310 research outputs found

    Three-Scale Multiphysics Modeling of Transport Phenomena within Cortical Bone

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    Bone tissue can adapt its properties and geometry to its physical environment. This ability is a key point in the osteointegration of bone implants since it controls the tissue remodeling in the vicinity of the treated site. Since interstitial fluid and ionic transport taking place in the fluid compartments of bone plays a major role in the mechanotransduction of bone remodeling, this theoretical study presents a three-scale model of the multiphysical transport phenomena taking place within the vasculature porosity and the lacunocanalicular network of cortical bone. These two porosity levels exchange mass and ions through the permeable outer wall of the Haversian-Volkmann canals. Thus, coupled equations of electrochemohydraulic transport are derived from the nanoscale of the canaliculi toward the cortical tissue, considering the intermediate scale of the intraosteonal tissue. In particular, the Onsager reciprocity relations that govern the coupled transport are checked

    Finite Element Studies of Transient Wave Propagation

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    The National Bureau of Standards (NBS) has been working to develop a nondestructive test method for heterogenous solids using transient stress waves [1-5]. The method is referred to as the impact-echo method. The technique involves introducing a transient stress pulse into a test object by mechanical impact at a point and measuring the surface displacement caused by the arrival of reflections of the pulse from internal defects and external boundaries. Successful signal interpretation requires an understanding of the nature of transient stress wave propagation in solids containing defects. A primary focus of the NBS program is on using the finite element method to gain this understanding.</p

    Dihydrolipoic Acid Conjugated Carbon Dots Accelerate Human Insulin Fibrillation

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    Protein fibrillation is believed to play an important role in the pathology and development of several human diseases, such as Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. Carbon dots (CDs), as a new type of nanoparticle have recently been extensively studied for potential biological applications, but their effects on protein fibrillation remain unexplored. In reality, any application in biological systems will inevitably have “contact” between proteins and CDs. In this study, human insulin was selected as a model protein to study the effects of CDs on protein fibrillation, as proteins may share a common mechanism to form fibrils. Hydrophobic CDs were conjugated with dihydrolipoic acid (DHLA-CDs) to facilitate their water solubility. Characterizations from thioflavin T fluorescence, circular dichroism spectroscopy and atomic force microscopy demonstrate that the presence of DHLA-CDs results in a higher rate of human insulin fibrillation, accelerating the conformational changes of human insulin from α-helix to β-sheet. This promoting effect is likely associated with the locally increased concentration of human insulin adsorbed on the surface of DHLA-CDs

    The role of intrinsic pathway in apoptosis activation and progression in Peyronie’s disease

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    Peyronie’s disease (PD) is a connective tissue disorder where formation of fibrous plaques in tunica albuginea (TA) and erectile tissue can result in penile deformity, pain, and erectile dysfunction. Fibrosis, its major pathological manifestation, arises from fibroblast proliferation and accumulation of extracellular matrix; PD progresses with formation of plaques or even ectopic calcification having the appearance of scar tissue, which prevent TA expansion during erections. The mechanisms underpinning PD are unclear, and relatively little is known about the disease itself. To date corrective surgery is the sole effective treatment. A greater understanding of PD pathophysiology at the molecular level has the potential to help develop novel medical therapeutic approaches. The aim of this study was to investigate the activation of the apoptotic intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD and control patients were assessed for the expression of bax, bcl-2, caspase 9 and 3 using immunohistochemistry, and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplasic bone tissue, in fibroblasts and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplasic bone tissue. Apoptotic cell death occurs in stabilized PD plaques and is partly induced by the intrinsic mitochondrial pathway. The present findings can have clinical implications and may help devise improved treatment strategies. A therapeutic approach aimed at enhancing apoptosis-inducing molecules would at least help delay the progression of PD. Identification of target molecules for gene construct or biological or chemical reagent delivery to target sites could contribute to induce PD plaque stabilization
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