficiency and obesity are recognized as worldwide concerns and have been linked with each other. New anthropometric indices reflect visceral obesity better than traditional anthropometric indices. Our aim was to identify the specific correlations of novel and traditional anthropometric indices with 25-hydroxyvitamin D (25(OH)D) concentrations by sex and age. METHODS: Cross-sectional data on sociodemographic characteristics, lifestyle factors, clinical characteristics and biochemical measurements were collected for 12,617 Chinese adults. Four traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and two novel anthropometric indices, body roundness index (BRI) and body shape index (ABSI), were calculated. RESULTS: In both sexes, the mean values of BMI, WC, WHtR and BRI tended to increase with 25(OH)D insufficiency, regardless of adjustment (all P < 0.05). Males with insufficient 25(OH)D had increased odds of obesity (assessed by BMI, WC, WHtR, BRI and ABSI) compared to the odds of males with sufficient 25(OH)D. Females with insufficient 25(OH)D had a higher chance of general obesity (assessed by BMI). Low 25(OH)D status was associated with indicators of obesity only in participants aged 45-64 years in both sexes. CONCLUSION: A inverse association between obesity and lower vitamin D levels was found. Moreover, in addition to BMI, novel indicators of visceral adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations in males. The effects of optimizing vitamin D levels in obese Chinese adults need further examination, particularly in middle-aged males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Suppression of circDcbld1 Alleviates Intimal Hyperplasia in Rat Carotid Artery by Targeting miR-145-3p/Neuropilin-1.

We replicated the rat common carotid artery (CCA) intima hyperplasia model and found the expression of a circular RNA, circRNA_009723 (circDcbld1), was markedly increased in the CCA with intimal hyperplasia. In vitro, the suppression of circDcbld1 in rat vascular smooth muscle cells (VSMCs) led the increase of contractile smooth muscle cell markers and the decrease of cell migration. In vivo, the injection of chemically modified circDcbld1 small interfering RNA (siRNA) lessened the formation of neointima in rat CCA after balloon injury. Further experiments proved that circDcbld1, as a competing endogenous RNA, interacted with miR-145-3p and upregulated the level of neuropilin-1 (Nrp1), thereby regulating the migration of VSMCs. In this study, we demonstrated a new mechanism by which circular RNA promotes intimal hyperplasia. We deem that intervention in the circDcbld1-miR-145-3p/Nrp1 pathway might be a feasible approach to alleviate the post-injury intimal hyperplasia.

The protective effect of Phellinus linteus decoction on podocyte injury in the kidney of FSGS rats.

BACKGROUND: This study aimed to investigate the effect of the Phellinus linteus (Mesima) decoction on podocyte injury in a rat model of focal and segmental glomerulosclerosis (FSGS) and evaluate the potential mechanisms. METHODS: FSGS resembling primary FSGS in humans was established in rats by uninephrectomy and the repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, low-dose group of P. linteus decoction (PLD-LD), medium-dose group of P. linteus decoction (PLD-MD), and high-dose group of P. linteus decoction (PLD-HD). Blood and urine analysis were performed after 12 weeks and the molecular indicators of renal function and the renal pathological changes were examined. RESULTS: FSGS developed within 12 weeks in the test group and showed progressive proteinuria and segmental glomerular scarring. Urinary protein, serum creatinine, urea nitrogen, triglycerides and cholesterol were significantly reduced following the 12-week intervention with P.linteus decoction, especially in the PLD-LD group. Renal nephrin and podocin were markedly increased. Moreover, the pathological damage in the renal tissue was alleviated by the PLD-LD intervention. CONCLUSION: The P. linteus decoction alleviated the podocyte injury in the FSGS rat model, thus minimizing the progression of glomerular sclerosis and improving renal function.

Deciphering the microbial and genetic responses of anammox biogranules to the single and joint stress of zinc and tetracycline.

The feasibility of using anaerobic ammonium oxidation (anammox) process to treat wastewaters containing antibiotics and heavy metals was evaluated in this study. The nitrogen removal performance and characteristic parameters were monitored during the whole experimental period of 258 d. The single and joint effects of zinc and tetracycline on the microbial community were studied in upflow anaerobic sludge blanket (UASB) reactors. The anammox performance remained at levels comparable with the initial state at the lower inhibitor concentrations (zinc, 0-2.26 mg L-1; tetracycline, 0-0.5 mg L-1). When the concentrations of zinc and tetracycline increased to 3.39 mg L-1 in R1 and 1.0 mg L-1 in R2, an obvious deterioration in performance was observed. Dual inhibitors with a total concentration of ≥3 mg L-1 caused dramatic decreases in the nitrogen removal efficiency of R3. The quantification results showed that the abundances of eight antibiotic resistance genes (ARGs), czcA and intI1 in the experimental reactors generally increased under stress from metals or/and antibiotics, with final values higher than in the control, while the functional gene abundances were lower. Moreover, most genes exhibited significant correlations. Microbial community analysis indicated that Planctomycetes (represented by Candidatus Kuenenia) was inhibited by both zinc and tetracycline, but still held the dominant position. Furthermore, Caldilinea (belonging to Chloroflexi) maintained a higher abundance during the inhibitory period, implying its potential resistance to both inhibitors. These findings suggested that anammox could be inhibited by metals and antibiotics, but it has the potential to remove nitrogen from wastewaters containing both of them within the concentration threshold.

The performance and microbial community in response to MnO2 nanoparticles in anammox granular sludge.

The response of anaerobic ammonium oxidation (anammox) process and granular sludge in the upflow anaerobic sludge blanket reactor was analyzed under long-term exposure to MnO2 nanoparticles (NPs) (1-200 mg L-1). The addition of 200 mg L-1 MnO2 NPs had a significantly positive effect on nitrogen removal and this system exhibited excellent performance, with a total nitrogen removal efficiency of 93.1%. Moreover, the specific anammox activity enhanced with increasing concentrations of MnO2 NPs up to the maximum value of 657.3 ±â€¯9.3 mg TN g-1 VSS d-1 under MnO2 NPs concentration of 200 mg L-1. This value was approximately 1.6-fold higher than that of the reactor in the absence of MnO2 NPs. The extracellular polymeric substances and settling velocity were both increased with MnO2 NPs addition. Meanwhile, the high-throughput sequencing results revealed that MnO2 NPs increased the relative abundance of dominant bacteria (Candidatus Kuenenia) from 17.3% at the absence of MnO2 NPs to 23.9% at 200 mg L-1 MnO2 NPs, which resulted in a higher efficiency of biological nitrogen removal on the anammox system. These results indicated that MnO2 NPs enhanced nitrogen removal performance of anammox process.

Inhibiting a spinal cord signaling pathway protects against ischemia injury in rats.

OBJECTIVE: The aim of the study was to examine whether the cannabinoid agonist WIN55212-2 could attenuate ischemic spinal cord injury (SCI) in rats through inhibition of GAPDH/Siah1 signaling. METHODS: Male Sprague-Dawley rats were distributed randomly into 5 groups: (1) sham group that received no aortic occlusion and injected intraperitoneally (i.p.) with vehicle control after reperfusion; (2) control group that received a 12-minute aortic occlusion and injected i.p. with vehicle control after reperfusion; (3) WIN55212-2 group (WIN) that received the aortic occlusion and injected i.p. with 1 mg/kg of WIN55212-2 after reperfusion; and (4) WIN55212-2 plus AM251 group and (5) WIN55212-2 plus AM630 group that received the same surgical operation as the WIN group, except that 1 mg/kg of AM251 or AM630 was injected i.p. 30 min before each dose of WIN55212-2 injection, respectively. Neurologic function was assessed 48 hours after reperfusion. Histopathologic examination was performed to determine the number of normal neurons in anterior spinal cord. Protein expression of active caspase-3, total caspase-3, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), inducible nitric oxide synthase (iNOS), nuclear factor kappa light chain enhancer of activated B cells (NF-κB), Siah1, tumor necrosis factor α, and interleukin 1ß were determined with Western blot and enzyme-linked immunosorbent assay; coimmunoprecipitation assays were also used to determine GAPDH/Siah1 complexing. Finally, terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to determine neuronal apoptosis in the lumbar spinal cord. RESULTS: The nuclear translocation of GAPDH and Siah1 in the spinal cord was initiated after ischemic spinal cord injury (SCI) along with the increased formation of GAPDH/Siah1 complexes. However, the activation of GAPDH/Siah1 was blocked by WIN. In addition, the treatment of WIN55212-2 promoted neuronal survival in the spinal cord, reduced apoptosis and inflammation, and improved neurologic scores. Furthermore, these beneficial effects of WIN55212-2 were abolished by the combined treatment of the CB2 antagonist AM630, but not the CB1 antagonist AM251. CONCLUSIONS: Our findings reveal GAPDH/Siah1 signaling cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2 with the potential to treat ischemic SCI by targeting this pathway.

Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression. METHODS: A rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8 weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF-α were examined via RT-PCR. RESULTS: The isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-α. CONCLUSIONS: BMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy.

Roles of MnO2 on performance, sludge characteristics and microbial community in anammox system.

The long-term impacts of MnO2 on performance, sludge characteristics and microbial community of biogranule-based anaerobic ammonium oxidation (anammox) process were evaluated in an up-flow anaerobic sludge blanket reactor. It was found that the total nitrogen removal efficiency of reactor was fluctuated between 90%-93% at 1-200mgL-1 MnO2. Notably, the specific anammox activity was increased to maximum value of 657.3±10.6mgTNg-1VSSd-1 at 50mgL-1 MnO2 and then slightly decreased, but still higher than that achieved at 0-15mgL-1 MnO2, which had similar variation trends to the content of heme c and extracellular polymeric substances in anammox granules. High throughput sequencing indicated that MnO2 could improve the microbial richness and diversity of anammox granules and Candidatus Kuenenia was always the dominant species, and its abundance continued to increase to 21.3% at the end of operational experiment. Therefore, MnO2 could be applied to enhance the anammox process and the optimal influent MnO2 concentration was lower than 50mgL-1 in view of the reactor performance and cost issues.

Electroacupuncture pretreatment attenuates spinal cord ischemia-reperfusion injury via inhibition of high-mobility group box 1 production in a LXA4 receptor-dependent manner.

Paraplegia caused by spinal cord ischemia is a severe complication following surgeries in the thoracic aneurysm. HMGB1 has been recognized as a key mediator in spinal inflammatory response after spinal cord injury. Electroacupuncture (EA) pretreatment could provide neuroprotection against cerebral ischemic injury through inhibition of HMGB1 release. Therefore, the present study aims to test the hypothesis that EA pretreatment protects against spinal cord ischemia-reperfusion (I/R) injury via inhibition of HMGB1 release. Animals were pre-treated with EA stimulations 30min daily for 4 successive days, followed by 20-min spinal cord ischemia induced by using a balloon catheter placed into the aorta. We found that spinal I/R significantly increased mRNA and cytosolic protein levels of HMGB1 after reperfusion in the spinal cord. The EA-pretreated animals displayed better motor performance after reperfusion along with the decrease of apoptosis, HMGB1, TNF-α and IL-1ß expressions in the spinal cord, whereas these effects by EA pretreatment was reversed by rHMGB1 administration. Furthermore, EA pretreatment attenuated the down-regulation of LXA4 receptor (ALX) expression induced by I/R injury, while the decrease of HMGB1 release in EA-pretreated rats was reversed by the combined BOC-2 (an inhibitor of LXA4 receptor) treatment. In conclusion, EA pretreatment may promote spinal I/R injury through the inhibition of HMGB1 release in a LXA4 receptor-dependent manner. Our data may represent a new therapeutic technique for treating spinal cord ischemia-reperfusion injury.

GAPDH/Siah1 cascade is involved in traumatic spinal cord injury and could be attenuated by sivelestat sodium.

The glyceraldehyde-3-phosphate dehydrogenase (GAPDH)/Siah1 signaling pathway has been recognized as a sensor of nitric oxide (NO). It is associated with a variety of injurious conditions, suggesting its therapeutic potential for spinal cord injury (SCI). Sivelestat sodium (SIV), a neutrophil elastase (NE) inhibitor initially used to treat acute lung injury, has been known to protect against compression-induced and ischemic SCI. However, little is known about the relationship between the GAPDH/Siah1 cascade and SIV. Thus, we aimed to assess the role of GAPDH/Siah1 cascade in traumatic SCI and its possible link with SIV. Rats were assigned to four groups: sham group, SCI group, 5-mg/kg SIV group, and 10-mg/kg SIV. The traumatic SCI was induced by dropping a 10-g impactor from a height of 25mm on the dorsal surface of T9 and T10. SIV was injected intraperitoneally immediately after surgery. Our results showed that the nuclear translocation of GAPDH was induced together with the nuclear translocation of Siah1 and the formation of the GAPDH/Siah1 complex in the spinal cord after traumatic SCI. However, the activation of the GAPDH/Siah1 cascade was attenuated by treatment with SIV. We also found that SIV suppressed apoptosis, NE and inducible nitric oxide synthase (iNOS) protein expressions, the number of NE and iNOS immunostained cells, the production of interleukin (IL)-1ß and tumor necrosis factor-alpha (TNF-α), and the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) signaling in the spinal cord. The behavioral tests showed that SIV promoted functional recovery after traumatic SCI as reflected in the sustained increase in the Basso-Beattie-Bresnahan (BBB) scores throughout the observation period. In conclusion, our results reveal GAPDH/Siah1 as a novel signaling pathway during the progression of SCI, which can be blocked by SIV.