Hemispherical harmonic illumination and reflectance angular spectrum.

Light scattering plays an important role in physics, with wide applications in science and engineering. However, accurate and effective modeling of scattering remains a great challenge. In this study, we exploited the rendering equation using hemispherical harmonics to demonstrate an angular frequency representation that directly depicts scattering in a two-dimensional spectrum, free from any underlying assumptions. This representation offers a compact and intuitive characterization of mirror reflection, isotropic scattering, and anisotropic emission. The robust support of theoretical proofs and data-driven experimental results establishes the broad applicability of our computational model in conducting scattering analyses across diffuse, specular, and glossy materials. With the capability to characterize the scattering in angular frequency domain, we expect our proposed model to emerge as an essential tool in various domains, including surface feature recognition, reflectance data compression, and computer rendering.

Polydatin administration attenuates the severe sublesional bone loss in mice with chronic spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is often accompanied by rapid and extensive bone mineral loss below the lesion level, and there is currently no gold standard for treatment. Evidence suggests that polydatin (PLD) may help promote osteogenic differentiation and exhibit anti-osteoporotic activity. However, whether PLD could reverse substantial bone loss in SCI patients, especially those with protracted injury, and the underlying regulatory mechanism have not been investigated. STUDY DESIGN: Male C57BL/6J mice were subjected to either contusion SCI or laminectomy at the T8-9 level. Eight weeks after SCI, PLD (40 mg/kg/day) or vehicle was administrated to the mice via the intragastric route for consecutive eight weeks. Blood was collected after the treatment regimen, and the tibiae and femora were removed. Bone marrow stromal cells were isolated from the long bones for ex vivo osteoblastogenesis and osteoclastogenesis assays. RESULTS: Chronic SCI led to a rapid and significant decrease in bone mineral density (BMD) of the distal femur and proximal tibia, resulting in structural deterioration of the bone tissues. Treatment with PLD largely restored BMD and bone structure. In addition, static histo-morphometric analysis revealed that PLD enhanced bone formation and inhibited bone resorption in vivo. PLD also promoted osteoblastogenesis and inhibited osteoclastogenesis ex vivo, which was accompanied by increased OPG/RANKL ratio, and reduced expression levels of CTR, TRAP, NFATc1 and c-Fos. However, PLD had no marked effect on serum 25(OH)D levels and VDR protein expression, although it did significantly lower serum and femoral malondialdehyde levels, inhibited expression level of matrix metallopeptidase 9 (MMP9), upregulated skeletal Wnt3a, Lrp5 and ctnnb1 mRNAs, and increased ß-catenin protein expression. CONCLUSIONS: PLD protected mice with chronic SCI against sublesional bone loss by modulating genes involved the differentiation and activity of osteoclasts and osteoblasts, abating oxidative stress and MMP activity, and restoring the Wnt/ß-catenin signaling pathway.

Bu Shen Huo Xue decoction promotes functional recovery in spinal cord injury mice by improving the microenvironment to promote axonal regeneration.

BACKGROUND: Bu-Shen-Huo-Xue (BSHX) decoction has been used in the postoperative rehabilitation of patients with spinal cord injury in China. In the present study, we aim to reveal the bioactive compounds in BSHX decoction and comprehensively explore the effects of BSHX decoction and the underlying mechanism in spinal cord injury recovery. METHODS: The main chemical constituents in BSHX decoction were determined by UPLC-MS/MS. SCI mice were induced by a pneumatic impact device at T9-T10 level of the vertebra, and treated with BSHX decoction. Basso-Beattie-Bresnahan (BBB) score, footprint analysis, hematoxylin-eosin (H&E) staining, Nissl staining and a series of immunofluorescence staining were performed to investigate the functional recovery, glial scar formation and axon regeneration after BSHX treatment. Immunofluorescent staining of bromodeoxyuridine (BrdU), neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) was performed to evaluate the effect of BSHX decoction on neural stem cells (NSCs) proliferation and differentiation. RESULTS: We found that the main compounds in BSHX decoction were Gallic acid, 3,4-Dihydroxybenzaldehyde, (+)-Catechin, Paeoniflorin, Rosmarinic acid, and Diosmetin. BSHX decoction improved the pathological findings in SCI mice through invigorating blood circulation and cleaning blood stasis in the lesion site. In addition, it reduced tissue damage and neuron loss by inhibiting astrocytes activation, and promoting the polarization of microglia towards M2 phenotype. The functional recovery test revealed that BSHX treatment improved the motor function recovery post SCI. CONCLUSIONS: Our study provided evidence that BSHX treatment could improve the microenvironment of the injured spinal cord to promote axonal regeneration and functional recovery in SCI mice.

Nonwoven-based gelatin/polycaprolactone membrane loaded with ERK inhibitor U0126 for treatment of tendon defects.

BACKGROUND: Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. METHODS: Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. RESULTS: In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFß superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. CONCLUSION: Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.

Stem Cells in Tendon Regeneration and Factors governing Tenogenesis.

Tendons are connective tissue structures of paramount importance to the human ability of locomotion. Tendinopathy and tendon rupture can be resistant to treatment and often recurs, thus resulting in a significant health problem with a relevant social impact worldwide. Unfortunately, existing treatment approaches are suboptimal. A better understanding of the basic biology of tendons may provide a better way to solve these problems and promote tendon regeneration. Stem cells, either obtained from tendons or non-tendon sources, such as bone marrow (BMSCs), adipose tissue (AMSCs), as well as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have received increasing attention toward enhancing tendon healing. There are many studies showing that stem cells can contribute to improving tendon healing. Hence, in this review, the current knowledge of BMSCs, AMSCs, TSPCs, ESCs, and iPSCs for tendon regeneration, as well as the advantages and limitations among them, has been highlighted. Moreover, the transcriptional and bioactive factors governing tendon healing processes have been discussed.

Direct Interaction of Sox10 With Cadherin-19 Mediates Early Sacral Neural Crest Cell Migration: Implications for Enteric Nervous System Development Defects.

BACKGROUND AND AIMS: The enteric nervous system, which regulates many gastrointestinal functions, is derived from neural crest cells (NCCs). Defective NCC migration during embryonic development may lead to enteric neuropathies such as Hirschsprung's disease (hindgut aganglionosis). Sox10 is known to be essential for cell migration but downstream molecular events regulating early NCC migration have not been fully elucidated. This study aimed to determine how Sox10 regulates migration of sacral NCCs toward the hindgut using Dominant megacolon mice, an animal model of Hirschsprung's disease with a Sox10 mutation. METHODS: We used the following: time-lapse live cell imaging to determine the migration defects of mutant sacral NCCs; genome-wide microarrays, site-directed mutagenesis, and whole embryo culture to identify Sox10 targets; and liquid chromatography and tandem mass spectrometry to ascertain downstream effectors of Sox10. RESULTS: Sacral NCCs exhibited retarded migration to the distal hindgut in Sox10-null embryos with simultaneous down-regulated expression of cadherin-19 (Cdh19). Sox10 was found to bind directly to the Cdh19 promoter. Cdh19 knockdown resulted in retarded sacral NCC migration in vitro and ex vivo, whereas re-expression of Cdh19 partially rescued the retarded migration of mutant sacral NCCs in vitro. Cdh19 formed cadherin-catenin complexes, which then bound to filamentous actin of the cytoskeleton during cell migration. CONCLUSIONS: Cdh19 is a direct target of Sox10 during early sacral NCC migration toward the hindgut and forms cadherin-catenin complexes which interact with the cytoskeleton in migrating cells. Elucidation of this novel molecular pathway helps to provide insights into the pathogenesis of enteric nervous system developmental defects.

Sodium tanshinone IIA sulfonate promotes spinal cord injury repair by inhibiting blood spinal cord barrier disruption in vitro and in vivo.

Spinal cord injury (SCI) leads to microvascular damage and the destruction of the blood spinal cord barrier (BSCB), which can progress into secondary injuries, such as apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. However, the therapeutic effects of STS on damaged BSCB during the early stage of SCI remain uncertain. Therefore, we exposed spinal cord microvascular endothelial cells to H2 O2 and treated them with different doses of STS. In addition to protecting the cells from H2 O2 -induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMP activation and prevented the loss of tight junction and adherens junction proteins. Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.

Effectiveness and safety of Wendan decoction for post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression (PSD) refers to a series of affective disorder syndromes that occur after stroke and are often accompanied by physical symptoms. PSD presents with low mood and lack of interest as the main characteristics along with the symptoms of stroke. The physical symptoms of PSD include sleep disorder, loss of appetite, and reluctance to communicate. Although Wendan decoction has been suggested to be effective in the treatment of PSD, there is no meta-analysis providing evidence for the usefulness of Wendan decoction for treating PSD. METHODS: The following electronic databases will be searched: the Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang databases, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. Each database will be searched from its inception to November 2021. Two independent researchers will conduct study selection, data extraction, and risk bias assessment. Any discrepancies will be resolved through consultation with a third researcher. If the included data are suitable, we will conduct a meta-analysis using RevMan v5.4 software. RESULTS: In this systematic review, the effectiveness and safety of Wendan decoction in the treatment of PSD will be evaluated. CONCLUSION: The findings of this meta-analysis will provide evidence-based data for the application of Wendan decoction in the treatment of PSD. ETHICS AND DISSEMINATION: Individual patient data and privacy will not be involved in this research,so ethics approval is not required. INPLASY REGISTRATION NUMBER: INPLASY2021110018.

Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by reducing oxidative stress, apoptosis, and inflammatory response.

BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved. METHODS: The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days. RESULTS: We found that TUDCA attenuated axon degeneration induced by H2O2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function. CONCLUSIONS: TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

Effectiveness and safety of moxibustion for Parkinson disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Parkinson disease (PD) is a common neurodegenerative disease among middle-aged and elderly people. Clinically, it is a movement disorder characterized mainly by static tremors, kinesia, myotonia, and postural balance disorder. In recent years, an increasing number of clinical reports on moxibustion therapy for PD have been published. Despite this, no systematic review of moxibustion therapy for PD has been undertaken. METHODS: Two reviewers will search the following 7 English and Chinese databases online: the Cochrane Library; PubMed; EMBASE; the China National Knowledge Infrastructure; the Wan Fang databases; the China Science and Technology Journal Database; and the Chinese Biomedical Literature Database. Reviewers will search each electronic database for studies published from journal inception to May 2021. Two reviewers will independently conduct clinical study inclusion, data extraction, and risk bias assessment. Any differences in the above process will be resolved through discussion with a third reviewer. If the data are sufficient, RevMan software 5.3 (Cochrane Community, London, UK) will be used for the meta-analysis of the extracted data. RESULTS: In this systematic review, the effectiveness and safety of moxibustion therapy in PD treatment will be evaluated. CONCLUSION: This systematic review may provide further evidence to encourage clinicians to use moxibustion in the treatment of PD. INPLASY REGISTRATION NUMBER: INPLASY202140097.

Polydatin Attenuates OGD/R-Induced Neuronal Injury and Spinal Cord Ischemia/Reperfusion Injury by Protecting Mitochondrial Function via Nrf2/ARE Signaling Pathway.

Spinal cord ischemia/reperfusion injury (SCII) is a devastating complication of spinal or thoracic surgical procedures and can lead to paraplegia or quadriplegia. Neuronal cell damage involving mitochondrial dysfunction plays an important role in the pathogenesis of SCII. Despite the availability of various treatment options, there are currently no mitochondria-targeting drugs that have proven effective against SCII. Polydatin (PD), a glucoside of resveratrol, is known to preserve mitochondrial function in central nervous system (CNS) diseases. The aim of the present study was to explore the neuro- and mito-protective functions of PD and its underlying mechanisms. An in vitro model of SCII was established by exposing spinal cord motor neurons (SMNs) to oxygen-glucose-deprivation/reperfusion (OGD/R), and the cells were treated with different dosages of PD for varying durations. PD improved neuronal viability and protected against OGD/R-induced apoptosis and mitochondrial injury in a dose-dependent manner. In addition, PD restored the activity of neuronal mitochondria in terms of mitochondrial membrane potential (MMP), intracellular calcium levels, mitochondrial permeability transition pore (mPTP) opening, generation of reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels. Mechanistically, PD downregulated Keap1 and upregulated Nrf2, NQO-1, and HO-1 in the OGD/R-treated SMNs. Likewise, PD treatment also reversed the neuronal and mitochondrial damage induced by SCII in a mouse model. Furthermore, the protective effects of PD were partially blocked by the Nrf2 inhibitor. Taken together, PD relieves mitochondrial dysfunction-induced neuronal cell damage by activating the Nrf2/ARE pathway and is a suitable therapeutic option for SCII.

De-osteogenic-differentiated mesenchymal stem cells accelerate fracture healing by mir-92b.

BACKGROUND: Mesenchymal stem cells (MSCs) are promising targets for therapeutic use in regenerative medicine and tissue engineering. In the previous study, we have found that MSCs could be reverted to a primitive stem cell population after in vitro induction of osteogenic and de-osteogenic differentiation (de-osteogenic differentiated MSCs, De-Os-MSCs). De-Os-MSCs showed improved cell survival and osteogenic potential. However, the underlying mechanism and its potential effect on fracture healing has not been explored. METHODS: MSCs were isolated from the rat bone marrow. MicroRNAs were cloned into lentiviral vectors and transduced into MSCs to observe the effects on osteogenesis. The expression levels of marker genes were evaluated by quantitative RT-PCR. Ectopic bone formation model was used to evaluate the bone regeneration ability of mir-92b transduced MSCs in vivo. An open femur fracture model was established, and MSCs or De-Os-MSCs were administrated to the fracture sites. Histological, biomechanical and microCT analysis were used to evaluate the quality of bone. RESULTS: In the present study, we found that mir-92b was significantly increased in the secretions of De-Os-MSCs. And mir-92b could promote the osteogenic differentiation potential of MSCs by activating pERK and JNK signaling pathways. The ectopic bone formation assay showed that MSCs overexpressing mir-92b formed more bone like tissues in vivo. Most importantly, we found local administration of De-Os-MSCs could accelerate fracture healing using an open femur fracture model in rats. The quality of bone property was much better as shown by microCT and biomechanical testing. CONCLUSION: Taken together, our study demonstrated that mir-92b promoted osteogenesis of MSCs, which was partially accounted for the enhanced osteogenic differentiation potential of De-Os-MSCs. And De-Os-MSCs had shown better regenerative capacity in accelerating fracture healing when they were locally given. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: De-Os-MSCs could be used to accelerate fracture healing, and reduce the occurrence of delayed unions and non-unions.

Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo.

Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 µM, 3 µM, and 10 µM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.

Acupuncture plus rehabilitation for post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression (PSD) is a common stroke complication that is characterized by hopelessness, anxiety, disordered sleep, and lowered responsiveness. Rehabilitation and acupuncture treatments are often combined to treat PSD; however, there has been no meta-analysis on their synergistic effect. Therefore, we aim to perform a systematic review and meta-analysis to estimate the effectiveness of acupuncture and rehabilitation in PSD treatment. METHODS: We will search the following electronic databases: PubMed, the Cochrane Library, EMBASE, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, China Science and Technology Journal Database, and Wan Fang databases. We will include studies published between the database initiation and May 2020. Two reviewers will separately conduct study selection, data extraction, and risk of bias assessment. Disputes will be settled by consulting a third reviewer. Review Manager Software 5.3 will be employed for this meta-analysis. RESULTS: This systematic review will assess whether acupuncture combined with rehabilitation treatment is more effective than rehabilitation alone in the management of PSD. CONCLUSION: This systematic review will provide evidence regarding the synergistic effect of acupuncture and rehabilitation treatment for PSD.

Polydatin promotes the neuronal differentiation of bone marrow mesenchymal stem cells in vitro and in vivo: Involvement of Nrf2 signalling pathway.

Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising repair strategy following spinal cord injury (SCI), although the therapeutic effects are minimal due to their limited neural differentiation potential. Polydatin (PD), a key component of the Chinese herb Polygonum cuspidatum, exerts significant neuroprotective effects in various central nervous system disorders and protects BMSCs against oxidative injury. However, the effect of PD on the neuronal differentiation of BMSCs, and the underlying mechanisms remain inadequately understood. In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 µmol/L) markedly facilitated BMSC differentiation into neuron-like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites. Furthermore, compared with either monotherapy, the combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function. Taken together, PD augments the neuronal differentiation of BMSCs via Nrf2 activation and improves functional recovery, indicating a promising new therapeutic approach against SCI.

Acupuncture plus Rehabilitation for Unilateral Neglect after Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically assess the efficacy of acupuncture combined with rehabilitation on unilateral neglect after stroke. METHODS: The Cochrane Library, PubMed, Excerpt Medical Database (EMBASE), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), and Wan Fang databases were searched online for randomised controlled trials (RCTs) of acupuncture and its effects on unilateral neglect after stroke from their inception to September 2019. RCTs on acupuncture combined with rehabilitation in the experimental group for unilateral neglect compared with rehabilitation alone or rehabilitation plus sham acupuncture in the control group were included. Two authors separately screened the literature, extracted the data, and evaluated the quality of the included studies. Review Manager 5.3 software was used for the data analysis. RESULTS: A total of 542 patients from nine RCTs were included. The meta-analysis showed that the experimental groups could significantly improve Fugl-Meyer Assessment (FMA) (MD = 11.54, 95% CI [9.54, 13.54], P < 0.00001) and the ability of daily living (SMD = 1.35, 95% CI [0.64, 2.07], P < 0.00001) and the ability of daily living (SMD = 1.35, 95% CI [0.64, 2.07], P < 0.00001) when compared with the control groups. However, there was no significant difference in the drop of Catherine Bergego Scale (CBS) and Behavioural Inattention Test-conventional (BIT-C) between the two groups. CONCLUSIONS: Acupuncture combined with rehabilitation was more effective in improving the motor function and the ability of daily living. Because of the limitations regarding the quantity and quality of the studies in this meta-analysis, high-quality and well-designed RCTs are necessary to validate the above conclusions.

Coenzyme Q10 suppresses oxidative stress and apoptosis via activating the Nrf-2/NQO-1 and NF-κB signaling pathway after spinal cord injury in rats.

Spinal cord injury (SCI) is one of the most devastating diseases that may cause paralysis, disability and irreversible loss of functions, which ultimately lead to permanent disabilities and a decrease in patient life expectancy. Coenzyme Q10 (CoQ10) is a lipid-soluble vitamin-like benzoquinone compound that can exert antioxidant and anti-apoptotic functions in a variety of diseases. However, the antioxidant and anti-apoptotic effects of CoQ10 in the treatment of SCI are still unknown. Therefore, we designed experiments to measure the changes in antioxidant capacity (glutathione (GSH), superoxide dismutase (SOD) and the end product of lipid peroxidation (MDA)) and apoptosis products (Bax, Bcl-2 and Caspase-3) to evaluate the protective effects of CoQ10 on SCI and investigated whether CoQ10 exerts its functions through the Nrf-2/NQO-1 and NF-κB signaling pathway. Our results showed that CoQ10 treatment could significantly decrease the levels of oxidative products (MDA) and increase the activities of antioxidant enzymes (SOD and GSH) against oxidative stress, as well as decrease the levels of pro-apoptotic proteins (Bax and Caspase-3) and increase the levels of anti-apoptotic proteins (Bcl-2) against apoptosis after SCI. We also observed that CoQ10 exerted beneficial effects through the Nrf-2/NQO-1 and NF-κB signaling pathway. These findings suggested that CoQ10 had a protective effect by decreasing oxidative stress and apoptosis after SCI. Thus, our data may provide a new approach wherein CoQ10 may be considered as a potential effective therapeutic for the treatment of SCI.

Research on Concrete Columns Reinforced with New Developed High-Strength Steel under Eccentric Loading.

The use of new developed high-strength steel in concrete members can reduce steel bar congestion and construction costs. This research aims to study the behavior of concrete columns reinforced with new developed high-strength steel under eccentric loading. Ten reinforced concrete columns were fabricated and tested. The test variables were the transverse reinforcement amount and yield strength, eccentricity, and longitudinal reinforcement yield strength. The failure patterns were compression and tensile failure for columns subjected to small eccentricity and large eccentricity, respectively. The same level of post-peak deformability and ductility could only be obtained with a lower amount of transverse reinforcement when high-strength transverse reinforcements were used in columns subjected to small eccentricity. The high-strength longitudinal reinforcement improved the bearing capacity and post-peak deformability of the concrete columns. Furthermore, three different equivalent rectangular stress block (ERSB) parameters for predicting the bearing capacity of columns with high-strength steel are discussed based on test and simulated results. It is concluded that the China Code GB 50010-2010 overestimates the bearing capacity of columns with high-strength steel, whereas the bearing capacities computed using the America Code ACI 318-14 and Canada Code CSA A23.3-04 agree well with the test results.

Huo Xue Tong Luo capsule ameliorates osteonecrosis of femoral head through inhibiting lncRNA-Miat.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has a long history of treating various bone diseases including osteoporosis and osteonecrosis etc. In clinical treatment, Huo Xue Tong Luo capsule (HXTL capsule) containing Peach kernel, Safflower carthamus, Angelica sinensis, Ligusticum wallichii etc, is one of the mostly used prescriptions for treating osteonecrosis of the femoral head (ONFH) with promising effects. OBJECTIVES: This study aims to identify the underlying molecular mechanism of how HXTL capsule exerts its function to ameliorate ONFH. MATERIALS AND METHODS: All femoral bone tissues were collected during surgeries. Rat bone marrow mesenchymal stem cells (rMSCs) were used. Quantitative real time PCR was used to check the relative expression levels of genes. ChIP assay was performed to evaluate the binding of H3K4me3 and H3K27me3 in Miat promoter. RESULTS: We showed that HXTL capsule promoted osteogenesis in rat MSCs as demonstrated by quantitative real time PCR and Alizarin Red S staining. Then we found silencing the endogenous lncRNA-Miat could promote osteogenesis of rMSCs. In addition, the ChIP assay showed that HXTL capsule significantly increased occupancy of H3K27me3 and decreased H3K4me3 in promoter regions of Miat, meaning HXTL capsule inhibited Miat expression through histone modifications. At last, by examining the femoral heads samples obtained from patients with ONFH during total hip arthroplasty surgery, we found the RNA level of hMiat in necrotic tissue was much higher than that of normal tissue. CONCLUSIONS: Taken together, our study shows that lncRNA-Miat might play an important role in pathogenesis of ONFH, and HXTL capsule can promote osteogenesis to ameliorate ONFH through inhibiting the transcriptional expression of Miat, at least partially.

Sox11-modified mesenchymal stem cells accelerate cartilage defect repair in SD rats.

Cartilage has a limited capacity to heal. Previously, we have shown that overexpression of Sox11 in rMSCs (Rat Mesenchymal Stem Cells) by lentivirus-mediated gene transfer leads to enhanced tri-lineage differentiation and accelerated bone formation in fracture model of rats. We observed that the fracture repair in the rats that received Sox11-modified rMSCs injection proceeded through an endochondral ossification process much faster than those in the control groups. However, the detailed role of Sox11 in rMSCs chondrogenic differentiation, as well as cartilage defect, is still not clearly clarified. Therefore, this study tests the hypothesis that Sox11 promotes chondrogenesis and cartilage defect repair by regulating ß-catenin. Sox11 was transduced into rMSCs using lentiviruses. The expression levels of ß-catenin and its downstream genes were evaluated by quantitative RT-PCR. The transcriptional activation of ß-catenin was proved by dual-luciferase reporter assay and co-immunoprecipitation was performed to evaluate Sox11-ß-catenin interaction. In addition, a cartilage defect model in SD rats was used to evaluate the cartilage regeneration ability of Sox11-modified rMSCs in vivo. We found that Sox11 transcriptionally activated ß-catenin expression and discovered the core promoter region (from - 242 to - 1414) of ß-catenin gene for Sox11 binding. In addition, Sox11 might regulate ß-catenin at the post-transcriptional level by protein-protein interaction. Finally, using a cartilage defect model in rats, we found Sox11-modified rMSCs could improve cartilage regeneration. Taken together, our study shows that Sox11 is an important regulator of chondrogenesis and Sox11-modified rMSCs may have clinical implication for accelerating cartilage defect healing.