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Purpose: To investigate the fracture-healing effect of boeravinone B in ovariectomy-induced (OVX) osteoporotic rats. Methods: Adult female Wistar rats (n = 30) were ovariectomized and after three months, the unilateral cross-tibial fractures were fixed with intramedullary nails. The rats were then randomly assigned to three groups of 10 rats each: normal control group, OVX group and 100 mg/kg body weight boeravinone B group. Boeravinone B was orally administered for a period of 5 weeks. The effect of boeravinone B on indices of bone formation and resorption was assessed. Levels of inflammatory cytokines including tumor necrosis factor- a (TNF-a) and interleukin-1ß (IL-1ß) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the expression levels of NF-κB p65, IκB-α and SIRT1 proteins. Results: There were significant increases in the activities of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP), and collagen type I fragment (CTX) level and serum osteocalcin (OC) of OVX group, when compared with normal control group (p < 0.05). However, treatment with boeravinone B significantly reduced the activities and levels of these parameters, relative to OVX group (p < 0.05). The levels of TNF-a and IL-1ß significantly increased in OVX group, relative normal control group, but were significantly lower following treatment with boeravinone B (p < 0.05). Bone mineral content (BMC) was not significantly altered in OVX and boeravinone B-treated groups, when compared with normal control group (p > 0.05). There was significant reduction in bone mineral density (BMD) of OVX group relative to normal control group (p < 0.05). However, treatment with boeravinone B significantly increased the BMD, when compared with OVX group (p < 0.05). After Week 5 of treatment, boeravinone B significantly enhanced bone remodeling and formation of callus. Treatment with boeravinone B significantly reduced the expression levels of NF-κB p65 and IκB-α proteins, and significantly upregulated the expression of SIRT-1 (p < 0.05). Conclusion: The results obtained in this study suggest that boeravinone B promotes the healing of fracture caused by osteoporosis via a mechanism involving NF-κB p65/IκB-α/SIRT-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Transforming growth factor β1 (TGF-β1) is known to be both anti-inflammatory and profibrotic. Cross-talk between TGF-β/Smad and Wnt/β-catenin pathways in epithelial-mesenchymal transition (EMT) suggests a specific role for β-catenin in profibrotic effects of TGFβ1. However, no such mechanistic role has been demonstrated for β-catenin in the anti-inflammatory effects of TGF-β1. In the present study, we explored the role of β-catenin in the profibrotic and anti-inflammatory effects of TGF-β1 by using a cytosolic, but not membrane, β-catenin knockdown chimera (F-TrCP-Ecad) and the β-catenin/CBP inhibitor ICG-001. TGF-β1 induced nuclear Smad3/βcatenin complex, but not β-catenin/LEF-1 complex or TOP-flash activity, during EMT of C1.1 (renal tubular epithelial) cells. F-TrCPEcad selectively degraded TGF-β1-induced cytoplasmic β-catenin and blocked EMT of C1.1 cells. Both F-TrCP-Ecad and ICG-001 blocked TGF-β1-induced Smad3/β-catenin and Smad reporter activity in C1.1 cells, suggesting that TGF-β1-induced EMT depends on β-catenin binding to Smad3, but not LEF-1 downstream of Smad3, through canonical Wnt. In contrast, in J774 macrophages, the β-catenin level was low and was not changed by interferon-c (IFN-β) or lipopolysaccharide (LPS) with or without TGF-β1. TGF-β1 inhibition of LPS-induced TNF-α and IFN-γ-stimulated inducible NO synthase (iNOS) expression was not affected by F-TrCP-Ecad, ICG-001 or by overexpression of wild-type β-catenin in J774 cells. Inhibition of β-catenin by either F-TrCP-Ecad or ICG-001 abolished LiCl-induced TOP-flash, but not TGF-β1-induced Smad reporter, activity in J774 cells. These results demonstrate for the first time that β-catenin is required as a co-factor of Smad in TGF-β1-induced EMT of C1.1 epithelial cells, but not in TGF-β1 inhibition of macrophage activation. Targeting β-catenin may dissociate the TGF-β1 profibrotic and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

The passive mega-subcontrolled structure proposed recently is a new form of structure associated with the design and construction of supertall buildings. However, a shortcoming still exists in its structural configuration. In this paper, a new configuration of the passive mega-subcontrolled frame is proposed. A more realistic analytical model of this structure subjected to random wind loads is presented, in which the substructures are treated as a multi-degree-of-freedom (MDOF) system and a nonwhite stochastic process in time and space is used. The dynamic equations and the response spectrum expressions, as well as the mean square response expressions, are derived on the basis of complex modal-analysis theory. A practical steel passive mega-subcontrolled frame is investigated; it is designed with reference to the conventional mega-subframe used in the Tokyo City Hall. The influence of the relative mass ratio and the relative stiffness ratio on the controlling effectiveness is investigated; and a proposed relative stiffness region, which is very useful in practical engineering design, is first presented. The corresponding computing results demonstrate that the structural configuration proposed here has extraordinary effectiveness in controlling displacement responses and acceleration responses, and the shortcoming that existed in the previously presented configuration can be overcome effectively. [ABSTRACT FROM AUTHOR]

Most of the existing trackers address the visual tracking problem by extracting an appearance template from the first frame, which is used to localize the target in the current frame. Unfortunately, they typically face the model degeneration challenge, which easily results in model drift and target loss. To address this issue, a novel Template Adjustment Siamese Network (TA-Siam) is proposed in this paper. The proposed framework TA-Siam consists of two simple subnetworks: The template adjustment subnetwork for feature extraction and the classification-regression subnetwork for bounding box prediction. The template adjustment module adaptively uses the feature of subsequent frames to adjust the current template. It makes the template adapt to the target appearance variation of long-term sequence and effectively overcomes model drift problem of Siamese networks. In order to reduce classification errors, the rhombus labels are proposed in our TA-Siam. For more efficient learning and faster convergence, our proposed tracker uses a more effective regression loss in the training process. Extensive experiments and comparisons with trackers are conducted on the challenging benchmarks including VOT2016, VOT2018, OTB50, OTB100, GOT-10K, and LaSOT. Our TA-Siam achieves state-of-the-art performance at the speed of 45 FPS. [ABSTRACT FROM AUTHOR]

An iron alloy coating with gradient transition was sprayed on F304 stainless steel substrate by plasma spraying method and with a gradient material obtained by the material performance simulation software, and the effect of gradient transition on the microstructure, hardness and wear resistance of the coating was analyzed by comparing with the non gradient transition coating. The results show that both the gradient coating and the non gradient coating have wavy layered structure and are formed by highly flattened deformed particles overlapping each other. Micro metallurgical bonding was observed between the coating particles, and oxides were observed between the coating and the substrate, between the flat particles and inside the flat layer. The coating microstructure includes austenite phase, ferrite phase and carbides. The surface hardness of the gradient coating and the non gradient transition coating are basically similar, but there are obvious steep drop steps between the section hardness of the non gradient coating and the substrate hardness, while the section hardness of the gradient coating and the substrate hardness change gently, and the section hardness of the gradient coating is slightly lower than that of the non gradient coating. The wear rate of gradient coating is similar to that of non gradient coating at 400 °C, but it is lower than that of non gradient transition coating at 350 °C. The reason for reducing hardness changes and improving wear resistance of the coating may be related to the improvement of the microstructure and plasticity of the coating by the gradient layer, but more research is needed. [ABSTRACT FROM AUTHOR]

The material performance simulation software JMatPro was used to simulate and calculate equilibrium phase structure and properties of a mixture formed by mixing different proportions of Norem02 alloy and F304 stainless steel. The results show that in the range of 500-1300 °C, equilibrium phases of the mixture include Austenite and Ferrite, and the carbides include M2(C,N), M6C, M7C3 and M23C6. As the content of F304 in the mixture increases, the phase transition temperature A1 of the mixture decreases, and A3 first decreases and then increases; in the equilibrium phase, the content of Austenite and Ferrite increases, and the content of carbide decreases until the carbides M7C3 and M6C gradually disappear. Density, coefficient of linear expansion, thermal conductivity, Young's modulus, Poisson's ratio and specific heat capacity of different mixture materials vary with temperature in a complex manner. Strength and hardness of the mixture formed when the content of F304 is 20 % is the highest. The finer the grain size of the mixture, the higher the strength and hardness of the material. Comparing standard physical property data of F304 stainless steel at room temperature with the simulation calculation results, it is found that the error is small, which verifies the accuracy of the simulation calculation results. [ABSTRACT FROM AUTHOR]

Aims: Luma is a recently discovered, evolutionarily conserved protein expressed in mammalian heart, which is associated with the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus and the cytoplasm and plays a critical role in mechanotransduction across the nuclear envelope. Mutations in several LINC components in both humans and mice result in various cardiomyopathies, implying they play essential, non-redundant roles. A single amino acid substitution of serine 358 to leucine (S358L) in Luma is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy. However, the role of Luma in heart has remained obscure. In addition, it also remains to be determined how the S358L mutation in Luma leads to cardiomyopathy. Methods And Results: To determine the role of Luma in the heart, we first determined the expression pattern of Luma in mouse heart. Luma was sporadically expressed in cardiomyocytes throughout the heart, but was highly and uniformly expressed in cardiac fibroblasts and vascular smooth muscle cells. We also generated germline null Luma mice and discovered that germline null mutants were viable and exhibited normal cardiac function. Luma null mice also responded normally to pressure overload induced by transverse aortic constriction. In addition, localization and expression of other LINC complex components in both cardiac myocytes and fibroblasts was unaffected by global loss of Luma. Furthermore, we also generated and characterized Luma S358L knock-in mice, which displayed normal cardiac function and morphology. Conclusion: Our data suggest that Luma is dispensable for murine cardiac development and function and that the Luma S358L mutation alone may not cause cardiomyopathy in mice. [ABSTRACT FROM AUTHOR]

The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin. However, previous studies have yet to identify which isoform is responsible. To elucidate this, we generated a series of nesprin 1 mutant mice. We showed that the actin-binding domains of nesprin 1 were dispensable, whereas nesprin 1α2, which lacks actin-binding domains, was crucial for postnatal viability, nuclear positioning, and skeletal muscle function. Furthermore, we revealed that kinesin 1 was displaced in fibers of nesprin 1α2-knockout mice, suggesting that this interaction may play an important role in positioning of myonuclei and functional skeletal muscle. [ABSTRACT FROM AUTHOR]

Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway. [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy (AC) is associated with mutations in genes encoding intercalated disc proteins and ultimately results in sudden cardiac death. A subset of patients with AC have the autosomal recessive cardiocutaneous disorder Naxos disease, which is caused by a 2-base pair deletion in the plakoglobin-encoding gene JUP that results in a truncated protein with reduced expression. In mice, cardiomyocyte-specific plakoglobin deficiency recapitulates many aspects of human AC, and overexpression of the truncated Naxos-associated plakoglobin also results in an AC-like phenotype; therefore, it is unclear whether Naxos disease results from loss or gain of function consequent to the plakoglobin mutation. Here, we generated 2 knockin mouse models in which endogenous Jup was engineered to express the Naxos-associated form of plakoglobin. In one model, Naxos plakoglobin bypassed the nonsense-mediated mRNA decay pathway, resulting in normal levels of the truncated plakoglobin. Moreover, restoration of Naxos plakoglobin to WT levels resulted in normal heart function. Together, these data indicate that a gain of function in the truncated form of the protein does not underlie the clinical phenotype of patients with Naxos disease and instead suggest that insufficiency of the truncated Naxos plakoglobin accounts for disease manifestation. Moreover, these results suggest that increasing levels of truncated or WT plakoglobin has potential as a therapeutic approach to Naxos disease. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXRs) are nuclear receptors that function as ligand-activated transcription factors regulating lipid metabolism and inflammation. Recent discoveries found LXRs could regulate tumor growth in a variety of cancer cell lines. In this study, we investigated the effect of LXR activation on melanoma cell proliferation and apoptosis both in vitro and in vivo. Treatment of B16F10 and A-375 melanoma cells with synthetic LXR agonist T0901317 significantly inhibited the proliferation of melanoma cells in vitro. Meanwhile, T0901317 induced the apoptosis of B16F10 melanoma cells in a dose-dependent manner. Furthermore, western blot assay showed that the pro-apoptotic effect of T0901317 on B16F10 melanoma cells was mediated through caspase-3 pathway. Oral administration of T0901317 inhibited the growth of B16F10 melanoma in C56BL/6 mice. Altogether, this study demonstrates the critical role of LXRs in the regulation of melanoma growth and presents the LXR agonist T0901317 as a potential anti-melanoma agent. [ABSTRACT FROM AUTHOR]

Nemaline myopathy (NM) is a congenital myopathy with an estimated incidence of 1:50,000 live births. It is caused by mutations in thin filament components, including nebulin, which accounts for about 50% of the cases. The identification of NM cases with nonsense mutations resulting in loss of the extreme C-terminal SH3 domain of nebulin suggests an important role of the nebulin SH3 domain, which is further supported by the recent demonstration of its role in IGF-1-induced sarcomeric actin filament formation through targeting of N-WASP to the Z-line. To provide further insights into the functional significance of the nebulin SH3 domain in the Z-disk and to understand the mechanisms by which truncations of nebulin lead to NM, we took two approaches: (1) an affinity-based proteomic screening to identify novel interaction partners of the nebulin SH3 domain; and (2) generation and characterization of a novel knockin mouse model with a premature stop codon in the nebulin gene, eliminating its C-terminal SH3 domain (NebDSH3 mouse). Surprisingly, detailed analyses of NebDSH3 mice revealed no structural or histological skeletal muscle abnormalities and no changes in gene expression or localization of interaction partners of the nebulin SH3 domain, including myopalladin, palladin, zyxin and N-WASP. Also, no significant effect on peak isometric stress production, passive tensile stress or Young's modulus was found. However, NebDSH3 muscle displayed a slightly altered force-frequency relationship and was significantly more susceptible to eccentric contraction-induced injury, suggesting that the nebulin SH3 domain protects against eccentric contraction-induced injury and possibly plays a role in finetuning the excitation-contraction coupling mechanism. [ABSTRACT FROM AUTHOR]

Nebulin (NEB) is a large, rod-like protein believed to dictate actin thin filament length in skeletal muscle. NEB gene defects are associated with congenital nemaline myopathy. The functional role of NEB was investigated in gastrocnemius muscles from neonatal wild-type (WT) and NEB knockout (NEB-KO) mice, whose thin filaments have uniformly shorter lengths compared with WT mice. Isometric stress production in NEB-KO skeletal muscle was reduced by 27% compared with WT skeletal muscle on postnatal day 1 and by 92% on postnatal day 7, consistent with functionally severe myopathy. NEB-KO muscle was also more susceptible to a decline in stress production during a bout of 10 cyclic isometric tetani. Length-tension properties in NEB-KO muscle were altered in a manner consistent with reduced thin filament length, with length-tension curves from NEB-KO muscle demonstrating a 7.4% narrower functional range and an optimal length reduced by 0.13 muscle lengths. Expression patterns of myosin heavy chain isoforms and total myosin content did not account for the functional differences between WT and NEB-KO muscle. These data indicate that NEB is essential for active stress production, maintenance of functional integrity during cyclic activation, and length-tension properties consistent with a role in specifying normal thin filament length. Continued analysis of NEB's functional properties will strengthen the understanding of force transmission and thin filament length regulation in skeletal muscle and may provide insights into the molecular processes that give rise to nemaline myopathy. [ABSTRACT FROM AUTHOR]

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice. [ABSTRACT FROM AUTHOR]

Heart performance relies on highly coordinated excitation-contraction (EC) coupling, and defects in this critical process may be exacerbated by additional genetic defects and/or environmental insults to cause eventual heart failure. Here we report a regulatory pathway consisting of the RNA binding protein RBFox2, a stress-induced microRNA miR-34a, and the essential EC coupler JPH2. In this pathway, initial cardiac defects diminish RBFox2 expression, which induces transcriptional repression of miR-34a, and elevated miR-34a targets Jph2 to impair EC coupling, which further manifests heart dysfunction, leading to progressive heart failure. The key contribution of miR-34a to this process is further established by administrating its mimic, which is sufficient to induce cardiac defects, and by using its antagomir to alleviate RBFox2 depletion-induced heart dysfunction. These findings elucidate a potential feed-forward mechanism to account for a critical transition to cardiac decompensation and suggest a potential therapeutic avenue against heart failure. [ABSTRACT FROM AUTHOR]

Background: Endothelial cells are known to contribute to kidney fibrosis via endothelial-mesenchymal transition (EndoMT). Matrix metalloproteinase 9 (MMP-9) is known to be profibrotic. However, whether MMP-9 contributes to kidney fibrosis via EndoMT is unknown. Methods: Primary mouse renal peritubular endothelial cells (MRPECs) were isolated and treated by recombinant human transforming growth factor beta 1 (rhTGF-β1) with or without MMP-9 inhibitor or by recombinant human MMP-9 (rhMMP- 9) alone. Kidney fibrosis was induced by unilateral ureteral obstruction (UUO) in MMP-9 knockout (KO) and wide-type (WT) control mice. The effects of MMP-9 on EndoMT of MRPECs and kidney fibrosis were examined. Results: We showed that MRPECs underwent EndoMT after rhTGF-β1 treatment or in UUO kidney as evidenced by decreased expression of endothelial markers, vascular endothelial cadherin (VE-cadherin) and CD31, and increased levels of mesenchymal markers, a-smooth muscle actin (a-SMA) and vimentin. The expression of fibrosis markers was also upregulated significantly after rhTGF-β1 treatment in MRPECs. The EndoMT and fibrosis markers were significantly less in rhTGF-β1-treated MMP-9 KO MRPECs, whereas MMP-9 alone was sufficient to induce EndoMT in MRPECs. UUO kidney ofMMP-9 KO mice showed significantly less interstitial fibrosis and EndoMT in MRPECs. Notch signaling shown by Notch intracellular domain (NICD) was increased, while Notch-1 was decreased in rhTGF-β1-treated MRPECs of MMP-9WT but notMMP-9 KO mice. Inhibition ofMMP-9 or Notch signaling prevented rhTGF-β1- or rhMMP-9-induced a-SMA and NICD upregulation in MRPECs. UUO kidney of MMP-9 KOmice had less staining of Notch signaling transcription factor Hey-1 in VE-cadherin-positive MRPECs than WT controls. Conclusions: Our results demonstrate that MMP-9-dependent Notch signaling plays an important role in kidney fibrosis through EndoMT ofMRPECs. [ABSTRACT FROM AUTHOR]

Background: Endothelial-mesenchymal transition (EndoMT) is a major source of myofibroblast formation in kidney fibrosis. Our previous study showed a profibrotic role for matrix metalloproteinase 9 (MMP-9) in kidney fibrosis via induction of epithelial-mesenchymal transition (EMT). Inhibition of MMP-9 activity reduced kidney fibrosis in murine unilateral ureteral obstruction. This study investigated whether MMP-9 also plays a role in EndoMT in human glomerular endothelial cells. Results: TGF-β1 (10 or 20 ng/ml) induced EndoMT in HKGECs as shown by morphological changes. In addition, VEcadherin and CD31 were significantly downregulated, whereas α-SMA, vimentin, and N-cadherin were upregulated. RT-PCR revealed that Snail, a known inducer of EMT, was upregulated. The MMP inhibitor GM6001 abrogated TGF-β1-induced EndoMT. Zymography indicated that MMP-9 was also upregulated in TGF-β1-treated HKGECs. Recombinant MMP-9 (2 μg/ml) induced EndoMT in HKGECs via Notch signaling, as evidenced by increased formation of the Notch intracellular domain (NICD) and decreased Notch 1. Inhibition of MMP-9 activity by its inhibitor showed a dose-dependent response in preventing TGF-β1-induced α-SMA and NICD in HKGECs, whereas inhibition of Notch signaling by γ-secretase inhibitor (GSI) blocked rMMP-9-induced EndoMT. Conclusions: Taken together, our results demonstrate that MMP-9 plays an important role in TGF-β1-induced EndoMT via upregulation of Notch signaling in HKGECs. [ABSTRACT FROM AUTHOR]

Emery-Dreifuss muscular dystrophy (EDMD) is a degenerative disease primarily affecting skeletal muscles in early childhood as well as cardiac muscle at later stages. EDMD is caused by a number of mutations in genes encoding proteins associated with the nuclear envelope (e.g., Emerin, Lamin A/C, and Nesprin). Recently, a novel protein, Lim-domain only 7 (lmo7) has been reported to play a role in the molecular pathogenesis of EDMD. Prior in vitro and in vivo studies suggested the intriguing possibility that Lmo7 plays a role in skeletal or cardiac muscle pathophysiology. To further understand the in vivo role of Lmo7 in striated muscles, we generated a novel Lmo7-null (lmo7-/-) mouse line. Using this mouse line, we examined skeletal and cardiac muscle physiology, as well as the role of Lmo7 in a model of muscular dystrophy and regeneration using the dystrophin-deficient mdx mouse model. Our results demonstrated that lmo7-/- mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. Cardiac function was also unaffected. Moreover, we found that ablation of lmo7 in mdx mice had no effect on the observed myopathy and muscular regeneration exhibited by mdx mice. Molecular analyses also showed no changes in dystrophin complex factors, MAPK pathway components, and Emerin levels in lmo7 knockout mice. Taken together, we conclude that Lmo7 is dispensable for skeletal muscle and cardiac physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

This paper proposes and demonstrates aptasensors for the detections of staphylococcus enterotoxin B (SEB) both in buffer and skim milk by using thiol-modified piezoresistive microcantilever. With attempts to optimize the design and fabrication processes of the microcantilever, the signal-to-noise rate of the aptasensor was greatly improved and an output voltage shift smaller than 1 \(\mu \) V was successfully obtained. By immobilizing thiol-modified target aptamers onto the nanogold-coated surface of the sensing cantilevers, different concentrations of SEB were detected with a wide detection range of 6-300 ng/mL in buffer, as well as in skim milk. All the experimental results indicate that the piezoresistive cantilever-based aptasensor has sufficient sensitivity to detect food contaminants and might provide an economical platform for on-site detections of different toxicants with the advantages of portability, high sensitivity, and rapid response. [ABSTRACT FROM AUTHOR]

Ultrasound examination is a non-invasive diagnostic technique that is used on patients with suspected or established renal disease. The purpose of this study was to determine the role of intrarenal Doppler ultrasonography in the assessment of the renal pathology of patients with chronic kidney disease (CKD), as shown by kidney biopsy. This retrospective analysis enrolled 992 consecutive patients with CKD who underwent intrarenal Doppler ultrasonography and a kidney biopsy at the Departments of Nephrology of three hospitals between January 2006 and December 2010. Doppler parameters, including the peak systolic velocity (PSV), end-diastolic velocity and resistive index (RI) of the interlobar arteries, were compared with the renal biopsy findings. The RI of the interlobar arteries was correlated with the estimated glomerular filtration rate and the histological damage scores, demonstrating the most evident correlation with the tubulointerstitial damage (TI) score among the three histological components. The PSV of the interlobar arteries increased as the CKD stage progressed and correlated with a number of the renal histological changes, including the glomerulosclerosis and TI scores. The RI and PSV of the interlobar artery are correlated with the histopathological pattern in CKD. Thus, the RI and PSV of the interlobar artery may be potential indicators for monitoring the progression of renal damage. [ABSTRACT FROM AUTHOR]

CD146, an endothelial biomarker, has been shown to be aberrantly upregulated during pathological angiogenesis and functions as a coreceptor for vascular endothelial growth factor receptor 2 (VEGFR-2) to promote disease progression. However, the regulatory mechanisms of CD146 expression during angiogenesis remain unclear. Using a microRNA screening approach, we identified a novel negative regulator of angiogenesis, microRNA 329 (miR-329), that directly targeted CD146 and inhibited CD146- mediated angiogenesis in vitro and in vivo. Endogenous miR-329 expression was downregulated by VEGF and tumor necrosis factor alpha (TNF-ɑ), resulting in the elevation of CD146 in endothelial cells. Upregulation of CD146 facilitated an endothelial response to VEGF-induced SRC kinase family (SKF)/p38 mitogen-activated protein kinase (MAPK)/NF-ɑB activation and consequently promoted endothelial cell migration and tube formation. Our animal experiments showed that treatment with miR-329 repressed excessive CD146 expression on blood vessels and significantly attenuated neovascularization in a mouse model of pathological angiogenesis. Our findings provide the first evidence that CD146 expression in angiogenesis is regulated by miR- 329 and suggest that miR-329 could present a potential therapeutic tool for the treatment of angiogenic diseases. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), among the most common malignancies worldwide, remains a major threat to public health, and there is an urgent need to identify novel biomarkers for diagnosis, prognosis and targets for anti-cancer treatment. In this study, two-dimensional polyacrylamide gel electrophoresis coupled with ESI-Q-TOF MS/MS analysis was used to identify differentially expressed proteins among the HCC tumour centre, tumour margin and nontumourous liver tissues. In total, 52 spots with significant alteration were positively identified by MS/MS analysis. Altered expression of representative proteins, including CIB1, was validated by Western blotting. Immunostaining suggested an increase tendency of CIB1 expression from nontumourous liver tissue to tumour centre. Knockdown of CIB1 expression by RNA interference led to the significant suppression of the cell growth in hepatoma HepG2 cells. These data suggest that CIB1 may be used as a novel prognostic factor and possibly an attractive therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

E-Cadherin/β-catenin complex plays an important role in maintaining epithelial integrity and disrupting this complex affect not only the adhesive repertoire of a cell, but also the Wnt-signaling pathway. Aberrant expression of the complex is associated with a wide variety of human malignancies and disorders of fibrosis resulting from epithelial-mesenchymal transition. These associations provide insights into the complexity that is likely responsible for the fibrosis/tumor suppressive action of E-cadherin/β-catenin. [ABSTRACT FROM AUTHOR]