Bioactive prenylated c6-c3 derivatives from the roots of Illicium brevistylum.

Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.

A biphasic calcium phosphate/acylated methacrylate gelatin composite hydrogel promotes osteogenesis and bone repair.

PURPOSE/AIM: Bone defects caused by trauma, tumors, congenital malformation, or inflammation are very common in orthopedics. In recent years, mimicking the composition and structure of natural bone tissue has become a hot topic in biomaterial research, with the aim of developing an ideal biomaterial for bone defect transplantation. Here, the feasibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel to repair bone defects was evaluated in vitro and in rats. MATERIALS AND METHODS: The biocompatibility of a biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel was evaluated by cytoskeleton staining, live/dead cell staining and cell proliferation assays. The in vitro osteogenic activities of the composite hydrogel were evaluated by alkaline phosphatase and alizarin red staining, as well as osteogenic gene expression analysis at both transcript and protein levels. The in vivo bone repair activities were evaluated using the rat skull defect model. RESULTS: The BCP/GelMA composite hydrogel displayed excellent biocompatibility and promoted osteogenesis of bone marrow mesenchymal stem cells in vitro. In addition, the BCP/GelMA composite hydrogel markedly promoted new bone formation in the rat skull-defect model. CONCLUSIONS: BCP/GelMA composite hydrogel may be an effective artificial material for bone tissue engineering.

Effect of Different Anesthesia and Puncture Methods of Percutaneous Kyphoplasty on More Than 90-Year-Old Osteoporotic Vertebral Fracture: Advantages of the ERAS Concept.

Background: Percutaneous kyphoplasty (PKP) is an effective minimally invasive technique for the treatment of osteoporotic vertebral fracture (OVF) in recent years. This study focuses on the analysis of PKP surgery and anesthesia in osteoporotic vertebral facture patients over 90 years old with the concept of "enhanced recovery after surgery." Methods: This study reviewed 239 patients who were diagnosed with OVF retrospectively between October 2015 and June 2019. According to the method of anesthesia, these patients were divided into Group A (n = 125) and Group B (n = 114). According to the pedicle puncture approach, these patients were divided into Group C (n = 102) and Group D (n = 137). The anterior vertebral height (AVH) and local kyphosis angle (LKA) were used to evaluate the degree of vertebral damage and restoration. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) scores were used for assessing functional outcomes. Some parameters were used to assess the perioperative conditions such as operation time, amount of bone cement perfusion, intraoperative fluoroscopy times, anesthesia recovery time, time out of the bed, hospital stay, hospitalization cost, and complications. Results: The visual analogue scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height (AVH), and local kyphosis angle (LKA) 1 day, 1 year after surgery, and at the last follow-up all showed significant improvement (P < 0.05) in comparison with those before surgery both in Groups A and B and Groups C and D. The ODI 1 day after surgery was significantly better in Group B than Group A (P < 0.05). Compared with Group B, Group A required longer time of anesthesia, operation time, anesthesia recovery time, time to get out of bed, and length of hospital stay and more hospitalization costs (P < 0.05). Group D required longer operation time, longer time to get out of bed, more bone cement volume, fluoroscopy time, and more operation hospitalization costs compared with Group C (P < 0.05). Conclusion: We recommend unilateral puncture under local anesthesia for OVF in the patients aged over 90 from the perspective of rapid recovery.

Outcome of percutaneous compression plate for treatment of femoral neck fractures: mean follow-up of 4.4 years.

PURPOSE: Percutaneous compression plate (PCCP) provides superior anti-rotational abilities and mechanical strength in femoral neck fractures (FNFs). The first series reporting its utilization of FNFs was promising. Since the long-term outcome regarding the implant has not been reported, the purpose of this study was to evaluate the long-term functional outcomes and complications after fixation using PCCP in FNFs. MATERIALS AND METHODS: From 2010 to 2019, 51 patients aged from 18 to 87 years were evaluated; 11 patients were excluded from this study. Demographic data, fracture classification, and complications were analyzed. Besides plain radiographs and CT, uptake ratios using bone scintigraphy and/or SPECT were also collected and analyzed. RESULTS: At a mean follow-up of 4.4 ± 2.0 years (range, 2-10 years), the mean Harris hip score was 88, with 44 patients (86.3%) achieving excellent or good outcomes. The rate of complication was 13.7% (7/51), with five cases of osteonecrosis of the femoral head (OFNH). Hip replacements were performed in four (7.8%) cases. After confirmation of normal transfusion status, 11 patients underwent elective removal of the implant without further complications. CONCLUSION: Closed reduction and internal fixation using PCCP in FNFs resulted in satisfactory outcomes with low complication rates. Longer follow-up (3-5 years) and sequential bone scintigraphy or SPECT after surgery are recommended after internal fixation using PCCP.

[Effect of Laportea bulbifera extract on CYP450 enzyme activities in rats by Cocktail probe drug method].

The Cocktail probe drug method was used to evaluate the effect of Laportea bulbifera extract on the different subtypes of CYP450 enzyme activities in rats, and to provide references for its clinical rational drug use. The rats were randomly divided into a high-dose L. bulbifera group(0.45 g·kg~(-1)·d~(-1)) and a low-dose L. bulbifera group(0.09 g·kg~(-1)·d~(-1)). After continuous gavage for 7 and 14 days, the Cocktail probe mixing solution, including caffeine, midazolam, tolbutamide, omeprazole, metoprolol, and chlorzoxazone, was injected into the tail vein, and the blood sample was obtained from the tail vein at different time points. Ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS) was established to determine the concentration of six probe drugs in rat plasma. DAS 2.0 was used to calculate its pharmacokinetic parameters, and the effect of L. bulbifera extract on CYP1 A2, CYP2 C9, CYP2 C19, CYP2 D6, CYP2 E1, and CYP3 A4 in rats was investigated. As compared with the blank control group, under the omeprazole index, the AUC_(0-t) and AUC_(0-∞) of the 7-day administration groups and the 14-day high-dose group were significantly decreased, and the CLz and Vz were significantly increased. Under the midazolam index, the AUC_(0-t) and AUC_(0-∞) of the 7-day low-dose group and the 14-day administration group were significantly decreased, and the CLz was significantly increased. In addition, the AUC_(0-∞) of the 7-day high-dose group was also significantly decreased. Under the index of metoprolol, the AUC_(0-t) and AUC_(0-∞) of each experimental group were decreased significantly, and the CLz and Vz of the 7-day low-dose group and the 14-day low-dose group were increased significantly. Under the caffeine index, the AUC_(0-t) and AUC_(0-∞) of the 7-day administration groups were increased significantly, the CLz was decreased significantly, and the t_(1/2 z) of the 14-day high-dose group was increased significantly. Under the chlorzoxazone index, the AUC_(0-t) and AUC_(0-∞) of the 7-day low-dose group were increased significantly, and the CLz was decreased significantly. Under the tolbutamide index, there was no statistical difference in the pharmacokinetic parameters. In conclusion, L. bulbifera extract induces the activities of CYP2 C19, CYP3 A4, and CYP2 D6, inhibits the activities of CYP1 A2 and CYP2 E1, and does not affect the activity of CYP2 C9.

Effects of different pedicle screw insertion depths on sagittal balance of lumbar degenerative spondylolisthesis, a retrospective comparative study.

BACKGROUND: Few reports to date have evaluated the effects of different pedicle screw insertion depths on sagittal balance and prognosis after posterior lumbar interbody and fusion (PLIF) in patients with lumbar degenerative spondylolisthesis (LDS). METHODS: A total of 88 patients with single-level PLIF for LDS from January 2018 to December 2019 were enrolled. Long screw group (Group L): 52 patients underwent long pedicle screw fixation (the leading edge of the screw exceeded 80% of the anteroposterior diameter of vertebral body). Short screw group (Group S): 36 patients underwent short pedicle screw fixation (the leading edge of the screw was less than 60% of the anteroposterior diameter of vertebral body). Local deformity parameters of spondylolisthesis including slip degree (SD) and segment lordosis (SL), spino-pelvic sagittal plane parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL), Oswestry Disability Index (ODI), and Visual Analog Scale (VAS) for back pain of both groups were compared. Postoperative complications, including vertebral fusion rate and screw loosening rate, were recorded. RESULTS: Except that PI in Group S at the final follow-up was not statistically different from the preoperative value (P > 0.05), other parameters were significantly improved compared with preoperative values one month after surgery and at the final follow-up (P < 0.05). There was no significant difference in parameters between Group L and Group S before and one month after surgery (P > 0.05). At the final follow-up, SD, SL, LL, PT and PI-LL differed significantly between the two groups (P < 0.05). Compared with the preoperative results, ODI and VAS in both groups decreased significantly one month after surgery and at the final follow-up (P < 0.05). Significant differences of ODI and VAS were found between the two groups at the final follow-up (P < 0.05). Postoperative complications were not statistically significant between the two groups (P > 0.05). CONCLUSIONS: PLIF can significantly improve the prognosis of patients with LDS. In terms of outcomes with an average follow-up time of 2 years, the deeper the screw depth is within the safe range, the better the spino-pelvic sagittal balance may be restored and the better the quality of life may be.

Percutaneous vertebroplasty versus kyphoplasty for the treatment of neurologically intact osteoporotic Kümmell's disease.

BACKGROUND: Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used to treat neurologically intact osteoporotic Kümmell's disease (KD), but it is still unclear which treatment is more advantageous. Our study aimed to compare and investigate the safety and clinical efficacy of PVP and PKP in the treatment of KD. METHODS: The relevant data that 64 patients of neurologically intact osteoporotic KD receiving PVP (30 patients) or PKP (34 patients) were analyzed. Surgical time, operation costs, intraoperative blood loss, volume of bone cement injection, and fluoroscopy times were compared. Occurrence of cement leakage, transient fever and re-fracture were recorded. Universal indicators of visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated separately before surgery and at 1 day, 6 months, 1 year, 2 years and the final follow-up after operation. The height of anterior edge of the affected vertebra and the Cobb's angle were assessed by imaging. RESULTS: All patients were followed up for at least 24 months. The volume of bone cement injection, intraoperative blood loss, occurrence of bone cement leakage, transient fever and re-fracture between two groups showed no significant difference. The surgical time, the operation cost and fluoroscopy times of the PKP group was significantly higher than that of the PVP group. The post-operative VAS, ODI scores, the height of the anterior edge of the injured vertebrae and kyphosis deformity were significantly improved in both groups compared with the pre-operation. The improvement of vertebral height and kyphosis deformity in PKP group was significantly better than that in the PVP group at every same time point during the follow-up periods, but the VAS and ODI scores between the two groups showed no significant difference. CONCLUSION: PVP and PKP can both significantly alleviate the pain of patients with KD and obtain good clinical efficacy and safety. By contrast, PKP can achieve better imaging height and kyphosis correction, while PVP has the advantages of shorter operation time, less radiation volume and operation cost.

Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients.

Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (HR), 1.17 (95% CI, 0.95-1.44), P =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted HR, 1.23 (95% CI, 0.98-1.55), P = 0.075 in TG increase group; 0.78 (95% CI, 0.57-1.07), P = 0.123 in LDL-C increase group; and 1.12 (95% CI, 0.9-1.39), P = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.

Telomerase Reverse Transcriptase and p53 Regulate Mammalian Peripheral Nervous System and CNS Axon Regeneration Downstream of c-Myc.

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.

Inhibition of PTEN activity promotes IB4-positive sensory neuronal axon growth.

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.

c-Myc controls the fate of neural progenitor cells during cerebral cortex development.

The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.

Sensory nerves protect from the progression of early stage osteoarthritis in mice.

PURPOSE: Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice. MATERIALS AND METHODS: OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression. RESULTS: Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group. CONCLUSIONS: Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

Transcriptome analysis of the dimorphic transition induced by pH change and lipid biosynthesis in Trichosporon cutaneum.

Trichosporon cutaneum, a dimorphic oleaginous yeast, has immense biotechnological potential, which can use lignocellulose hydrolysates to accumulate lipids. Our preliminary studies on its dimorphic transition suggested that pH can significantly induce its morphogenesis. However, researches on dimorphic transition correlating with lipid biosynthesis in oleaginous yeasts are still limited. In this study, the unicellular yeast cells induced under pH 6.0-7.0 shake flask cultures resulted in 54.32% lipid content and 21.75 g/L dry cell weight (DCW), so lipid production was over threefold than that in hypha cells induced by acidic condition (pH 3.0-4.0). Furthermore, in bioreactor batch cultivation, the DCW and lipid content in unicellular yeast cells can reach 21.94 g/L and 58.72%, respectively, both of which were also more than twofold than that in hypha cells. Moreover, the activities of isocitrate dehydrogenase (IDH), malic enzyme (MAE), isocitrate lyase (ICL) and ATP citrate lyase (ACL) in unicellular cells were all higher than in the hyphal cells. In the meanwhile, the transcriptome data showed that the genes related to fatty acid biosynthesis, carbon metabolism and encoded Rim101 and cAMP-PKA signaling transduction pathways were significantly up-regulated in unicellular cells, which may play an important role in enhancing the lipid accumulation. In conclusion, our results provided insightful information focused on the molecular mechanism of dimorphic transition and process optimization for enhancing lipid accumulation in T. cutaneum.

Structure and mechanical properties of high-weight-bearing and low-weight-bearing areas of hip cartilage at the micro- and nano-levels.

BACKGROUND: Articular cartilage has a high-weight-bearing area and a low-weight-bearing area, the macroscopic elastic moduli of the two regions are different. Chondrocytes are affected by the applied force at the microscopic level. Currently, the modulus of the two areas at the micro and nano levels is unknown, and studies on the relationship between macro-, micro- and nano-scale elastic moduli are limited. Such information may be important for further understanding of cartilage mechanics. Moreover, the surface morphology, proteoglycan content, and micro and nano structure of the two areas, which influences the mechanical properties of cartilage should be discussed. METHODS: Safranin-O/Fast Green staining was used to evaluate the surface morphology and semi-quantify proteoglycan content of porcine femoral head cartilage between the two weight-bearing areas. The unconfined compression test was used to determine the macro elastic modulus. Atomic force microscope was used to measure the micro and nano compressive elastic modulus as well as the nano structure. Scanning electron microscope was employed to evaluate the micro structure. RESULTS: No significant differences in the fibrillation index were observed between two areas (P = 0.5512). The Safranin-O index of the high-weight-bearing area was significantly higher than that of the low-weight-bearing area (P = 0.0387). The compressive elastic modulus of the high-weight-bearing area at the macro and micro level was significantly higher than that of the low-weight-bearing area (P = 0.0411 for macro-scale, and P = 0.0001 for micro-scale), while no statistically significant differences were observed in the elastic modulus of collagen fibrils at the nano level (P = 0.8544). The density of the collagen fibers was significantly lower in the high-weight-bearing area (P = 0.0177). No significant differences were observed in the structure and diameter of the collagen fibers between the two areas (P = 0.7361). CONCLUSIONS: A higher proteoglycan content correlated with a higher compressive elastic modulus of the high-weight-bearing area at the micro level than that of the low-weight-bearing area, which was consistent with the trend observed from the macroscopic compressive elastic modulus. The weight-bearing level was not associated with the elastic modulus of individual collagen fibers and the diameter at the nano level. The micro structure of cartilage may influence the macro- and micro-scale elastic modulus.

Excessive swelling of nerve roots : Important factor for recurring sciatica after lumbar surgery.

OBJECTIVE: The aim of the study was to investigate the occurrence of unexpectedly swollen nerve roots and to investigate the relationship between nerve root edema and recurrent radicular pain. METHODS: During the period from August 2010 to August 2015, a total of 462 patients with degenerative lumbar disease underwent surgery in this study group. Magnetic resonance imaging (MRI) was used to evaluate the details of the nerve root. Of the patients with recurring radiating pain 13 met the inclusion criteria of the study group and 24 patients without any complications volunteered as the control group. The visual analog scale (VAS), Oswestry Disability Index (ODI), and medical outcomes study item short form health survey (SF-36) were used to evaluate the clinical outcomes. RESULTS: The preoperative diameter of the nerve root showed no significant difference between the two groups (P = 0.28). The postoperative nerve diameter of the study group was larger than that of the control group (P < 0.01). The initial operation improved the symptoms and the VAS was significantly decreased (P < 0.01). After recurrence of the neuralgia, the VAS score significantly increased (P < 0.01). The pain of the study group improved to the same level as that of the control group 4 weeks after subsequent surgery (P = 0.47), while the quality of life was still lower than that of the control group (P < 0.05). The scores collected 3 months after surgery showed that the clinical outcomes were not different between the two groups (P > 0.05). CONCLUSION: In surgery for degenerative lumbar disease accompanied by nerve root edema, excessive nerve root swelling is an important factor for recurrent radiating pain. With a properly carried out intervention in the re-exploration, the recurrent symptoms can be gradually relieved.

Regulation of adult mammalian intrinsic axonal regeneration by NF-κB/STAT3 signaling cascade.

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.

Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone.

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+ ) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.

Intervertebral disc degeneration induced by long-segment in-situ immobilization: a macro, micro, and nanoscale analysis.

BACKGROUND: Cervical spine fixation or immobilization has become a routine treatment for spinal fracture, dislocation, subluxation injuries, or spondylosis. The effects of immobilization of intervertebral discs of the cervical spine is unclear. The goal of this study was to evaluate the effects of long-segment in-situ immobilization of intervertebral discs of the caudal vertebra, thereby simulating human cervical spine immobilization. METHODS: Thirty-five fully grown, male Sprague-Dawley rats were used. Rats were randomly assigned to one of five groups: Group A, which served as controls, and Groups B, C, D, and E, in which the caudal vertebrae were in-situ immobilized using a custom-made external device that fixed four caudal vertebrae (Co7-Co10). After 2 weeks, 4 weeks, 6 weeks, and 8 weeks of in-situ immobilization, the caudal vertebrae were harvested, and the disc height, the T2 signal intensity of the discs, disc morphology, the gene expression of discs, and the structure and the elastic modulus of discs was measured. RESULTS: The intervertebral disc height progressively decreased, starting at the 6th week. At week 6 and week 8, disc degeneration was classified as grade III, according to the modified Pfirrmann grading system criteria. Long-segment immobilization altered the gene expression of discs. The nucleus pulposus showed a typical cell cluster phenomenon over time. The annulus fibrosus inner layer began to appear disordered with fissure formation. The elastic modulus of collagen fibrils within the nucleus pulposus was significantly decreased in rats in group E compared to rats in group A (p < 0.05). On the contrary, the elastic modulus within the annulus was significantly increased in rats in group E compared to rats in group A (p < 0.05). CONCLUSION: Long-segment in-situ immobilization caused target disc degeneration, and positively correlated with fixation time. The degeneration was not only associated with changes at the macroscale and microscale, but also indicated changes in collagen fibrils at the nanoscale. Long-segment immobilization of the spine (cervical spine) does not seem to be an innocuous strategy for the treatment of spine-related diseases and may be a predisposing factor in the development of the symptomatic spine.

Analysis of Pre- and Postoperative Pain Variation in Osteoporotic Vertebral Compression Fracture Patients Undergoing Kyphoplasty.

BACKGROUND Balloon kyphoplasty (KP) has been widely applied in the treatment of elderly patients with osteoporosis vertebral compression fracture (OVCF), but there has been little research on the pain relief effect. Therefore, we performed this study of patients who received KP. The study included a set of fluoroscopy tests and follow-up evaluation, which aimed to verify the effectiveness of kyphoplasty in controlling back pain associated with OVCFs. MATERIAL AND METHODS Forty-three OVCF patients underwent kyphoplasty: 21 were allocated to an intervention group and 22 were allocated to a control group, and the 2 groups received treatment with different KP instruments. The variation of vertebral height was measured on X-ray and change of signal of MRI was recorded. The pain was assessed by VAS score and diagram, and physical function was evaluated by ODI. The complications after surgery were recorded and collated during 2 years of follow-up. RESULTS The intervention group showed no significant difference on the VAS and ODI compared to the control group (p>0.05). There was no difference in the VAS with different degrees of radiological change (p>0.05). Signal change on MRI imaging was rare. CONCLUSIONS Kyphoplasty is a positive way to alleviate early-onset OVCF pain. The change of BME extent in the treated level is unrelated to the relief of back pain after KP.

Percutaneous Balloon Kyphoplasty in Treatment of Painful Osteoporotic Occult Vertebral Fracture: A Retrospective Study of 89 Cases.

BACKGROUND The definition of a vertebral fracture is usually based on the presence of a deformation of the vertebral body and this can be misleading in the presence of a fracture without radiologic collapse with the definition of occult osteoporotic vertebral fractures (OOVFs). STIR sequence of MRI images showing hyperintensity signal was the most confirmative screening examination used to determine the presence of painful OOVFs. To date, clinical management of OOVFs has been rarely discussed. MATERIAL AND METHODS Between 2011 and 2013, 89 patients suffering from painful OOVFs underwent 142 percutaneous balloon kyphoplasty (PKP) procedures. Outcome data (mean variation of anterior and middle vertebral body height, visual analog scale [VAS] scores, Oswestry Disability Index [ODI] scores, and SF-36 scores) were recorded preoperatively, postoperatively, and at 1 month, 6 months, and 2 year after treatment, to evaluate the results. RESULTS We successfully treated 89 patients (142 vertebral bodies) with PKP. Cement leakages were observed in 12 (8.45%) treated vertebral bodies and there were 5 new adjacent vertebral fractures during the follow-up period. The mean variation of anterior and middle vertebral body height changed from 96.5±3.4% preoperatively to 97.2±2.5% postoperatively (p>0.05) and from 96.3±2.8% preoperatively to 97.9±3.1% postoperatively (p>0.05), respectively. The mean VAS scores were reduced significantly from pre-surgery to post-surgery (8.3±1.2 to 2.9±0.7; p<0.05), as was the ODI score (76.4±12.5 to 26.7±5.6; p<0.05). The SF-36 scores, including Bodily Pain (BF), Vitality (VT), Physical Function (PF), and Social Functioning (SF), all showed notable improvement (P<0.05). These variations were maintained during the 2-year follow-up period. CONCLUSIONS PKP is a safe and effective method in the treatment of painful OOVFs.