Ubiquinone-10 Protects Neurons from Virus-Induced Degeneration

Abstract: Cultured neurons from rat dorsal root ganglia and cerebral cortex were infected with Sendai virus, which gives a productive replication with lysis of most neurons, and with the RW strain of mumps virus, which undergoes defective replication causing degeneration of only 30–40% of the neurons within 5 days after initial infection. In Sendai virus-infected cells the amount of polyisoprenoid lipids was enhanced. In mumps virus-infected cultures there were transient reductions in the contents of cholesterol, dolichol, and ubiquinone-9 in the cultures, whereas the reduction in the ubiquinone-10 level was progressive, reaching 20% of its original value 21 days after infection. Treatment of mumps virus-infected cultures with ubiquinone-10 protected the neurons from degeneration, whereas no effects were observed on exposure to ubiquinone-9. Linolenic acid (18:3) and arachidonic acid (20:4), but not myristic acid (14:0) and palmitic acid (16:0), also had significant neuroprotective effects.     

Metformin Protects Skeletal Muscle from Cardiotoxin Induced Degeneration

The skeletal muscle tissue has a remarkable capacity to regenerate upon injury. Recent studies have suggested that this regenerative process is improved when AMPK is activated. In the muscle of young and old mice a low calorie diet, which activates AMPK, markedly enhances muscle regeneration. Remarkably, intraperitoneal injection of AICAR, an AMPK agonist, improves the structural integrity of muscles of dystrophin-deficient mdx mice. Building on these observations we asked whether metformin, a powerful anti-hyperglycemic drug, which indirectly activates AMPK, affects the response of skeletal muscle to damage. In our conditions, metformin treatment did not significantly influence muscle regeneration. On the other hand we observed that the muscles of metformin treated mice are more resilient to cardiotoxin injury displaying lesser muscle damage. Accordingly myotubes, originated in vitro from differentiated C2C12 myoblast cell line, become more resistant to cardiotoxin damage after pre-incubation with metformin. Our results indicate that metformin limits cardiotoxin damage by protecting myotubes from necrosis. Although the details of the molecular mechanisms underlying the protective effect remain to be elucidated, we report a correlation between the ability of metformin to promote resistance to damage and its capacity to counteract the increment of intracellular calcium levels induced by cardiotoxin treatment. Since increased cytoplasmic calcium concentrations characterize additional muscle pathological conditions, including dystrophies, metformin treatment could prove a valuable strategy to ameliorate the conditions of patients affected by dystrophies.     

Dietary Supplement Enriched in Antioxidants and Omega-3 Protects from Progressive Light-Induced Retinal Degeneration

In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration.     

Systemic Gene Delivery Protects the Photoreceptors in the Retinal Degeneration Slow Mouse

The retinal degeneration slow (rds/rds) mouse was used to test photoreceptor protection by systemic gene delivery of non-erythropoietic forms of erythropoietin (EPO). Two Epo mutants were generated and packaged into recombinant adeno-associated virus (rAAV) serotype 2/5, controls included rAAV2/5.Epo and rAAV2/5.enhanced green fluorescent protein (eGFP). Mice were injected in the quadriceps at postnatal day seven and analyses were performed at postnatal day 90. Hematocrit, serum EPO levels, and outer nuclear layer (ONL) thickness were quantified. Hematocrit and serum EPO levels in rAAV2/5.eGFP, rAAV2/5.Epo, and rAAV2/5.EpoR103E treated mice were: 46%, 8 mU/ml; 63%, 117 mU/ml; and 52%, 332 mU/ml, respectively. The ONL from rds/rds mice treated with the Epo vectors were approximately twice as thick as the negative controls. This demonstrates that the photoreceptors can be protected without performing an intraocular injection and without increasing the hematocrit to unsafe levels. Intramuscular delivery of rAAV.EpoR103E is an attractive treatment for retinal degenerative diseases.     

慢性睡眠剥夺对颞下颌关节微结构的影响

目的:研究慢性睡眠障碍对大鼠颞下颌关节微结构的影响。方法:采用改良多平台法(MMPM)建立睡眠剥夺模型,将90只Wistar大鼠随机分为3组(n=30),分别为小平台组、网格组和对照组。小平台组和网格组大鼠接受每天18 h的睡眠剥夺和6 h间歇期(10:00—16:00),间歇期大鼠正常笼养。实验第7、14和21天时分别行动物行为学观察、旷场试验和动物血浆检测,并通过HE染色和扫描电镜观察颞下颌关节微结构的变化。结果:与对照组和网格组相比,小平台组大鼠血清促肾上腺激素(ACTH)和皮质醇(CORT)水平均增高(P<0.05),髁突软骨HE染色显示软骨细胞层次及厚度改变;扫描电镜结果显示关节盘表面纤维排列松散。结论:慢性睡眠障碍可能导致颞下颌关节微结构发生病理性改变。     

Erratum to: Systemic Gene Delivery Protects the Photoreceptors in the Retinal Degeneration Slow Mouse

Neurochemical Research -     

中国全新世人群颞下颌关节尺寸的时代变化

本文通过对中国北方地区新石器时代(54例)、青铜铁器时代(189例) 和近代(92例) 成年男性颞下颌关节的多项测量项目的对比、分析, 对中国全新世人群颞下颌关节测量性状的变异问题进行了研究。结果显示近7000年来颞下颌关节的不同部位在全新世不同阶段有不同的变化特点。髁突、冠突在全新世厚度变薄, 髁突的变薄主要在新石器-青铜铁器时代, 冠突的变薄主要在青铜铁器-近代。髁突面积在全新世也在缩小, 在新石器-青铜铁器时代缩小的幅度更大。髁突顶缘弧度的变平、下颌窝的变浅主要发生在新石器-青铜铁器时代。髁突面积/下颌窝面积, 其变化主要发生在青铜铁器时代。这些变化可能与生活环境、食物结构改变、下颌骨与头骨不同的演化速率等有关。     

Development of Synovial Membrane in the Temporomandibular Joint of the Human Fetus

The development of the synovial membrane was analyzed in serial sections of 21 temporomandibular joints of human fetuses at 9 to 13 weeks of gestation. Sections of two fetuses at 12 weeks of development were used to perform immunohistochemical expression of the markers CD68 and Hsp27 on the synovial lining. Macrophage-like type A and fibroblast-like type B cells, which express CD68 and Hsp27, respectively, were observed at the twelfth week of development. Our results suggest that the development of the synovial membrane is related to the vascularization of the joint and the formation of the articular cavities.Key words: Synovial membrane, immunohistochemistry, temporomandibular joint, fetus     

Elevated Shear Stress Protects Escherichia coli Cells Adhering to Surfaces via Catch Bonds from Detachment by Soluble Inhibitors

Soluble inhibitors find widespread applications as therapeutic drugs to reduce the ability of eukaryotic cells, bacteria, or viruses to adhere to surfaces and host tissues. Mechanical forces resulting from fluid flow are often present under in vivo conditions, and it is commonly presumed that fluid flow will further add to the inhibitive effect seen under static conditions. In striking contrast, we discover that when surface adhesion is mediated by catch bonds, whose bond life increases with increased applied force, shear stress may dramatically increase the ability of bacteria to withstand detachment by soluble competitive inhibitors. This shear stress-induced protection against inhibitor-mediated detachment is shown here for the fimbrial FimH-mannose-mediated surface adhesion of Escherichia coli. Shear stress-enhanced reduction of bacterial detachment has major physiological and therapeutic implications and needs to be considered when developing and screening drugs.     

The O-glycomap of Lubricin,a Novel Mucin Responsible for Joint Lubrication,Identified by Site-specific Glycopeptide Analysis

The lubricative, heavily glycosylated mucin-like synovial glycoprotein lubricin has previously been observed to contain glycosylation changes related to rheumatoid and osteoarthritis. Thus, a site-specific investigation of the glycosylation of lubricin was undertaken, in order to further understand the pathological mechanisms involved in these diseases. Lubricin contains an serine/threonine/proline (STP)-rich domain composed of imperfect tandem repeats (EPAPTTPK), the target for O-glycosylation. In this study, using a liquid chromatography–tandem mass spectrometry approach, employing both collision-induced and electron-transfer dissociation fragmentation methods, we identified 185 O-glycopeptides within the STP-rich domain of human synovial lubricin. This showed that adjacent threonine residues within the central STP-rich region could be simultaneously and/or individually glycosylated. In addition to core 1 structures responsible for biolubrication, core 2 O-glycopeptides were also identified, indicating that lubricin glycosylation may have other roles. Investigation of the expression of polypeptide N-acetylgalactosaminyltransferase genes was carried out using cultured primary fibroblast-like synoviocytes, a cell type that expresses lubricin in vivo. This analysis showed high mRNA expression levels of the less understood polypeptide N-acetylgalactosaminyltransferase 15 and 5 in addition to the ubiquitously expressed polypeptide N-acetylgalactosaminyltransferase 1 and 2 genes. This suggests that there is a unique combination of transferase genes important for the O-glycosylation of lubricin. The site-specific glycopeptide analysis covered 82% of the protein sequence and showed that lubricin glycosylation displays both micro- and macroheterogeneity. The density of glycosylation was shown to be high: 168 sites of O-glycosylation, predominately sialylated, were identified. These glycosylation sites were focused in the central STP-rich region, giving the domain a negative charge. The more positively charged lysine and arginine residues in the N and C termini suggest that synovial lubricin exists as an amphoteric molecule. The identification of these unique properties of lubricin may provide insight into the important low-friction lubricating functions of lubricin during natural joint movement.Human diarthrodial joints are surrounded by synovial fluid (SF),¹ a dense extracellular matrix fluid composed of proteins, glycoproteins, hyaluronic acid, proteoglycans, and phospholipids (1). During movement, the cartilage surfaces of the articulating joints slide over each other with an extremely low coefficient of friction that ranges from 0.0005 to 0.04 (2) and handle pressures up to ∼200 atm (3). In a healthy state, the joint surface and SF constitute a system of reduced friction that results in lifelong lubrication and wear resistance, primarily due to biolubricating molecules such as hyaluronic acid and lubricin (4). Human synovial lubricin is encoded by the proteoglycan 4 (Prg4) gene (5, 6) and is synthesized by fibroblast-like synoviocytes (FLSs) and superficial zone chondrocytes. Its 1404-amino-acid sequence contains a central mucin-like domain consisting of 59 imperfectly repeated sequences of EPAPTTPK. The O-glycosylation (in particular core 1 and sialylated core 1) of lubricin is suggested to be responsible for its lubricating properties (7), as the removal of these residues results in the loss of boundary lubrication. The molecule has also been suggested to play a key role in protecting the cartilage surface from excessive adsorption of proteins and cells (8).Arthritis results in the loss of this joint surface, leading to severe pain and a restricted range of motion. The two most common arthritic diseases, osteoarthritis (OA) and rheumatoid arthritis (RA), have different mechanisms of degradation. RA is an autoimmune systemic high inflammatory disease that increases the friction between articulating cartilage surfaces, resulting in degradation of the joint (9), whereas OA is a result of mechanical stress (10). Degeneration of the cartilage can be detected from proteoglycan fragments in the SF (11, 12). Because of the limited efficacy of available treatments, particularly for OA, understanding the biological factors related to arthritis is essential.The joints of arthritis patients, both RA and OA, have shown a down-regulation of expression and changes in glycosylation of lubricin (13). Studies using OA animal models suggest that there is a relationship between pathogenesis and the down-regulation of lubricin (9, 14, 15). This decrease in lubricin expression exacerbates the disease by accelerating the joint destruction, suggesting that certain characteristics of lubricin may be indicators of disease progression in RA and OA. Given the critical nature of lubricin glycosylation, we initiated a site-specific glycopeptide characterization of the lubricin mucin-like domain using liquid chromatography–tandem mass spectrometry with both collision-induced and electron-transfer dissociation fragmentation methods (LC-CID/ETD-MS²) after tryptic digestion of both intact and partly de-glycosylated lubricin.Collision-induced dissociation–tandem mass spectrometry (CID-MSⁿ) of O-linked (and N-linked) glycopeptides is capable of generating sequence information both for the attached glycan (in MS²) and for the de-glycosylated peptide (in MS³), but it lacks the site-specific information of the modified amino acids (16). This is due to extensive glycosidic bond cleavage of the precursor ion in MS² producing B/C and Y/Z ions (Domon and Costello carbohydrate fragmentation nomenclature (17)). In addition, the identification of the modified amino acids is even more difficult for peptides containing several Ser/Thr residues because of the lack of a consensus sequence for mucin-type O-glycosylation. Electron-capture dissociation and ETD are fragmentation techniques used for the site-specific characterization of protein post-translational modifications including phosphorylation (18) and glycosylation (19). Both techniques induce cleavage of the N-Cα bonds of the peptide backbone, producing c- and z-type fragment ions, while leaving the post-translational modification unaffected.In order to understand the biosynthesis of O-linked glycoproteins, one needs to link site localization of glycosylation to the expression of enzymes responsible for GalNAc-type (or mucin-type) O-glycosylation. This is necessary because the prediction of the site of GalNAc-type O-glycosylation is difficult. One reason for this is the large, redundant UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferase (ppGalNAc T) gene family containing 20 gene-encoded isoenzymes, all possessing unique and/or overlapping substrate specificities (20, 21). These ppGalNAc Ts transfer GalNAc from the sugar nucleotide donor UDP-GalNAc to the hydroxyl groups of Ser and Thr residues in the proteins traversing the Golgi/endoplasmic reticulum. Altered protein O-glycosylation, suggested to be due to changes in the expression of distinct ppGalNAc Ts, has been reported in various disease states, including ulcerative colitis and cancer (21, 22). Thus, the connection of site-specific O-glycosylation with the responsible ppGalNAc Ts is important for understanding the functions of lubricin, as site-specific O-glycosylation has been shown to regulate the functions of proteins (23, 24) and may be involved in the pathological transformation of the joint in arthritis diseases.Although the type of glycosylation present on lubricin has been investigated previously, the site-specific glycopeptide characterization, including the analysis of the glycan types at these locations, was investigated for the first time in this study. In order to understand the nature of glycoproteins, it is essential to not only define the protein component or the glycan characteristics, but also understand how these two essential components interact. The macro- (different site occupation) and micro-heterogeneity (different glycan structure at each site) provided a heterogeneous mixture of lubricin O-linked glycopeptides that might help to explain the extraordinary properties of lubricin and how it can function as a lubricating agent in a demanding environment.     

Inhibition of Fibrous Adhesion Formation in the Temporomandibular Joint of Tenascin-C Knockout Mice

Tenascin-C (TNC) is a large hexameric extracellular matrix glycoprotein that is expressed in developing organs and tumors. It has been reported that TNC is expressed in inflamed synovial membranes and deformed discs of temporomandibular joint (TMJ) disorder. However, the role of TNC in TMJ is not fully known. In this study, the role of TNC in fibrous adhesion formation of TMJ was examined using TNC knockout (TNCKO) mice. Hypermobility was produced by excessive mouth opening method on the TMJ of both wild-type (WT) and TNCKO mice. TMJ wound healing was compared histologically, and the expression of TNC, fibronectin (FN), and α-smooth muscle actin (α-SMA) in the wounded TMJ was examined by immunohistochemical and immunoblot analyses. Based on histologic analysis, fibrous adhesions were observed in the TMJ of both TNCKO and wild-type (WT) mice after excessive mouth opening. However, fibrous adhesion formation in TNCKO mice occurred later than in WT mice. TNC was expressed in the wounded TMJ disc and mandibular fossa. Although FN and α-SMA expression in the TMJ of TNCKO and WT mice was up-regulated after excessive mouth opening, FN and α-SMA protein levels were higher in WT mice at the same time points. In the wounded TMJ, TNC appears to enhance the expression of FN and α-SMA, and a lack of TNC may reduce fibrous adhesion formation in the TMJ. TNC plays an important role in TMJ wound healing, especially for wounds generated by mechanical stress.Key words: Temporomandibular joint, excessive mouth opening, fibrous adhesion, tenascin-C, fibronectin, α-smooth muscle actin     

The Biomechanical Effects of Sagittal Split Ramus Osteotomy on Temporomandibular Joint

Abstract

The aim of this study was to evaluate the stress distributions and deformations of the temporomandibular joint (TMJ) during different periods before and after sagittal split ramus osteotomy (SSRO). A three-dimensional finite element model of the mandible and TMJ was established, based on the preoperative CT of a patient with mandibular prognathism. Numerical SSRO was performed and the models of three postoperative periods were established. Contact elements were used to simulate the interaction between the articular discs and the articular cartilages. Nonlinear cable elements were used to simulate the disc attachments and the ligaments. Muscle forces and boundary conditions corresponding to the central occlusion were applied on all the models. The results showed that the stress distributions of the patient’s TMJs were not the same as those of asymptomatic subjects. The stress distributions and deformations of the disc, condylar and temporal cartilage were changed at different periods after SSRO. The biomechanical parameters of TMJ were improved after SSRO. And the postoperative results showed that appropriate functional training could help to avoid TMJ diseases. Therefore SSRO could improve the stress distributions of the TMJ and relieve the symptoms of temporomandibular disorder (TMD).     

BMPRIA Mediated Signaling Is Essential for Temporomandibular Joint Development in Mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development.     

Gap Arthroplasty versus Interpositional Arthroplasty for Temporomandibular Joint Ankylosis: A Meta-Analysis

Gap arthroplasty (GA) and interpositional arthroplasty (IA) are widely used for the treatment of temporomandibular joint ankylosis (TMJA). However, controversy remains as to whether IA is superior to GA. PubMed, EMBASE, the Cochrane Library, the Web of science and the China National Knowledge Infrastructure were searched for literature regarding these procedures (published from 1946 to July 28, 2014). A study was included in this analysis if it was: (1) a randomized controlled trial or non-randomized observational cohort study; (2) comparing the clinical outcomes between GA and IA with respect to the maximal incisal opening (MIO) and reankylosis; (3) with a follow-up period of at least 12 months. The methodological quality of the included studies was evaluated according to the Newcastle-Ottawa Scale Eight non-randomized observational cohort studies with 272 patients were included. All the statistical analyses were performed using the RevMan 5.3 and Stat 12. The pooled analysis showed no significant difference in the incidence of reankylosis between the IA group (13/120) and the GA group (29/163) (RR= 0.67, 95% CI=0.38 to 1.16; Z=1.43, p=0.15). The IA group showed a significantly larger MIO than the GA group (MD=1.96, 95% CI=0.21 to 3.72, Z=2.19, p=0.03, I²=0%). In conclusion, patients with TMJA could benefit more from IA than GA, with a larger MIO and a similar incidence of reankylosis. IA shows to be an adequate option in the treatment of TMJA based on the results of maximal incisal opening.     

关节灌洗术联合透明质酸钠注射治疗颞下颌关节骨关节炎的疗效观察

目的:评价关节腔灌洗联合透明质酸钠注射治疗颞下颌关节骨关节炎(TMJOA)的疗效及安全性。方法:选取我院2014年5月-2015年5月收治颞下颌关节骨关节炎患者68例作为研究对象,根据入院时间先后顺序按照随机数字表法随机分为实验组和对照组各34例。所有患者在颞颌关节区域局麻下建立关节上腔的双通道灌洗系统,实验组用生理盐水反复冲洗关节腔后注射透明质酸钠,对照组只进行关节腔灌洗术,术后随访对比两组治疗前、治疗后4周、6个月时患者非辅助最大开口度、侧向运动幅度、咀嚼时疼痛感;同时采用酶联免疫吸附法(ELISA)测定两组治疗前、治疗后4周血清中白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平并进行比较。结果:实验组患者治疗后4周、治疗后6个月时颞下颌关节最大张口度和侧向活动距离明显增大,而咀嚼时疼痛感明显减轻,且优于同期对照组,差异具有统计学意义(P0.05);实验组患者治疗后4周时血清IL-6、TNF-α水平较术前及同时期对照组均明显降低,差异具有统计学意义(P0.05)。结论:关节灌洗术联合透明质酸钠注射是治疗颞下颌关节骨关节炎的简单、安全有效治疗方法,治疗效果明显优于单纯关节腔灌洗,值得临床推广应用。     

How Synchronization Protects from Noise

The functional role of synchronization has attracted much interest and debate: in particular, synchronization may allow distant sites in the brain to communicate and cooperate with each other, and therefore may play a role in temporal binding, in attention or in sensory-motor integration mechanisms. In this article, we study another role for synchronization: the so-called “collective enhancement of precision”. We argue, in a full nonlinear dynamical context, that synchronization may help protect interconnected neurons from the influence of random perturbations—intrinsic neuronal noise—which affect all neurons in the nervous system. More precisely, our main contribution is a mathematical proof that, under specific, quantified conditions, the impact of noise on individual interconnected systems and on their spatial mean can essentially be cancelled through synchronization. This property then allows reliable computations to be carried out even in the presence of significant noise (as experimentally found e.g., in retinal ganglion cells in primates). This in turn is key to obtaining meaningful downstream signals, whether in terms of precisely-timed interaction (temporal coding), population coding, or frequency coding. Similar concepts may be applicable to questions of noise and variability in systems biology.     

Klotho Protects Dopaminergic Neuron Oxidant-Induced Degeneration by Modulating ASK1 and p38 MAPK Signaling Pathways

Klotho transgenic mice exhibit resistance to oxidative stress as measured by their urinal levels of 8-hydroxy-2-deoxyguanosine, albeit this anti-oxidant defense mechanism has not been locally investigated in the brain. Here, we tested the hypothesis that the reactive oxygen species (ROS)-sensitive apoptosis signal-regulating kinase 1 (ASK1)/p38 MAPK pathway regulates stress levels in the brain of these mice and showed that: 1) the ratio of free ASK1 to thioredoxin (Trx)-bound ASK1 is relatively lower in the transgenic brain whereas the reverse is true for the Klotho knockout mice; 2) the reduced p38 activation level in the transgene corresponds to higher level of ASK1-bound Trx, while the KO mice showed elevated p38 activation and lower level of–bound Trx; and 3) that 14-3-3ζ is hyper phosphorylated (Ser-58) in the transgene which correlated with increased monomer forms. In addition, we evaluated the in vivo robustness of the protection by challenging the brains of Klotho transgenic mice with a neurotoxin, MPTP and analyzed for residual neuron numbers and integrity in the substantia nigra pars compacta. Our results show that Klotho overexpression significantly protects dopaminergic neurons against oxidative damage, partly by modulating p38 MAPK activation level. Our data highlight the importance of ASK1/p38 MAPK pathway in the brain and identify Klotho as a possible anti-oxidant effector.     

口腔内入路行髁突高位骨折复位固定的临床效果

目的：探讨采用口腔内入路手术复位固定方法治疗下颌骨髁突颈骨折患者的临床效果。方法：将我院收治的20例下颌骨髁突颈骨折患者均使用口腔内入路手术复位固定方法治疗,将患者的骨折片与升支后缘骨块进行手术复位固定,并于原手术切口行回植,重建患者的下颌关节。结果：治疗后咬合关系异常者1例,开口范围限制者0例,关节疼痛者1例,均少于治疗前均为20例;治疗后关节间隙缩小者1例,髁突骨折块形状异常者1例,均少于治疗前均为20例。治疗后髁突稳定者19例,多于治疗前的1例。结论：髁突骨折治疗手术各有优缺点,采用口腔内入路手术复位固定方法治疗髁突高位骨折患者,虽然手术操作难度大,但能较好地克服了术后患者外部皮肤瘢痕明显的问题,有利于保护患者面部神经,提高患者治疗质量水平,值得临床上推广与进一步研究。