冠心病中医辨证分型与内皮损伤、炎症反应及血小板活化的相关性研究

[目的]通过观察冠心病各中医证型患者在血管假性血友病因子(vWF)、高敏C反应蛋白(hs-CRP)、P-选择素(CD62P)等方面的差异,研究冠心病中医证型与内皮损伤、炎症反应、血小板活化的关系.[方法]将冠心病患者186例分为心血瘀阻型、痰阻心脉型、心肾阴虚型、气阴两虚型及阳气虚衰型,另选正常对照组30例,检测各组血中vWF、hs-CRP、CD62P水平.[结果]冠心病各中医证型患者血中vWF水平均高于正常对照组(P<0.05或P<0.01),但各证型间比较差异无显著性意义(P>0.05);冠心病各中医证型CD62水平比较,阳气虚衰型显著高于心血瘀阻型、痰阻心脉型、心肾阴虚型及气阴两虚型(P<0.05或P<0.01);各中医证型中阳气虚衰型患者hs-CRP水平显著高于心血瘀阻型、痰阻心脉型、心肾阴虚型、气阴两虚(P<0.05或P<0.01);各中医证型中阳气虚衰型患者hs-CRP异常率最高(73.3%),经卡方检验.与心血瘀阻型、痰阻心脉型、心肾阴虚型、气阴两虚型比较有显著性差异(P<0.05或P<0.01).[结论]冠心病各中医证型内皮损伤比较差异无显著性意义,炎症反应及血小板活化与阳气虚衰证型关系最为密切.     

Polymeric Microbubbles for Ultrasonic Molecular Imaging and Targeted Therapeutics

Gas-filled microbubbles ultrasound agent have received wide attention, not only because they can improve ultrasound signals, but also they can be used as drug/gene carriers. Among all types of microbubbles fabricated by different membrane materials and core gases, polymer-shell microbubbles are highly promising. Polymeric microbubbles are more stable than other soft shell microbubbles in vivo. Under destructive ultrasound, polymer-stabilized microbubbles disintegrate and emit a strong non-linear signal, which enables ultrasound imaging with superior sensitivity. Except for ultrasound imaging, polymeric microbubbles could also be applied as drug/gene-delivery system. The thick polymeric shells allow loading a large amount of drugs. Meanwhile, site-specific targeting and controlled drug release in the area of interest can be realized through chemical and physical modification. In this review, we highlight some of the recent examples on polymeric microbubbles and their applications in ultrasound molecular imaging and drug delivery.     

Molecularly imprinted bioartificial membranes for the selective recognition of biological molecules. Part 2: release of components and thermal analysis

Molecularly imprinted membranes imprinted for a large-molecular-weight protein were realised using a blend of natural and synthetic polymers. Bioartificial membranes of synthetic (poly(ethylene-co-vinyl alcohol)–EVAL, Clarene^®) and biological (Dextran) polymers, molecularly imprinted with α-amylase as the template, were prepared and investigated. Dimethyl sulfoxide (DMSO) solutions of the α-amylase template, Clarene and Dextran were mixed under stirring in the desired proportions and dipped in DMSO (solvent)/water (non solvent) mixture, to obtain the phase separation. The release of Clarene, Dextran and α-amylase in the inversion baths was quantified by spectrophotometric methods and final composition of membranes was established. To study the interactions between the polymer components and between polymeric materials and the template, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were carried out. Results indicated that stable and continuous bioartificial membranes of Clarene and Dextran can be obtained, whereby calorimetric analysis suggested the presence of high interaction between α-amylase and the Clarene component.     

Large Deformation Mechanisms,Plasticity, and Failure of an Individual Collagen Fibril With Different Mineral Content

Mineralized collagen fibrils are composed of tropocollagen molecules and mineral crystals derived from hydroxyapatite to form a composite material that combines optimal properties of both constituents and exhibits incredible strength and toughness. Their complex hierarchical structure allows collagen fibrils to sustain large deformation without breaking. In this study, we report a mesoscale model of a single mineralized collagen fibril using a bottom‐up approach. By conserving the three‐dimensional structure and the entanglement of the molecules, we were able to construct finite‐size fibril models that allowed us to explore the deformation mechanisms which govern their mechanical behavior under large deformation. We investigated the tensile behavior of a single collagen fibril with various intrafibrillar mineral content and found that a mineralized collagen fibril can present up to five different deformation mechanisms to dissipate energy. These mechanisms include molecular uncoiling, molecular stretching, mineral/collagen sliding, molecular slippage, and crystal dissociation. By multiplying its sources of energy dissipation and deformation mechanisms, a collagen fibril can reach impressive strength and toughness. Adding mineral into the collagen fibril can increase its strength up to 10 times and its toughness up to 35 times. Combining crosslinks with mineral makes the fibril stiffer but more brittle. We also found that a mineralized fibril reaches its maximum toughness to density and strength to density ratios for a mineral density of around 30%. This result, in good agreement with experimental observations, attests that bone tissue is optimized mechanically to remain lightweight but maintain strength and toughness. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Propranolol Promotes Bone Formation and Limits Resorption Through Novel Mechanisms During Anabolic Parathyroid Hormone Treatment in Female C57BL/6J Mice

Although the nonselective β-blocker, propranolol, improves bone density with parathyroid hormone (PTH) treatment in mice, the mechanism of this effect is unclear. To address this, we used a combination of in vitro and in vivo approaches to address how propranolol influences bone remodeling in the context of PTH treatment. In female C57BL/6J mice, intermittent PTH and propranolol administration had complementary effects in the trabecular bone of the distal femur and fifth lumbar vertebra (L₅), with combination treatment achieving microarchitectural parameters beyond that of PTH alone. Combined treatment improved the serum bone formation marker, procollagen type 1 N propeptide (P1NP), but did not impact other histomorphometric parameters relating to osteoblast function at the L₅. In vitro, propranolol amplified the acute, PTH-induced, intracellular calcium signal in osteoblast-like cells. The most striking finding, however, was suppression of PTH-induced bone resorption. Despite this, PTH-induced receptor activator of nuclear factor κ-B ligand (RANKL) mRNA and protein levels were unaltered by propranolol, which led us to hypothesize that propranolol could act directly on osteoclasts. Using in situ methods, we found Adrb2 expression in osteoclasts in vivo, suggesting β-blockers may directly impact osteoclasts. Consistent with this, we found propranolol directly suppresses osteoclast differentiation in vitro. Taken together, this work suggests a strong anti-osteoclastic effect of nonselective β-blockers in vivo, indicating that combining propranolol with PTH could be beneficial to patients with extremely low bone density. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP-OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP-OA. Thirty-nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP-OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro–computed tomography and micro–finite-element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP-OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP-OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone-metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.     

石菖蒲冰片对神经细胞缺氧性损伤的保护作用

目的 探讨石菖蒲，冰片对缺氧损伤神经细胞的保护作用。方法 在缺氧培养条件下造成大鼠神经细胞损伤，测定空白对照组，模型对照组，石菖蒲挥发油组，冰片组，冰片＋石菖蒲挥发油（低，中，高配比）组神经元细胞数，神经细胞支配面积。结果 石菖蒲挥发油，冰片，冰片＋挥发油（低，中，高配比）给药组神经细胞支配面积和神经元细胞数高于空白对照组和模型对照组。结论 石菖蒲，冰片对缺氧诱导的大鼠神经细胞损伤具有保护作用。     

High levels of β‐catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self‐renewal makes them an excellent cell source for bone regeneration and repair. However, their bone‐regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of β‐catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P‐PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of β‐catenin in P‐PDLSCs than in H‐PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of β‐catenin suppresses the noncanonical Wnt/Ca²⁺ pathway, leading to increased proliferation but reduced osteogenic differentiation of P‐PDLSCs. Downregulation of the levels of β‐catenin by treatment with dickkopf‐1 (DKK‐1) leads to activation of the noncanonical Wnt/Ca²⁺ pathway, which, in turn, results in the promotion of osteogenic differentiation in P‐PDLSCs. Interestingly, β‐catenin can affect both the canonical Wnt/β‐catenin pathway and the noncanonical Wnt/Ca²⁺ pathway. Our data indicate that β‐catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments. © 2011 American Society for Bone and Mineral Research