The relationship between living alone or not and depressive symptoms in older adults: a parallel mediation effect of sleep quality and anxiety.

BACKGROUND: With modernization and ageing in China, the population of older adults living alone is increasing. Living alone may be a potential risk factor for depressive symptoms. However, no parallel mediation model analysis has investigated the mediating factors for living alone or not (living arrangements) and depressive symptoms. METHODS: This cross-sectional study included a total number of 10,980 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), 1699 of whom lived alone and 9281 of whom did not live alone. Binary logistic regression and parallel mediation effect model were used to explore the relationship between living alone or not and depressive symptoms and possible mediation effects. Bootstrap analysis was used to examine the mediation effect of living alone or not on depressive symptoms. RESULTS: Compared to the participants who were not living alone, the living alone group had a higher rate of depressive symptoms. The binary logistic regression showed that after adjusting for other covariates, the risk of depressive symptoms was approximately 0.21 times higher for living alone compared to not living alone (OR = 1.21, 95% CI: 1.06, 1.37). Further, the results of the bootstrap analysis supported the partial mediating role of sleep quality and anxiety. Mediation analysis revealed that sleep quality and anxiety partially mediate the relationship between living alone and depressive symptoms (ß = 0.008, 95% CI [0.003, 0.014]; ß = 0.015, 95% CI [0.008, 0.024], respectively). CONCLUSIONS: Sleep quality and anxiety were identified as partially parallel mediators between living alone or not and depressive symptoms. Older adults living alone with poorer sleep quality and more pronounced anxiety were positively associated with higher levels of depressive symptoms. Older adults living alone should be encouraged to engage in social activities that may improve sleep quality, relieve anxiety, and improve feelings of loneliness caused by living alone. Meanwhile, older adults living alone should receive attention and support to alleviate their depressive symptoms.

Metabolomics Study of Whole-body Vibration on Lipid Metabolism of Skeletal Muscle in Aging Mice.

Ageing increases the occurrence and development of many diseases. Exercise is believed to be an effective way to improve ageing and skeletal muscle atrophy. However, many elderly people are unable to engage in active exercise. Whole-body vibration is a passive way of moving that is especially suitable for the elderly and people who find it inconvenient to exercise. Metabolomics is the systematic study of metabolic changes in small molecules. In this study, metabolomics studies were performed to investigate the regulatory effect of whole-body vibration on the skeletal muscles of ageing mice. After 12 weeks, we found that whole-body vibration had the most obvious effect on lipid metabolism pathways (such as linoleic acid, α-linolenic acid metabolism, glycerophospholipid metabolism pathways) in skeletal muscle of ageing mice. Through further research we found that whole-body vibration decreased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein in blood; decreased the lipid deposition in skeletal muscle; decreased the protein expression of monocyte chemoattractant protein-1 and interleukin-6; improved the protein levels of phosphorylated insulin receptor substrate-1, phosphate phosphoinositide 3-kinase and p-AKT; improved the protein levels of klotho; and decreased the protein expression of p53. These findings reveal that whole-body vibration might postpone senility by attenuating lipid deposition and reducing chronic inflammation and the insulin resistance of skeletal muscle.

Receptor for Advanced Glycation End-Products (RAGE) Blockade Do Damage to Neuronal Survival via Disrupting Wnt/ß-Catenin Signaling in Spinal Cord Injury.

Wnt signaling are recognized key factors in neuronal development, cell proliferation and axonal guidance. However, RAGE effect on wnt signaling after spinal cord injury (SCI) are poorly understood. Our study aims to explore RAGE blockade effect on wnt signaling after SCI. We constructed Allen SCI model and micro-injected with RAGE neutralizing antibody or IgG after injury. We determined ß-catenin, wnt3a and its receptor frizzled-5 via Western blot. We determined ß-catenin/NeuN expression at 2 weeks after SCI via immunofluorescence (IF). We found that ß-catenin, wnt3a and wnt receptor frizzled5 expression were activated after SCI at 3 days after injury. However, RAGE blockade inhibit ß-catenin, wnt3a and frizzled5 expression. We found that ß-catenin accumulation in NeuN cells were activated after SCI via IF, however, RAGE blockade reduced ß-catenin and NeuN positive cells. RAGE blockade attenuated number of survived neurons and decreased area of spared white matter around the epicenter. RAGE signaling may involved in disrupting wnt signaling to aids neuronal recovery after SCI.

MiR-429 improved the hypoxia tolerance of human amniotic cells by targeting HIF-1α.

MicroRNA-429(miR-429) plays an important role in mesenchymal stem cells. Hypoxia-inducible factor 1α (HIF-1α) is a nuclear transcription factor that regulates the proliferation, apoptosis and tolerance to hypoxia of mesenchymal stem cells. HIF-1α is also a target gene of miR-429. We investigated whether miR-429 plays a role in hypoxia tolerance with HIF-1α in human amniotic mesenchymal stem cells (hAMSCs). The expression of miR-429 was increased by hypoxia in hAMSCs. miR-429 expression resulted in decreased HIF-1α protein level, but little effect on HIF-1α mRNA. While overexpression of HIF-1α increased the survival rate and exhibited anti-apoptosis effects in hAMSCs under hypoxia, co-expression of miR-429 reduced survival and increased apoptosis. However, miR-429 silencing with HIF-1α overexpression stimulated cell survival and reduced apoptosis. Co-expression of HIF-1α and miR-429 reduced VEGF and Bcl-2 proteins and increased Bax and C-Caspase-3 levels in hAMSCs under hypoxia compared with cells expressing only HIF-1α; cells with HIF-1α overexpression and miR-429 silencing showed the opposite effects. These results indicate that HIF-1α and angomiR-429 reciprocally antagonized each other, while HIF-1α and antagomiR-429 interacted with each other to regulate survival and apoptosis in hAMSCs under hypoxia. miR-429 increased VEGF and Bcl-2 protein levels and decreased Bax and cleaved Caspase-3 protein levels by promoting the synthesis of HIF-1α. These results indicate that miR-429 negatively regulates the survival and anti-apoptosis ability of hAMSCs by mediating HIF-1α expression and improves the ability of hAMSCs to tolerate hypoxia.

Development and validation of a risk prediction model for arthritis in community-dwelling middle-aged and older adults in China.

Background: Considering its high prevalence, estimating the risk of arthritis in middle-aged and older Chinese adults is of particular interest. This study was conducted to develop a risk prediction model for arthritis in community-dwelling middle-aged and older adults in China. Methods: Our study included a total of 9599 participants utilising data from the China Health and Retirement Longitudinal Study (CHARLS). Participants were randomly assigned to training and validation groups at a 7:3 ratio. Univariate and multivariate binary logistic regression analyses were used to identify the potential predictors of arthritis. Based on the results of the multivariate binary logistic regression, a nomogram was constructed, and its predictive performance was evaluated using the receiver operating characteristic (ROC) curve. The accuracy and discrimination ability were assessed using calibration curve analysis, while decision curve analysis (DCA) was performed to evaluate the net clinical benefit rate. Results: A total of 9599 participants were included in the study, of which 6716 and 2883 were assigned to the training and validation groups, respectively. A nomogram was constructed to include age, hypertension, heart diseases, gender, sleep time, body mass index (BMI), residence address, the parts of joint pain, and trouble with body pains. The results of the ROC curve suggested that the prediction model had a moderate discrimination ability (AUC >0.7). The calibration curve of the prediction model demonstrated a good predictive accuracy. The DCA curves revealed a favourable net benefit for the prediction model. Conclusions: The predictive model demonstrated good discrimination, calibration, and clinical validity, and can help community physicians and clinicians to preliminarily assess the risk of arthritis in middle-aged and older community-dwelling adults.

Validation of the Chinese version of the Smartphone Distraction Scale.

The Smartphone Distraction Scale (SDS) is a novel assessment scale for smartphone distraction; it comprises 16 items that cover attention impulsiveness, online vigilance, multitasking, and emotion regulation. This study aimed to investigate the validity and reliability of the SDS in college students in China. After translating and culturally adapting the original version of the SDS into Chinese, the scale was tested on a sample of 1302 college students.The validity and reliability were assessed utilizing SPSS 25.0, AMOS 25.0 and Mplus 8.3. Parallel analysis, Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were performed for the validity analysis. Criterion-related validity for the SDS was tested by correlation analysis with the mobile phone addiction scale (MPAI). The reliability analysis was tested by Cronbach's alpha coefficients and intraclass correlation coefficients (ICC). EFA and parallel analysis revealed a three-factor structure. The EFA identified factor loadings on three factors (14 items), explaining a total variance of 60.73 %. The CFA model fit was good (χ2/df = 4.644, RMSEA = 0.047, GFI = 0.930, CFI = 0.955, SRMR = 0.047), and the multigroup confirmatory factor analysis indicated measurement invariance for gender. Both convergent and discriminant validity were established. The criterion-related validity was established based on a significant correlation (r = 0.758) with the MPAI. The Cronbach's alpha coefficient was 0.916, and the split-half reliability was 0.769, demonstrating a satisfactory internal consistency. The score of ICC was 0.907, demonstrating the stability of the SDS. Based on these data, the Chinese version of the SDS demonstrated satisfactory validity and reliability in a sample of college students.

Direct Melt-Calendaring of Highly Textured (Bi,Sb)2Te3 Thick Films: Superior Thermoelectric and Mechanical Performance via Strain Engineering.

The evolutions of chip thermal management and micro energy harvesting put forward urgent need for micro thermoelectric devices. Nevertheless, low-performance thermoelectric thick films as well as the complicated precision cutting process for hundred-micron thermoelectric legs still remain the bottleneck hindering the advancement of micro thermoelectric devices. In this work, an innovative direct melt-calendaring manufacturing technology is first proposed with specially designed and assembled equipment, that enables direct, rapid, and cost-effective continuous manufacturing of Bi2Te3-based films with thickness of hundred microns. Based on the strain engineering with external glass coating confinement and controlled calendaring deformation degree, enhanced thermoelectric performance has been achieved for (Bi,Sb)2Te3 thick films with highly textured nanocrystals, which can promote carrier mobility over 182.6 cm2 V-1 s-1 and bring out a record-high zT value of 0.96 and 1.16 for n-type and p-type (Bi,Sb)2Te3 thick films, respectively. The nanoscale interfaces also further improve the mechanical strength with excellent elastic modules (over 42.0 GPa) and hardness (over 1.7 GPa), even superior to the commercial zone-melting ingots and comparable to the hot-extrusion (Bi,Sb)2Te3 alloys. This new fabrication strategy is versatile to a wide range of inorganic thermoelectric thick films, which lays a solid foundation for the development of micro thermoelectric devices.

Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway.

Spinal cord injury (SCI) is an extreme neurological impairment with few effective drug treatments. Pyroptosis is a recently found and proven type of programmed cell death that is characterized by a reliance on inflammatory caspases and the release of a large number of proinflammatory chemicals. Pyroptosis differs from other cell death mechanisms such as apoptosis and necrosis in terms of morphological traits, incidence, and regulatory mechanism. Pyroptosis is widely involved in the occurrence and development of SCI. In-depth research on pyroptosis will help researchers better understand its involvement in the onset, progression, and prognosis of SCI, as well as provide new therapeutic prevention and treatment options. Herein, we investigated the role of AMPK-mediated activation of the NLRP3 inflammasome in the neuroprotection of MET-regulated pyroptosis. We found that MET treatment reduced NLRP3 inflammasome activation by activating phosphorylated AMPK and reduced proinflammatory cytokine (IL-1ß, IL-6, and TNF-α) release. At the same time, MET improved motor function recovery in rats after SCI by reducing motor neuron loss in the anterior horn of the spinal cord. Taken together, our study confirmed that MET inhibits neuronal pyroptosis after SCI via the AMPK/NLRP3 signaling pathway, which is mostly dependent on the AMPK pathway increase, hence decreasing NLRP3 inflammasome activation.

Rapid Selective Ablation and High-Precision Patterning for Micro-Thermoelectric Devices Using Femtosecond Laser Directing Writing.

Highly integrated miniature thermoelectric (TE) devices are desirable for applications of chip thermal management and self-powered energy harvesting. Currently, further performance improvement of micro-TE devices is largely limited by micro-nano-patterned processing, which shows the incompatibility with high-performance TE material fabrication or contradiction between machining accuracy and efficiency. This work presents a useful method to flexibly achieve high-precision array patterning for the micro-TE device through the femtosecond laser direct writing technique. By experimentally examining the material ablation process and numerically analyzing the electron-lattice temperature, the laser energy threshold for different materials is determined to obtain the selective removal between TE materials and metallic electrodes. Furthermore, the evaluation criteria are established between the formation quality of microgroove in the array structure and the laser pulse energy distribution, and the shape-control and property-control pattern processing can be realized through the reasonable control of the laser energy. Consequently, the Bi2Te3-based TE pattern with a competitive leg density (496 pairs/cm2) and a high filling factor (55%) is successfully constructed.

Electrical Tree Characteristics of Bisphenol A Epoxy Resin/Maleopimaric Anhydride Curing System.

Epoxy resin insulation materials are mainly derived from petrochemical materials which have the disadvantages of resource consumption and environmental pollution. In order to cure bisphenol A epoxy resin, a maleopimaric anhydride (MPA) curing agent was prepared from rosin, a renewable resource, and blended with a petroleum-based curing agent (methylhexahy-drophthalic anhydride). The influence of maleopimaric anhydride content on the initiation and growth characteristics of electrical trees was studied and analyzed in this paper using molecular dynamics simulation (MD) and electrical tree tests at an 18-kilovolt power frequency voltage. When the MPA content used was ≤10%, the free volume percentage of the curing system increased with MPA content, and thus the initiation voltage became lower; when the MPA content was ≥20%, the hydrogenated phenanthrene ring structure content increased significantly with increasing MPA content, and the rigidity of the curing system increased significantly; thus, the initiation voltage gradually increased. MPA4 had an 11.11% higher initiation voltage than the petroleum-based control group. The effect of the polar rigid structure within the curing system significantly inhibited the growth rate and length of electrical trees as MPA content increased. Electrical trees developed into light-colored, thin, and narrow dendritic structures when the MPA content reached 40%. The results show that curing epoxy resin with the rosin-based curing agent maleopimaric anhydride (MPA), in place of a petroleum-based curing agent, can produce environmentally friendly resins with excellent electrical tree resistance and potential application prospects.

Nischarin downregulation attenuates cell injury induced by oxidative stress via Wnt signaling.

Nischarin (NISCH) is a key protein functioning as a molecular scaffold and thereby hosting interactions with several protein partners. Here, we aimed to investigate whether NISCH downregulation could protect rat pheochromocytoma (PC12) cells against oxidative stress-induced injury using a model of cell injury induced by hydrogen peroxide (H2O2). Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis rate was evaluated using flow cytometry. The expressions of apoptosis-related proteins Bax, Bcl-2, caspase-3 and NISCH were examined via Western blot analysis and immunofluorescence staining analyses. The expressions of NISCH, glycogen synthase kinase-3ß (GSK-3ß) and T-cell factor-1 (TCF-1) were examined using Western blot analysis. The results showed that incubation of H2O2 for 48 h significantly decreased the cell viability, increased the cell apoptosis rate and the NISCH expression in PC12 cells, whereas NISCH downregulation blocked the effects of H2O2 on cells. In addition, the expression of Bcl-2 was significantly reduced, and the expression of Bax and caspase-3 were significantly increased by H2O2 treatment. However, these effects were partially inhibited by the downregulation of NISCH. Furthermore, H2O2 significantly weakened the transduction of Wnt signaling, including the increases of GSK-3ß and TCF-1 expressions and the decrease of ß-catenin expression, while NISCH downregulation attenuated the effect of H2O2 on Wnt signaling. Moreover, inhibition of the Wnt pathway further decreased the cell viability and promoted the cell apoptosis induced by H2O2 in PC12 cells. Our results suggest that NISCH downregulation may protect cells against oxidative stress-induced injury through regulating the transduction of Wnt signaling.

Outcome of Humeral Shaft Fracture Treated with Intramedullary Nail and Plate Fixation.

OBJECTIVE: To compare the results of the intramedullary nail (IMN) and compression plate fixation performed for humeral shaft fracture as to determine a better option out of the two. STUDY DESIGN: Comparative study. PLACE AND DURATION OF STUDY: First Affiliated Hospital of Jinzhou Medical University, Liaoning, PR China, from October 2016 to January 2019. METHODOLOGY: Patients treated with IMN (n=26) or plate fixation (n=30) for humeral shaft fracture were included in this study. Assessment was done in terms of perioperative parameters, complications, union time, and functional outcomes. Functional outcome were compared between the two groups at each follow-up (6 weeks, 3, 6, and 12 months) and between the subsequent follow-ups in both groups using the repeated measures ANOVA. RESULTS: Intraoperative blood loss, operative time, hospital stay, and union time were significantly lower in the IMN group. There was no significant difference in the functional outcomes when it was compared between the two groups at each follow-up. However, when it was compared between subsequent follow-ups, a significant improvement was observed in both groups. Increase incidence of individual complication and reoperation were established in the plating group, but without a significant difference. Yet, the overall complications rate was significantly higher in the plating group. CONCLUSION: IMN fixation led to a significant decrease in intraoperative blood loss, shorter operating time, hospital stay, union time, and a lower rate of overall complications. Thus, IMN may be a better choice of internal fixation as it also accelerates the patients' recovery, and increases their satisfaction.

miR-193-3p ameliorates bone resorption in ovariectomized mice by blocking NFATc1 signaling.

BACKGROUND: Nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) as a key transcription factor contributes to osteoclast differentiation and bone resorption. However, the post-transcriptional mechanisms of microRNAs (miRNAs) targeted to NFATc1 have not been completely clarified in postmenopausal osteoporosis (PMO). In our study, we aimed to investigate the role of miR-193-3p in ovariectomy (OVX)-induced bone loss by regulating the NFATc1 pathway. METHODS: Female C57BL/6J mice underwent sham or OVX operation. Injection of Agomir-Control or Agomir-miR-193-3p was performed in OVX mice. Serum, urine and tibia were collected for experimental measurements, including biochemical markers, RT-qPCR and western blotting assays. RESULTS: We identified NFATc1 as a direct target of miR-193-3p. Up-regulation of NFATc1 and down-regulation of miR-193-3p were found in the tibia of OVX mice. Gain-of-function of miR-193-3p resulted in the reduction of NFATc1 mRNA and protein expression in vivo and in vitro. Furthermore, injection of Agomir-miR-193-3p markedly ameliorated OVX-induced Ca2+ dyshomeostasis and bone loss by inhibiting the expression of NFATc1 and its downstream targets of osteoclast-specific genes, Ctsk, TRAP and Car2. CONCLUSION: Overexpression of miR-193-3p had an osteoprotective effect in OVX mice by suppressing NFATc1 pathways.

Nischarin attenuates apoptosis induced by oxidative stress in PC12 cells.

Nischarin (NISCH) is a cytoplasmic protein known to serve an inhibitory role in breast cancer cell apoptosis, migration and invasion. Recently, NISCH has been reported to be involved in the regulation of spinal cord injury (SCI). However, the molecular mechanism is still unclear. Oxidative stress contributes to tissue injury and cell apoptosis during the development of various diseases, including SCI. The aim of the present study was to investigate the role of NISCH in the regulation of apoptosis induced by oxidative stress in PC12 cells. H2O2 was used to establish an oxidative stress model in PC12 cells. Apoptosis levels were examined using flow cytometry analysis, and the expression of NISCH, Bcl-2, Bcl-2-associated X (Bax) and caspase-3 were examined using western blot and immunofluorescence staining analyses. The results demonstrated that treatment with 100 µM H2O2 significantly increased the apoptotic rate and expression of NISCH in PC12 cells. At 48 h following incubation with 100 µM H2O2, NISCH downregulation partially inhibited apoptosis of PC12 cells. In addition, the expression of Bcl-2 was significantly reduced and the expression of Bax and caspase-3 were significantly increased by H2O2 treatment. These effects were also partially inhibited by the downregulation of NISCH. The authors of the present study therefore hypothesize that NISCH may function as a pro-apoptotic protein that participates in the regulation of oxidative stress, and NISCH downregulation may protect cells from oxidative stress-induced apoptosis.

Blockade of receptor for advanced glycation end products promotes oligodendrocyte autophagy in spinal cord injury.

Receptor for advanced glycation end product (RAGE) is involved in neuronal inflammation, cell cycle and differentiation. However, the role of RAGE in autophagy in the process of spinal cord injury (SCI) is yet unknown. The present study investigated the effect of RAGE blockade on autophagy in SCI. A rat Allen SCI model was established and the animals were micro-injected with rabbit RAGE neutralizing antibody or rabbit polyclonal Ig G immediately after the injury. The oligodendrocytes(OLs) marker, 2', 3'-cyclic nucleotide 3'-phosphodiesterase(CNPase) and autophagy-related marker microtubule associated protein light chain 3B(LC3B) were evaluated by Western blot. Furthermore, myelin basic protein (MBP) and LC3B double staining were observed in the SCI via immunofluorescence. The results showed that RAGE blockade reduced the expression of CNPase, promoted LC3B-II/I and p62 expression after SCI. In addition, the MBP/LC3B double positive oligodendrocytes-expressing LC3B was up-regulated by RAGE blockade. Moreover, RAGE blockade attenuated the neuronal survival at ventral horn after SCI. The present study revealed the role of RAGE in maintaining oligodendrocyte autophagy to promote neuronal regeneration post-SCI.

The Neuroprotective Effects of Muscle-Derived Stem Cells via Brain-Derived Neurotrophic Factor in Spinal Cord Injury Model.

Muscle-derived stem cells (MDSCs) possess multipotent differentiation and self-renewal capacities; however, the effects and mechanism in neuron injury remain unclear. The aim of this study was to investigate the effects of MDSCs on neuron secondary injury, oxidative stress-induced apoptosis. An in vivo study showed the Basso, Beattie, and Bresnahan (BBB) score and number of neurons significantly increased after MDSCs' transplantation in spinal cord injury (SCI) rats. An in vitro study demonstrated that MDSCs attenuated neuron apoptosis, and the expression of antioxidants was upregulated as well as the ratio of Bcl-2 and Bax in the MNT (MDSCs cocultured with injured neurons) group compared with the NT (injured neurons) group. Both LC3II/LC3I and ß-catenin were enhanced in the MNT group, while XAV939 (a ß-catenin inhibitor) decreased the expression of nuclear erythroid-related factor 2 (Nrf2) and LC3II/LC3I. Moreover, MDSCs became NSE- (neuron-specific enolase-) positive neuron-like cells with brain-derived neurotrophic factor (BDNF) treatment. The correlation analysis indicated that there was a significant relation between the level of BDNF and neuron injury. These findings suggest that MDSCs may protect the spinal cord from injury by inhibiting apoptosis and replacing injured neurons, and the increased BDNF and ß-catenin could contribute to MDSCs' effects.

HMGB1/Advanced Glycation End Products (RAGE) does not aggravate inflammation but promote endogenous neural stem cells differentiation in spinal cord injury.

Receptor for advanced glycation end products (RAGE) signaling is involved in a series of cell functions after spinal cord injury (SCI). Our study aimed to elucidate the effects of RAGE signaling on the neuronal recovery after SCI. In vivo, rats were subjected to SCI with or without anti-RAGE antibodies micro-injected into the lesion epicenter. We detected Nestin/RAGE, SOX-2/RAGE and Nestin/MAP-2 after SCI by Western blot or immunofluorescence (IF). We found that neural stem cells (NSCs) co-expressed with RAGE were significantly activated after SCI, while stem cell markers Nestin and SOX-2 were reduced by RAGE blockade. We found that RAGE inhibition reduced nestin-positive NSCs expressing MAP-2, a mature neuron marker. RAGE blockade does not improve neurobehavior Basso, Beattie and Bresnahan (BBB) scores; however, it damaged survival of ventral neurons via Nissl staining. Through in vitro study, we found that recombinant HMGB1 administration does not lead to increased cytokines of TNF-α and IL-1ß, while anti-RAGE treatment reduced cytokines of TNF-α and IL-1ß induced by LPS via ELISA. Meanwhile, HMGB1 increased MAP-2 expression, which was blocked after anti-RAGE treatment. Hence, HMGB1/RAGE does not exacerbate neuronal inflammation but plays a role in promoting NSCs differentiating into mature neurons in the pathological process of SCI.

Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury.

Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K. In addition, the expression of Beclin-1 and the ratio of the light-chain 3B-II (LC3B-II)/LC3B-I in the injured spinal cord significantly increased in Netrin-1 group than those in SCI group. Moreover, the ratio of apoptotic neurons in the anterior horn of the spinal cord and the cavity area of spinal cord significantly decreased in Netrin-1 group compared with those in SCI group. In addition, Netrin-1 not only preserved motor neurons but also significantly improved motor fuction of injured rats. These results suggest that Netrin-1 improved functional recovery through autophagy stimulation by activating the AMPK/mTOR signaling pathway in rats with SCI. Thus, Netrin-1 treatment could be a novel therapeutic strategy for SCI.

Berberine attenuated pro-inflammatory factors and protect against neuronal damage via triggering oligodendrocyte autophagy in spinal cord injury.

Berberine exerts neuroprotective effect in neuroinflammation and neurodegeneration disease. However, berberine effect in acute spinal cord injury is yet to be elucidated. Herein, we investigated the neuroprotective effect of berberine in spinal cord injury (SCI). Sprague-Dawley rats were subjected to SCI by an intraperitoneal injection of berberine post-injury. The neurobehavioral recovery, cytokines of pro-inflammatory factors (TNF-α and IL-1ß), autophagy-related proteins (LC3B, ATG16L, ATG7), and apoptosis-related protein cleaved caspase-3 were determined. The expressions of 2', 3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), marker of oligodendrocyte, autophagy-related proteins ATG5 and neurons at the ventral horn were assessed. In vitro, the contents of the pro-inflammatory factors, TNF-α and IL-1ß, were detected in the lipopolysaccharide (LPS)-treated primary spinal neuron. Berberine significantly improved the neurobehavior BBB score and attenuated the cytokines of pro-inflammatory factors in cerebrospinal fluid post-SCI. In addition, berberine upregulated CNPase positive oligodendrocyte expressing ATG5, promoted neuronal survival and reduced the cleaved caspase-3 expression after SCI. In primary spinal neuron, the LPS-induced inflammatory factors could be reduced by berberine, whereas the autophagy inhibitor, 3-Methyladenine reverses the effect. Berberine attenuated inflammation of the injured spinal cord and reduced the neuronal apoptosis via triggering oligodendrocyte autophagy in order to promote neuronal recovery.

Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.