Objective: To evaluate the role of the serum GrB and sFasl in the development of VMC and correlation with the serum myocardium enzyme. Methods: 40 children with VMC were selected. There were 30 healthy children as controls. By using the method of ELISA. the level of serum GrB and sFasL was assayed. Results:The levels of serum GrB and sFasL in patients with VMC were higher than those in the healthy group ( P 0. 05) .There was a positive correlation between the level of serum GrB,sFasL and myocardium enzyme. Conclusion: The higher level of serum GrB and sFasL may be important to the development of virus myocarditis in children.
ABSTRACT Articular cartilage (AC) is essential for body movement, but is highly susceptible to degenerative diseases and has poor self-repair capacity. To improve current subpar regenerative treatment, developmental mechanisms of AC should be clarified and, specifically, how postnatal multi-zone organization is acquired. Primary cilia are cell surface organelles crucial for mammalian tissue morphogenesis and while the importance of chondrocyte primary cilia is well appreciated their specific roles in postnatal AC morphogenesis remain unclear. To explore these mechanisms, we used a murine conditional loss-of-function approach ( Ift88-flox ) targeting joint-lineage progenitors ( Gdf5Cre ) and monitored postnatal knee AC development. Joint formation and growth up to juvenile stages were largely unaffected, however mature AC (aged 2 months) exhibited disorganized extracellular matrix, decreased aggrecan and collagen II due to reduced gene expression (not increased catabolism), and marked reduction of AC modulus by 30-50%. In addition, we discovered the surprising findings that tidemark patterning was severely disrupted and accompanied alterations in hedgehog signaling that were also dependent on regional load-bearing functions of AC. Interestingly, Prg4 expression was also increased in those loaded sites. Together, our data provide evidence that primary cilia orchestrate postnatal AC morphogenesis, dictating tidemark topography, zonal matrix composition and mechanical load responses.
Tendon experiences a variety of multiscale changes to its extracellular matrix during mechanical loading at the fascicle, fibre and fibril levels. For example, tensile loading of tendon increases its stiffness, with organization of collagen fibres, and increases cell strain in the direction of loading. Although applied macroscale strains correlate to cell and nuclear strains in uninjured tendon, the multiscale response during tendon healing remains unknown and may affect cell mechanosensing and response. Therefore, this study evaluated multiscale structure–function mechanisms in response to quasi-static tensile loading in uninjured and healing tendons. We found that tendon healing affected the macroscale mechanical and structural response to mechanical loading, evidenced by decreases in strain stiffening and collagen fibre realignment. At the micro- and nanoscales, healing resulted in increased collagen fibre disorganization, nuclear disorganization, decreased change in nuclear aspect ratio with loading, and decreased indentation modulus compared to uninjured tendons. Taken together, this work supports a new concept of nuclear strain transfer attenuation during tendon healing and identifies several multiscale properties that may contribute. Our work also provides benchmarks for the biomechanical microenvironments that tendon cells may experience following cell delivery therapies.
Our objective is to provide an in-depth review of the recent technical advances of atomic force microscopy (AFM)-based nanomechanical tests and their contribution to a better understanding and diagnosis of osteoarthritis (OA), as well as the repair of tissues undergoing degeneration during OA progression. We first summarize a range of technical approaches for AFM-based nanoindentation, including considerations in both experimental design and data analysis. We then provide a more detailed description of two recently developed modes of AFM-nanoindentation, a high-bandwidth nanorheometer system for studying poroviscoelasticity and an immunofluorescence-guided nanomechanical mapping technique for delineating the pericellular matrix (PCM) and territorial/interterritorial matrix (T/IT-ECM) of surrounding cells in connective tissues. Next, we summarize recent applications of these approaches to three aspects of joint-related healthcare and disease: cartilage aging and OA, developmental biology and OA pathogenesis in murine models, and nanomechanics of the meniscus. These studies were performed over a hierarchy of length scales, from the molecular, cellular to the whole tissue level. The advances described here have contributed greatly to advancing the fundamental knowledge base for improved understanding, detection, and treatment of OA.
Molecular engineering of biological tissues using synthetic mimics of native matrix molecules can modulate the mechanical properties of the cellular microenvironment through physical interactions with existing matrix molecules, and in turn, mediate the corresponding cell mechanobiology. In articular cartilage, the pericellular matrix (PCM) is the immediate microniche that regulates cell fate, signaling, and metabolism. The negatively charged osmo-environment, as endowed by PCM proteoglycans, is a key biophysical cue for cell mechanosensing. This study demonstrated that biomimetic proteoglycans (BPGs), which mimic the ultrastructure and polyanionic nature of native proteoglycans, can be used to molecularly engineer PCM micromechanics and cell mechanotransduction in cartilage. Upon infiltration into bovine cartilage explant, we showed that localization of BPGs in the PCM leads to increased PCM micromodulus and enhanced chondrocyte intracellular calcium signaling. Applying molecular force spectroscopy, we revealed that BPGs integrate with native PCM through augmenting the molecular adhesion of aggrecan, the major PCM proteoglycan, at the nanoscale. These interactions are enabled by the biomimetic "bottle-brush" ultrastructure of BPGs and facilitate the integration of BPGs within the PCM. Thus, this class of biomimetic molecules can be used for modulating molecular interactions of pericellular proteoglycans and harnessing cell mechanosensing. Because the PCM is a prevalent feature of various cell types, BPGs hold promising potential for improving regeneration and disease modification for not only cartilage-related healthcare but many other tissues and diseases.
Although it is recognized that pulmonary hysteresis can influence the effects of positive end-expiratory pressure (PEEP), the extent to which expansion of previously opened (vs. newly opening) peripheral airspaces contribute to increased lung volume is unknown.
This study elucidates the influences of adding covalent cross-linking on the nanomechanical viscoelasticity of ionically cross-linked polyelectrolyte networks.
