Percutaneous Curved Vertebroplasty Versus Unipedicular Approach Vertebroplasty for Acute Osteoporotic Vertebral Compression Fractures : A Randomized Controlled Trial.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To clarify whether percutaneous curved vertebroplasty (PCVP) is superior to conventional unipedicular approach vertebroplasty (UVP) in patients with acute osteoporotic vertebral compression fractures (OVCFs). SUMMARY OF BACKGROUND DATA: Unilateral curved vertebroplasty devices were designed and applied to provide better control of cement placement, which may be superior to traditional UVP for the treatment of acute OVCFs. MATERIALS AND METHODS: Patients with single-level OVCFs of <6 weeks duration and visual analog scale (VAS) of back pain 5 or more were randomly allocated to undergo PCVP or UVP and were followed up for 1 year. The primary outcome was overall VAS scores for back pain during 12 months of follow-up. The secondary outcomes were scores on the Oswestry disability index at each postprocedure clinic visit. Radiographic (cement distribution) and surgical data (operation time, fluoroscopy frequency, and cement volume) were assessed. Complications and adverse events were recorded. RESULTS: No statistical difference was found between the PCVP and UVP groups with respect to VAS and Oswestry disability index scores at any follow-up time point. Operative time, fluoroscopy frequency, and cement leakage were similar in both groups, while the PCVP techniques had a larger injection of polymethylmethacrylate (5.5 ± 1.4 vs . 4.2 ± 1.0 mL) and a greater dispersion pattern of cement ( P < 0.001). Post hoc observations found that the analgesic effect was positively correlated with the symmetry of bone cement distribution, but not with the surgical method. Two serious adverse events occurred in the vertebroplasty group: one stress ulcer and one allergic reaction. CONCLUSIONS: Although PCVP achieved more symmetrical cement distribution, which seemed to be associated with a greater analgesic effect, PCVP did not result in significantly greater pain relief than a UVP in the 12 months after treatment.

Changes of adjacent segment biomechanics after anterior cervical interbody fusion with different profile design plate: single- versus double-level.

Low-profile angle-stable spacer Zero-P is claimed to reduce the morbidity associated with traditional plate and cage construct (PCC). Both Zero-P and PCC could achieve comparable mid- and long-term clinical and radiological outcomes in anterior cervical discectomy and fusion (ACDF). It is not clear whether Zero-P can reduce the incidence of adjacent segment degeneration (ASD), especially in multi-segmental fusion. This study aimed to test the effect of fusion level with Zero-P versus with PCC on adjacent-segment biomechanics in ACDF. A three-dimensional finite element (FE) model of an intact C2-T1 segment was built and validated. Six single- or double-level instrumented conditions were modeled from this intact FE model using Zero-P or the standard PCC. The biomechanical responses of adjacent segments at the cephalad and caudal levels of the operation level were assessed in terms of range of motion (ROM), stresses in the endplate and disc, loads in the facets. When comparing the increase of adjacent-segment motion in single-level PCC fusion versus Zero-P fusion, a significantly larger increase was found in double-level fusion condition. The fold changes of PCC versus Zero-P of intradiscal and endplate stress, and facet load at adjacent levels in the double-level fusion spine were significantly larger than that in the single-level fusion spine during the sagittal, the transverse, and the frontal plane motion. The increased value of biomechanical features was greater at above segment than that at below. The fold changes of PCC versus Zero-P at adjacent segment were most notable in flexion and extension movement. Low-profile device could decrease adjacent segment biomechanical burden compared to traditional PCC in ACDF, especially in double-level surgery. Zero-P could be a good alternative for traditional PCC in ACDF. Further clinical/in vivo studies will be necessary to explore the approaches selected for this study is warranted.

GSK 650394 Inhibits Osteoclasts Differentiation and Prevents Bone Loss via Promoting the Activities of Antioxidant Enzymes In Vitro and In Vivo.

Osteoporosis (OP) is one of the most common bone disorders among the elderly, characterized by abnormally elevated bone resorption caused by formation and activation of osteoblast (OC). Excessive reactive oxygen species (ROS) accumulation might contribute to the formation process of OC as an essential role. Although accumulated advanced treatment target on OP have been proposed in recent years, clinical outcomes remain unexcellence attributed to severe side effects. The purpose of present study was to explore the underlying mechanisms of GSK 650394 (GSK) on inhibiting formation and activation of OC and bone resorption in vitro and in vivo. GSK could inhibit receptor activator of nuclear-κB ligand (RANKL-)-mediated Oc formation via suppressing the activation of NF-κB and MAPK signaling pathways, regulating intracellular redox status, and downregulate the expression of nuclear factor of activated T cells c1 (NFATc1). In addition, quantitative RT-PCR results show that GSK could suppress the expression of OC marker gene and antioxidant enzyme genes. Consistent with in vitro cellular results, GSK treatment improved bone density in the mouse with ovariectomized-induced bone loss according to the results of CT parameters, HE staining, and Trap staining. Furthermore, GSK treatment could enhance the capacity of antioxidant enzymes in vivo. In conclusion, this study suggested that GSK could suppress the activation of osteoclasts and therefore maybe a potential therapeutic reagent for osteoclast activation-related osteoporosis.

Therapeutic Strategy of Percutaneous Transforaminal Endoscopic Decompression for Stenosis Associated With Adult Degenerative Scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effects of percutaneous transforaminal endoscopic decompression (PTED) for lumbar stenosis associated with adult degenerative scoliosis and to analyze the correlation between preoperative radiological parameters and postoperative surgical outcomes. METHODS: Two years of retrospective data was collected from 46 patients with lumbar stenosis associated with adult degenerative scoliosis who underwent PTED. The visual analog scale (VAS), Oswestry Disability Index, and modified MacNab criteria were used to evaluate the clinical outcomes. Multiple linear regression analysis was used to analyze the correlation between radiological parameters and surgical outcomes. RESULTS: The mean age of the 33 female and 13 male patients was 73.5 ± 8.1 years. The mean follow-up was 27.6 ± 3.5 months (range from 24 to 36). The average coronal Cobb angle was 24.5 ± 8.2°. There were better outcomes of the VAS for leg pain and Oswestry Disability Index after surgery. Based on the MacNab criteria, excellent or good outcomes were noted in 84.78% of patients. Multiple linear regression analysis showed that Cobb angle and lateral olisthy may be the predictors for low back pain. CONCLUSION: Transforaminal endoscopic surgery may be an effective and safe method for geriatric patients with lumbar stenosis associated with degenerative scoliosis. The predictive factors of clinical outcomes were severe Cobb angle and high degree lateral subluxation. Transforaminal endoscopic surgery may not be recommended for patients with Cobb angle larger than 30° combined with lateral subluxation.

Estrogen receptor ß/substance P signaling in spinal cord mediates antinociceptive effect in a mouse model of discogenic low back pain.

Introduction: Discogenic low back pain (DLBP) is the most commonly described form of back pain. Our previous studies indicated that estrogen-dependent DLBP mechanism was mediated by estrogen receptors (ERs) in the intervertebral disc (IVD) tissue, and the IVD degeneration degree is accompanied by downregulation of ERs, particularly ERß. However, the neuropathological mechanisms underlying ERs modulation of DLBP are still not well understood. In this study, we investigated the antinociceptive effects of selective ERß agonists on DLBP-related behavior by regulating substance P in spinal cord and dorsal root ganglia. Methods: Two weeks after ovariectomies, 18-week-old female mice were randomly separated into four groups: control group; DLBP sham surgery plus vehicle group; DLBP plus vehicle group; DLBP plus ERß-specific agonist diarylpropionitrile (DPN) group. Behavioral data was collected including behavioral measures of axial back pain (grip force and tail suspension tests) and radiating hypersensitivity (mechanical sensitivity and cold sensitivity test). Dual label scanning confocal immunofluorescence microscopy was used to observe spatial colocalization of ERß and substance P in spinal cord. Substance P changes in spinal cord and dorsal root ganglia were measured by immunohistochemistry and real-time PCR. Results: ERß activation could improve both axial and radiating behavioral disorders of DLBP. DPN facilitated the decrease of the amount of time in immobility 1 week after agonist administration. At the time point of 3 weeks, DPN group spent significantly less time in immobility than the vehicle group. In the grip strength tests, starting from postoperative week 1-week 3, DPN injection DLBP mice showed more resistance to stretch than the vehicle injection DLBP mice. Significant differences of cold withdrawal latency time were observed between the DLBP plus DPN injection and DLBP vehicle injection groups at 2- and 3-week injection time point. DPN significantly reversed the paw withdrawal threshold of DLBP mice at the time point of 1, 2, and 3 weeks. Substance P colocalized with ERß in spinal dorsal horn, mainly in laminae I and II, a connection site of pain transmission. Substance P levels in dorsal horn and dorsal root ganglia of DLBP group were distinctly increased compared with that of control and DLBP sham group. DPN therapy could decrease substance P content in the dorsal horn and the dorsal root ganglia of DLBP mice compared with that of vehicle-treated DLBP mice. Discussion: Activation of ERß is antinociceptive in the DLBP model by controlling substance P in spinal cord and dorsal root ganglia, which might provide a therapeutic target to manage DLBP in the clinic.

The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice.

The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman's analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERß antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.

UNC5B-AS1 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells via regulating miR-4306/KDM2A axis.

Being one of the most prevalent malignancies, hepatocellular carcinoma (HCC) threatens the health of population all over the world. Numerous researches have confirmed that long noncoding RNAs (lncRNAs) play an important role in tumor progression. Nonetheless, the mechanisms of unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1) in HCC remain obscure. Thus, this study aims to investigate the regulatory role and mechanism of UNC5B-AS1 in HCC cells. In our research, UNC5B-AS1 was subjected to gene expression analysis by RT-qPCR. Biological functions of UNC5B-AS1 in HCC cells were measured by MTT, colony formation, EdU and transwell assays. The combination between UNC5B-AS1, lysine demethylase 2A (KDM2A) and miR-4306 was validated by mechanism assays. Result showed UNC5B-AS1 was upregulated in HCC tissues and cells, contributing to the development of cancer staging and survival rate of HCC patients. Moreover, UNC5B-AS1 deficiency inhibited the proliferation, migration and epithelial-mesenchymal transition (EMT) of HCC cells. Furthermore, UNC5B-AS1 could interact with miR-4306 in HCC cells. Similarly, KDM2A was proved as the target gene of miR-4306. Finally, miR-4306 downregulation or KDM2A overexpression reversed the prohibitive role of UNC5B-AS1 knockdown in HCC progression. In short, UNC5B-AS1 accelerates the proliferation, migration and EMT of HCC cells via the regulation of miR-4306/KDM2A axis.

Impact of adjacent pre-existing disc degeneration status on its biomechanics after single-level anterior cervical interbody fusion.

BACKGROUND AND OBJECTIVE: Mechanics and biology may be interconnected and amplify each other during disc degeneration. It remains unknown the influence of pre-existing disc degeneration and its impact on adjacent segment degeneration (ASD) after anterior cervical discectomy and fusion (ACDF). This study aimed to discuss the necessity of including degenerated adjacent segments in single-level ACDF surgery from a biomechanical view. METHODS: A poroelastic C2-T1 finite element model was created and validated. A C5-C6 ACDF model was developed based on this normal model. Moderate C4-C5 disc degeneration was created by appropriately modifying the morphology and tissue material properties in this fusion model. Degenerative morphology was modeled based on Thompson's grading system and Walraevens's scoring system for cervical spine, including disc height, whole disc area, nucleus pulposus (NP) area, endplate sclerosis and curvature. Stresses in disc and endplate and loads in facet joint were computed under moment loads in the fusion models with normal and pre-existing degenerative disc condition. RESULTS: As for the adjacent disc, the stress values in degenerative condition were 7.41%, 5% and 5.26% larger than that in normal situation during extension, axial rotation and lateral bending motion, respectively. The disc stress changes mainly stemmed from annulus fibrosus (AF) tissue, but not NP. In the endplate, stress values of degeneration status were 4.17, 4.35 and 6.06% larger than that of normal condition under axial rotation, lateral bending and extension. The facet load magnitudes of pre-existing degeneration were 11.28, 11.57, 11.78 and 11.42% greater than that of normal condition in flexion, extension, axial rotation and lateral bending motion. CONCLUSION: Pre-existing degenerated disc experience increased biomechanical changes in adjacent segment after single-level ACDF. It may pose a long-term cumulative problem related to biomechanics in cervical spine after fusion. Before surgery, surgeons should be careful about selecting the fusion level.

Region-specific effects of blocking estrogen receptors on longitudinal bone growth.

Estrogen receptors (ERs) regulate the development of the growth plate (GP) by binding to estrogen, a phenomenon that determines the growth of skeletal bone. However, the exact mechanisms underlying the regulatory effects of ERs on axial and appendicular growth plates during puberty remain unclear. In the present study, the strategy of ERß blocking resulted in increased longitudinal elongation of the appendicular bone (P < 0.01), whereas ERα blocking suppressed appendicular elongation (P < 0.05). Blocking both ERs did not have opposite effects on axial longitudinal growth. The expression of chondrocyte proliferation genes including collagen II, aggrecan, and Sox9 and hypertrophic marker genes including collagen X, MMP13, and Runx2 was significantly increased in the growth plate of female mice treated with ERß antagonist compared with that in the GP of control mice (P < 0.05). There were no significant differences in local insulin-like growth factor 1 (IGF-1) expression among these groups (P > 0.05), and Indian hedgehog protein (Ihh) and parathyroid-related protein (PTHrP) expressions differed among these groups (P < 0.05). ERs appeared not to affect axial bone growth during puberty in female mice (P > 0.05). Our data show that the blocking of different ER subtypes might have a region-specific influence on longitudinal appendicular and axial growth.

Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc.

Intervertebral disc degeneration (IDD) is a main contributor to low back pain. A close relationship exists between inflammation and pain. Estrogen can affect inflammation and may play a crucial role in IDD and pain. Substance P (SP) can also regulate the expression of pro-inflammatory cytokines in intervertebral disc (IVD). This study aimed to investigate the potential role of SP in estrogen regulation of IDD. Nine-week-old C57BL/6 female mice were divided into four groups as follows: sham surgery (sham), ovariectomy (OVX), ovariectomy plus estrogen replacement therapy (ERT) group (OVX+E2), and ovariectomy, ERT plus neurokinin 1 receptor (NK1R) agonist (OVX+E2+G). Serum E2, body, and uterus weight were recorded. Immunohistochemistry study and quantitative real-time PCR were used for SP, NK1R, IL-1ß, IL-6, and TNF-α examination and comparison in IVD at protein and gene levels. After OVX, the gene and protein expression of TNF-α, IL-1ß, IL-6, SP, and NK1R in NP cells significantly increased compared with the sham group. ERT can reverse these impacts. ERT plays anti-inflammatory and anti-hyperalgesic roles in IDD of OVX mice. The estrogen-induced changes of the pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, are significantly inhibited by NK1R agonists. SP may be a mediator of estrogen regulating pro-inflammatory factors in IDD. Estrogen may affect IVD inflammation through two ways: one is to directly affect the level of pro-inflammatory cytokines and the other is by means of modulation of SP.

Adjacent-level biomechanics after single-level anterior cervical interbody fusion with anchored zero-profile spacer versus cage-plate construct: a finite element study.

BACKGROUND: The development of adjacent segment degeneration (ASD) following ACDF is well established. There is no analytical study related to effects of plate profile on the biomechanics of the adjacent-level after ACDF. This study aimed to test the effects of plate profile on the adjacent-level biomechanics after single-level anterior cervical discectomy and fusion (ACDF). METHODS: A three-dimensional finite element model (FEM) of an intact C2-T1 segment was built and validated. From this intact model, two instrumentation models were constructed with the anchored zero-profile spacer or the standard plate-interbody spacer after a C5-C6 corpectomy and fusion. Motion patterns, the stresses in the disc, the endplate, and the facet joint at the levels cephalad and caudal to the fusion were assessed. RESULTS: Compared with the normal condition, the biomechanical responses in the adjacent levels were increased after fusion. Relative to the intact model, the average increase of range of motion (ROM) and stresses in the endplate, the disc, and the facet of the zero-profile spacer fusion model were slightly lower than that of the standard plate-interbody spacer fusion model. The kinematics ROM and stress variations above fusion segment were larger than that below. The biomechanical features of the adjacent segment after fusion were most affected during extension. CONCLUSIONS: The FE analysis indicated that plate profile may have an impact on the biomechanics of the adjacent-level after a single-level ACDF. The impact may be long-term and cumulative. The current findings may help explain the decreasing incidence of ASD complications in the patients using zero-profile spacer compared with the patients using cage and plate construct.

Efficacy of percutaneous transforaminal endoscopic decompression treatment for degenerative lumbar spondylolisthesis with spinal stenosis in elderly patients.

The efficacy of fusion combined with decompression for the treatment of spinal stenosis with degenerative lumbar spondylolisthesis (DLS) has been debated. Percutaneous transforaminal endoscopic decompression (PTED) under local anesthesia is an ultra-minimally invasive procedure. The present study aimed to evaluate whether PTED is an effective alternative therapy for spinal stenosis associated with DLS in elderly patients. PTED was performed in elderly patients exhibiting lumbar stenosis and low-grade (Meyerding grades I and II) DLS; these patients also exhibited leg-dominant symptoms and had tolerable or absent mechanical back pain. Administration of general anesthesia may be considerably hazardous in patients when combined with comorbid conditions that result from aging. Therefore, the present procedure was performed under local anesthesia. No obvious radiographic lumbar intervertebral instability was identified prior to surgery. Pre- and post-operative visual analogue scale (VAS) score, Oswestry Disability Index (ODI) and walking distance data were collected. The clinical global outcomes following surgery were evaluated using modified MacNab criteria. A total of 18 elderly patients underwent surgery using PTED techniques. The mean follow-up time was 27.7 months (range, 24-33 months) and the mean estimated blood loss was 18.33 ml (range, 10-35 ml). The mean pre-operative ODI, VAS score of the back and VAS score of the leg were 68.2±6.5, 2.8±1.4 and 6.6±1.2, respectively. All average scores improved post-operatively to 31.7±5.2, 1.5±0.6 and 1.7±0.8, respectively, at the latest follow-up. A statistically significant improvement was observed for all scores at 1 month and that the scores remained relatively stable after that. According to modified MacNab criteria, the good-to-excellent rate was 83.3%. Only 1 patient required micro-decompression surgery due to poor rating. The present study indicated that PTED may be an effective alternative therapeutic option for elderly patients with low-grade DLS associated with spinal stenosis. However, PTED techniques continue to evolve and further follow-up studies are required to determine the long-term outcomes of this treatment technique.

The role of estrogen in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a main contributor to low back and radicular pain, which imposes heavy economic burdens on society. However, the etiology and mechanism of IVDD are complex and still not completely clear. In particular, the role of estrogen in IVDD has not received much attention in recent research, although estrogen plays a crucial role in the metabolic dysfunction of others musculoskeletal structures, such as bone, muscle, and tendon. In this review, we attempt to describe the role of estrogen in IVDD and to summarize the proposed mechanisms in vivo and in vitro, as well as, to outline several interesting questions in this field.

A c-di-AMP riboswitch controlling kdpFABC operon transcription regulates the potassium transporter system in Bacillus thuringiensis.

The intracellular K+ level in bacteria is strictly controlled by K+ uptake and efflux systems. Among these, KdpFABC is a high-affinity K+ transporter system that is generally activated by the KdpDE two-component system in response to K+ limitation stress. However, the regulatory mechanism remains obscure in bacteria lacking the kdpDE genes. Here we report that the transcription of a kdpFABC operon is distinctively regulated by a cyclic diadenylate monophosphate (c-di-AMP) riboswitch located at the 5'-untranslated region of kdp transcript, and binding of c-di-AMP to the riboswitch promotes its intrinsic termination that blocks the kdpFABC transcription. Further, the intracellular c-di-AMP concentration was found to decrease under the K+ limitation stress, leading to transcriptional read-through over the terminator to allow kdpFABC expression. This regulatory element is found predominantly in the Bacillus cereus group and correlate well with the K+ and c-di-AMP homeostasis that affects a variety of crucial cellular functions.

Endoscopic Ventral Decompression for Spinal Stenosis with Degenerative Spondylolisthesis by Partially Removing Posterosuperior Margin Underneath the Slipping Vertebral Body: Technical Note and Outcome Evaluation.

BACKGROUND: Decompression alone is a treatment option in patients with lumbar spinal stenosis (LSS) and degenerative lumbar spondylolisthesis (DLS). This study aims to describe the procedure of percutaneous transforaminal endoscopic ventral decompression technique and to demonstrate the clinical outcomes. METHODS: Two years of retrospective data were collected from 26 patients with predominant unilateral leg pain caused by LSS and low-grade DLS (Meyerding grades I and Ⅱ). All patients underwent endoscopic ventral decompression by removing the posterosuperior margin underneath the slipping vertebral body, combined with dorsal decompression without excessive resection of facet joints. The surgical outcomes were assessed using the visual analog scale (VAS), Oswestry Disability Index (ODI), modified MacNab criteria, and walking distance improvement evaluation. RESULTS: The mean age of the 18 women and 8 men was 69.2 years. The mean preoperative ODI and VAS of the leg and the back scores were 64.7 ± 8.1, 7.0 ± 1.4, and 3.0 ± 1.2, respectively. All mean scores improved postoperatively to 31.4 ± 5.6, 2.4 ± 1.1, and 1.7 ± 1.1 at the final follow-up. In 88.5% of cases, patients' estimated walking distance improved. The outcomes of the modified MacNab criteria showed that 81.3% of patients obtained good-to-excellent rate. There were no statistically significant differences between the percent slip of spondylolisthesis before surgery and at the end of follow-up. CONCLUSIONS: Based on the initial short-term follow-up results, transforaminal endoscopic ventral decompression by partially removing the posterosuperior margin underneath the slipping vertebral body, combined with dorsal decompression, might be an efficient alternative treatment for leg dominant symptoms in patients with LSS and low-grade DLS.

Retracted Article: Melatonin protects spinal cord injury by up-regulating IGFBP3 through the improvement of microcirculation in a rat model.

The present study was aimed at the investigation of the effects of melatonin on spinal cord injury (SCI) and the role of IGFBP3 in SCI both in vivo and in vitro. The rats received treatment with 100 mg kg-1 melatonin or both melatonin and pGenesil-1-si-IGFBP3 (50 µg per g bw) after SCI surgery. The motor function in rats was measured using the Basso-Beattie-Bresnahan (BBB) scale score; perfusion vessel area was determined by injecting FITC-conjugated lycopersicon esculentum agglutinin lectin (FITC-LEA), whereas the blood-spinal cord barrier permeability was measured using Evans blue. The pericytes were isolated, and the cells were cultured under hypoxia, treated with melatonin or transfected with si-IGFBP3. RT-qPCR and western blotting were conducted for the determination of IGFBP3, VEGF, MMP-2, ICAM-1 and Ang1. The expression of IGFBP3 was significantly down-regulated in the SCI rats, and melatonin significantly enhanced the IGFBP3 level. Melatonin improved the motor function, reduced the neuron injury, and improved the microcirculation in rats. However, the down-regulation of IGFBP3 significantly reversed these effects. Moreover, in both the SCI rat spinal cord tissues and the in vitro pericytes under hypoxia, the expressions of IGFBP3 and Ang1 were significantly down-regulated, whereas those of the proteins MMP-2, VEGF and ICAM-1 were significantly up-regulated, and melatonin dramatically inhibited these changes. Melatonin could protect the rats from SCI by improving the microcirculation through the up-regulation of IGFBP3.

Comparison of Effects of PELD and Fenestration in the Treatment of Geriatric Lumbar Lateral Recess Stenosis.

PURPOSE: Although degenerative lumbar spinal stenosis (LSS) is increasingly being diagnosed in older people, there is much uncertainty about the appropriate operative treatment options. The objective of this study was to compare the outcome of percutaneous endoscopic lumbar decompression (PELD) versus fenestration for lumbar lateral recess stenosis (LRS) in geriatric patients over 75 years old. MATERIALS AND METHODS: This prospective controlled study was performed on 46 consecutive over aged patients with lateral recess stenosis who underwent either PELD or fenestration. Clinical data were recorded before, 1 week, 3 months and 1.5 years after surgery using visual analog scale (VAS), Japanese Orthopaedic Association Score (JOA), The Short-Form-36 (SF-36), and the modified Macnab evaluation criteria. RESULTS: The patients' mean age was 82.7 years (aged 75-93 years) in PELD group and 79.1 years (aged 75-88 years) in fenestration group. No statistical difference was found between PELD group and fenestration group with regards to VAS-back pain, VAS-leg pain, JOA and at 3 months and 1.5-year follow-up. However, the PELD group had a lower mean VAS for back pain at 1 week postoperatively (P<0.05). The quality of life in PELD group achieved the same remarkable improvement as fenestration group (P>0.05). Operative time (min) was similar between two groups (p>0.05), while the PELD techniques brought advantages in blood loss (mL) (48.3 vs 128.2, p<0.05), early ambulation (h) (5.5 vs 25.2, p<0.05), and anesthesia-related complications. CONCLUSION: Both PELD and fenestration showed favorable clinical outcomes for the treatment of lumbar lateral recess stenosis. In addition, PELD had advantages such as reduced traumatization and less anesthesia-related complications. In terms of quality of life and complications after operation, PELD under local anesthesia could be an efficient supplement to conventional decompression surgery in geriatric patients with lumbar lateral recess stenosis.

The immunomodulatory peptide bursopentin (BP5) enhances proliferation and induces sIgM expression in DT40 cells.

BACKGROUND: In the recent past, many studies have been focused on extracts of BF and multiple biologically active factors and their effects on humoral immune system in chickens and birds. However, the mechanism of those immunomodulatory peptides on the B lineage cells proliferation and antibody production in chicken is fairly unknown. DT40 cell line, an avian leucosis virus-induced chicken pre-B cell line, expresses immunoglobulin M (IgM) isotype B cell reporter in the plasma membrane. There are many evidences suggesting that DT40 cells are best characterized as a bursal stem cell line. Because of the unique characteristics of DT40 cell line, it has been widely used to observe biological processes of pre-B lymphocyte cell within living cells. METHODS: The chicken B cell line DT40 was cultured in Roswell Park Memorial Institute (RPMI) 1640 medium and cytotoxicity was studied. Also, effect of BP5 on cell proliferation and cell cycle distribution of DT40 cells was studied. Also, the effect of BP5 on sIgM mRNA expression was studied by using real-time PCR. OBJECTIVES: To investigat the effects of Bursopentin (Cys-Lys-Arg-Val-Tyr, BP5) on a chicken promyelocyte cell line DT40, assays of cell proliferation, cell cycle distribution, detection of surface immunoglobulin G (sIgM) mRNA expression and gene microarray analysis were performed. RESULTS: The results showed that BP5 displayed concentration-dependent effects on the proliferation, cell cycle, and sIgM mRNA expression in DT40 cells. And the analysis of expression profiles identified a signature set of 3022 genes (1254 up regulated genes, 1762 down regulated genes), which clearly discriminated the BP5-treated DT40 cells from control with high certainty (P≤0.02). The results of microarray analysis were confirmed by quantitative reverse transcription-polymerase chain reaction for 12 of the differentially expressed genes. CONCLUSION: Theses findings showed the immuno-activity effect of BP5 on B lymphocyte and indicated that BP5 treatment regulated eight signaling pathways, in which Toll-like signaling pathway was the most significant enrichment pathway.

Estradiol Alleviates Intervertebral Disc Degeneration through Modulating the Antioxidant Enzymes and Inhibiting Autophagy in the Model of Menopause Rats.

OBJECTIVE: To investigate the effects of menopause on redox balance in the intervertebral disc and to examine whether oxidative stress and autophagy were associated with disc degeneration in menopause rats. METHODS: Thirty female Sprague-Dawley rats were randomly divided into three groups (sham, ovariectomized with vehicle, and ovariectomized with estrogen). At the end of the 3-month treatment, the rats were examined by 3.0 T MRI. Serum estradiol (E2) level was measured. Redox balance of nucleus pulposus was determined by measuring total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), and oxidized glutathione (GSSG). Transmission electron microscopy (TEM), immunohistochemical staining, and Western blot were used to determine the nucleus pulposus autophagy level. At the same time, Spearman's correlation coefficient was used to describe the relationship between intervertebral disc grade, oxidative stress status, serum E2, and autophagy level. RESULTS: The level of serum E2 was significantly decreased by ovariectomy and can be corrected by the estrogen replacement therapy (ERT). In OVX rats, an increased oxidative stress and high level of autophagy were observed in nucleus pulposus tissue. ERT prevented the intervertebral disc degeneration (IVDD), restored the redox balance, and reduced autophagy level. CONCLUSION: Ovariectomy induced oxidative stress, autophagy, and intervertebral disc degeneration. Autophagy of the intervertebral disc was negatively correlated with oxidative stress, and the level of autophagy can be reduced by ERT through modulating the redox balance and downregulating the autophagy level. Regulating the redox balance of IVD may be a potential therapeutic option for degeneration of the disc in the postmenopausal women.

Regulation of osteogenic differentiation by DNA methylation of the dishevelled gene in bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) are stem cells with multidirectional differentiation potential, which can be used as seed cells to repair and reconstruct many types of tissues and organs following injury or disease. Osteogenic differentiation involves a variety of pathway and factors, including cytokines, growth factors, and hormones. In the present study, we investigated the potential role of Dishevelled in osteogenic differentiation of BMSCs in induction medium containing the methyltransferase inhibitor 5-aza-2'-deoxycytidine. The expression of Dishevelled was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) and a Western blot. The methylation degree of the CpG island in the promoter region of the Dishevelled gene was analyzed, and protein expression levels of Wnt, Glycogen synthase kinase-3 (GSK3), axin, Dishevelled, and ß-catenin were increased after the addition of the methyltransferase inhibitor. The expression of Dishevelled increased in accordance with the differentiation of osteoblasts, and the degree of methylation of the promoter affected its expression level. In conclusion, regulating the methylation degree of the Dishevelled gene promoter region appears to influence the expression of Dishevelled and therefore the osteogenic differentiation of BMSCs.