Intradiscal cement leakage (ICL) increases the stress on adjacent vertebrae after kyphoplasty for osteoporotic vertebra compression fracture (OVCF): a finite-element study.

This study aimed to explore the biomechanical effects on adjacent vertebra of thoracolumbar Osteoporotic Vertebra Compression Fracture (OVCF) after Percutaneous Kyphoplasty (PKP) with intraoperative intradiscal cement leakage (ICL) by applying a Finite-Element Analysis. We collected pre- and post-operative computer tomography (CT) images of a 71-year-old female patient with single T12 OVCF, who underwent an intraoperative cement leakage into the T12-L1 disc. Three-dimensional finite element models of thoracolumbar spine (T10-L2) were built with the support of Materialise Interactive Medical Image Control System (MIMICS) and ABAQUS software. The stress on adjacent vertebrae and endplates under the uniform compressive pressure (0.3 MPa) and during different loading moments were analyzed. The three-dimensional finite element models reveal an asymmetrical distribution of von Mises stresses on the adjacent endplate unaffected by the surgical intervention. The maximum von Mises stress on adjacent vertebral bodies increased during different loading conditions, especially for lateral bending and rotation loading conditions, whereas the maximum von Mises stress on distal non-treated vertebrae decreased on anteflexion and backward extension loading conditions. Post-operative adjacent vertebra compression fractures after PKP with intraoperative intradiscal cement leakage (ICL) may be closely related to the biomechanical changes of adjacent vertebrae of thoracolumbar OVCF, and it may increase the risk of postoperative fracture.

RpS3 Is Required for Spermatogenesis of Drosophila melanogaster.

Ribosomal proteins (RPs) constitute the ribosome, thus participating in the protein biosynthesis process. Emerging studies have suggested that many RPs exhibit different expression levels across various tissues and function in a context-dependent manner for animal development. Drosophila melanogaster RpS3 encodes the ribosomal protein S3, one component of the 40S subunit of ribosomes. We found that RpS3 is highly expressed in the reproductive organs of adult flies and its depletion in male germline cells led to severe defects in sperm production and male fertility. Immunofluorescence staining showed that RpS3 knockdown had little effect on early germ cell differentiation, but strongly disrupted the spermatid elongation and individualization processes. Furthermore, we observed abnormal morphology and activity of mitochondrial derivatives in the elongating spermatids of RpS3-knockdown testes, which could cause the failure of axoneme elongation. We also found that RpS3 RNAi inhibited the formation of the individualization complex that takes charge of disassociating the spermatid bundle. In addition, excessive apoptotic cells were detected in the RpS3-knockdown testes, possibly to clean the defective spermatids. Together, our data demonstrated that RpS3 plays an important role in regulating spermatid elongation and individualization processes and, therefore, is required for normal Drosophila spermatogenesis.

AMPK-SIRT1-PGC1α Signal Pathway Influences the Cognitive Function of Aged Rats in Sevoflurane-Induced Anesthesia.

To understand the effect of AMP-activated protein kinase (AMPK)-SIRT1 (silent information regulator 1)-PPARγ coactivator-1α (PGC1α) signaling pathway on the cognitive function of sevoflurane-anesthetized aged rats. Aged rats were divided into Normal group, Sevo group (Sevoflurane anesthesia), Sevo + AICAR (the AMPK activator) group, Sevo + EX527 group (the AMPK inhibitor), and Sevo + AICAR + EX527 group. The cognitive function of rats was determined by the Morris water maze. Hippocampal neuronal apoptosis was evaluated by TUNEL and Fluoro-Jade C (FJC) staining, and the expression of cleaved caspase-3 was detected by immunohistochemistry. ROS, SOD, and MDA levels and the fluorescence intensity of GFAP in the hippocampus were assayed. The mitochondrial membrane potential (MMP), mitochondrial mass, ATP level, and the expression of AMPK-SIRT1-PGC1α were determined by the corresponding methods. Rats in the Sevo group manifested significant extension in the escape latency, with fewer platform crossings; and meanwhile, the apoptotic rate, the number of FJC-positive cells, and the fluorescence intensity of GFAP of neurons were elevated, with up-regulation of cleaved caspase-3. Moreover, the level of MDA and ROS was increased evidently, with significant down-regulation of SOD activity, ATP, mitochondrial mass and MMP levels, and AMPK, SIRT1 and PGC-1α protein expressions. However, sevoflurane-induced changes above were improved after the administration of AICAR, and EX527 could reverse AICAR-induced improvements in Sevo-anesthetized aged rats. Activating AMPK-SIRT1-PGC1α pathway can improve the cognitive function and mitigate the neuronal injury in Sevo-anesthetized aged rats by antagonizing the oxidative stress and maintaining the mitochondrial function.

Correlations of Cerebrospinal Fluid/Plasma Fibroblast Growth Factor 21 Ratio with Metabolic Parameters in Chinese Individuals of Normal Weight.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is an important metabolic regulator that has multiple beneficial effects on glucose homeostasis and lipid metabolism. Although circulating levels of FGF21 are mainly derived from liver, FGF21 is also found in other tissues and fluids including the cerebrospinal fluid (CSF). The aim of the present study was to investigate the relationships of CSF and/or plasma FGF21 levels with metabolic parameters in a normal-weight Chinese population. METHODS: Forty-five subjects (22 males and 23 females) were recruited from a patient population undergoing surgery for lower extremity injuries due to ligament damage or bone fractures below the knee in the Beijing Jishuitan Hospital. The levels of FGF21 in CSF and plasma were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant differences were detected in the levels of FGF21 in CSF and plasma between males (CSF: 158.01 ± 12.10 pg/mL; plasma: 206.19 ± 7.22 pg/mL) and females (CSF: 159.27 ± 17.85 pg/mL; plasma: 203.10 ± 7.53 pg/mL). The level of FGF21 in CSF was about 75% of that in plasma. The FGF21 level in CSF was positively correlated with triglyceride level, whereas plasma FGF21 level was negatively correlated with alanine aminotransferase in women but not in men. The CSF/plasma FGF21 ratio was positively correlated with CSF FGF21 in both genders and with peripheral glucose, triglyceride, and gamma-glutamyl transferase levels in female Chinese patients. CONCLUSIONS: These results have important implications regarding the potential central actions of FGF21.

Cerebrospinal fluid oxytocin correlated with peripheral ALT and AST in Chinese female subjects.

OBJECTIVE: Oxytocin (OT) is primarily synthesized in the paraventricular nucleus of the hypothalamus and supraoptic nucleus of the hypothalamus in the central nervous system and exhibits a wide spectrum of central and peripheral activities. OT is involved in lipid metabolism and glucose homeostasis and plays a protective role against liver damage. METHODS: In this study, we investigated whether CSF OT levels correlates with peripheral glucose, lipid profiles, and/or liver enzymes in Chinese subjects. Sixty-nine subjects (n=36 males; n=33 females) who were recruited from Beijing Jishuitan Hospital participated in the study. Their levels of CSF OT and peripheral parameters were assayed by radioimmunoassay and continuous monitoring assay, respectively. RESULTS: There was no significant difference in CSF OT levels between males (53.09±6.88 nmol/mL) and females (52.34±6.87 nmol/mL), and no correlation found between CSF OT levels and peripheral glucose and lipid profiles. Significant negative correlation was observed between CSF OT levels and peripheral ALT and AST concentration in females but not in males. CONCLUSION: Our results support the physiological role of neuropeptides acting on brain sites to regulate liver enzymes, and shed new light on the brain-liver interaction.

[Biomechanical effect on adjacent vertebra after percutaneous kyphoplasty with cement leakage into disc: a finite element analysis of thoracolumbar osteoporotic vertebral compression fracture].

OBJECTIVE: To explore the biomechanical effects on adjacent vertebra of thoracolumbar osteoporotic vertebral compression fracture (OVCF) after percutaneous kyphoplasty (PKP) with cement leakage into the disc by using finite element analysis. METHODS: T10-L2 segment data were obtained from computed tomography (CT) scans of an elder female with single T12 OVCF undergoing a cement leakage into the T12-L1 disc after PKP. A three-dimensional finite element Model of thoracolumbar spine (T10-L2) was built in the Mimics and the ABAQUS software. The stress on annulus fiber, nucleus pulposus, endplate and facet joints under axial pressure (0.3, 1.0, 4.0 MPa) were analyzed. RESULTS: The 3D finite element after percutaneous kyphoplasty (PKP) with cement leakage into the disc may be strongly related with the changes of biomechanical effects on adjacent vertebra of thoracolumbar OVCF. Models of thoracolumbar OVCF before and after PVP with a cement leakage into the T12-L1 disc were successfully established. The stresses increased with a rising axial pressure in the model of cement leakage into the disc after PVP, the stress augmentation scope on adjacent end plates(T11 low plate & L1 top plate) and intervertebral disc (T11-12 & T12-L1) increased. The maximal Von Mises stress on adjacent vertebra (T11 & L1) increased while but the maximal Von Mises stress on end vertebra (T10 & L2) decreased. CONCLUSION: Postoperative adjacent vertebral fracture.

[Three-dimensional finite element model of thoracolumbar spine with osteoporotic vertebral compression fracture].

OBJECTIVE: To build a three-dimensional finite element model of thoracolumbar spine with osteoporotic vertebral compression fracture (OVCF) and analyze its biomechanical change. METHODS: The T10-L2 segment data were obtained from computed tomography (CT) scans of an elderly female with a single T12 OVCF. A three-dimensional finite element model of thoracolumbar spine was constructed with the MIMICS and ABAQUS software. The model was composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments. The basic stress analysis of T10-L2 motion segment was made for different material properties of bone, ligaments and facet joints contacting frictional property. The stress on the annulus fiber, nucleus pulposus, endplate and facet joints under axial pressure (0.3 MPa, 1.0 MPa, 4.0 MPa) were analyzed. RESULTS: A three-dimensional finite element model of human T12-L2 motion segment had 617468 elements. And the stress was higher in vertebral body than posterior structure. The distribution of pressure stresses in intervertebral disc was asymmetrical. The stress increased with a rising axial pressure. CONCLUSION: 3D finite element model of thoracolumbar OVCF and adjacent segments are successfully established. The results of stress analysis are both feasible and reliable.

Fusion protein of ATPase domain of Hsc70 with TRP2 acting as a tumor vaccine against B16 melanoma.

HSP70s are a family of ATP-dependent chaperones of relative molecular masses around 70kDa. Immunization of mice with HSP70 isolated from tumor tissues has been proved to elicit specific protective immunity against the original tumor. Recent researches have demonstrated that the ATPase domain of HSP70 and the tumor antigenic peptide that binds to Hsp70 were the crucial parts eliciting tumor-specific immunity. These findings suggested that a recombinant protein expressed in Escherichia coli, comprising a covalently fused fragment of tumor rejection antigen to ATPase domain of HSP70, could be used as a tumor vaccine. However, high-level expressions of heterologous recombinant proteins in E. coli often lead to the formation of inclusion bodies, resulting in defects in solubility and bioactivity. In the present work, we found an approach to resolve these problems, focusing on a refolding procedure via gel-filtration chromatography for denatured inclusion body proteins. Here, we expressed, purified and refolded a fusion protein comprising murine heat shock cognate protein 70 (Hsc70) N-terminal ATPase domain (Hsc70NTD) and a portion of TRP2 (aa153-417) as a model protein. The refolding effectivities were assessed according to their ATPase activities, the vaccine function was assessed according to immunization effect in inducing antigen-specific CTLs and to in vivo tumor protection. The results showed that the fusion protein refolded via gel-filtration chromatography exhibited ATPase activity, succeeded in eliciting antigen-specific CTL in vivo and delayed tumor growth on tumor-bearing mice.