Osteochondral repair remains a challenge in clinical practice nowadays despite extensive advances in tissue engineering. The insufficient recruitment of endogenous cells in the early stage and ...incomplete cell differentiation in the later stage constitute the major difficulty of osteochondral repair. Here, a novel all-silk-derived multifunctional biomaterial platform for osteochondral engineering is reported. The bilayer methacrylated silk fibroin (SilMA) hydrogel was fabricated through stratified photocuring as the basic provisional matrix for tissue regeneration. Platelet-rich plasma (PRP) incorporation promoted the migration and pre-differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the early stage of implantation. The long-term regulation of BMSCs chondrogenesis and osteogenesis was realized by the stratified anchoring of the silk fibroin (SF) microspheres respectively loaded with Kartogenin (KGN) and berberine (BBR) in the hydrogel. The composite hydrogels were further demonstrated to promote BMSCs chondrogenic and osteogenic differentiation under an inflammatory microenvironment and to achieve satisfying cartilage and subchondral bone regeneration with great biocompatibility after 8 weeks of implantation. Since all the components used are readily available and biocompatible and can be efficiently integrated via a simple process, this composite hydrogel scaffold has tremendous potential for clinical use in osteochondral regeneration.
Overview of the integral bilayer SilMA hydrogel scaffold combined with PRP and the SF-KGN and SF-BBR microspheres in osteochondral repair. Display omitted
Many motion studies have shown that the inner bearing of bipolar prostheses moves less than expected under non-weight-bearing and static weight-bearing positions, which are not routine functional ...movements performed postoperatively. The aim of this study was to investigate the behaviours of bipolar prostheses during normal gait and simulative squatting.
Thirty-one femoral neck fracture patients were enrolled, and fluoroscopy examinations of walking on a treadmill, simulative squatting, and non-weight-bearing abduction-adduction and flexion-extension motions were performed at an average of 40 months postoperatively. The rate of acetabular cartilage degeneration was calculated. The ranges of motion of the outer bearing and inner bearing were determined, and the O/I ratios were calculated. Clinical efficacy was assessed by HHS and EQ-5D score.
The inner bearing moved more than the outer bearing did, with an O/I ratio of 0.81, during the normal gait examination, while the motion of the outer bearing was obviously dominant during the simulative squatting and non-weight-bearing abduction-adduction and flexion-extension examinations. The mean acetabular cartilage degeneration rate was 0.82 ± 0.54 mm/year at the follow-up. In subgroup analyses, the motion of the outer bearing decreased to some extent with the increase in acetabular wear, and the corresponding O/I ratios among the groups showed a trend of decreasing first and then increasing. The HHS and EQ-5D scores of the patients with osteolysis and femoral stem loosening were much worse than those with fixed implants.
Bipolar prostheses do function as originally intended during gait, but movement primarily occurs at the outer bearing during other examinations. The motion patterns of bipolar prostheses change with the increase in acetabular wear.
Circular RNAs (circRNAs) have emerged as important roles in various inflammatory processes of rheumatic diseases. However, their expression profiles and influences in the pathogenesis of ankylosing ...spondylitis (AS) remain unclear. In this study, we revealed the differential expression profiles of circRNAs in peripheral blood mononuclear cells (PBMCs) in AS by circRNA sequencing. We screened the differentially expressed circRNAs in AS and verified that hsa_circ_0000652 was upregulated and had potential to be a biomarker of progression. Functionally, hsa_circ_0000652 promoted proliferation and cytokine production in macrophages and inhibited apoptosis. Through dual-luciferase assays and RNA pull-down assays, we demonstrated that hsa_circ_0000652 acted as a competing endogenous RNA (ceRNA) by binding with hsa-miR-1179 and regulated OX40L, which is characterized as a co-stimulatory molecule and found to be upregulated in AS patients. As a result, hsa_circ_0000652 aggravated the inflammation in the coculture system containing CD4
T cells and macrophages via OX40/OX40L interaction. Our findings suggest that hsa_circ_0000652 was upregulated in AS patients and may serve as a pro-inflammatory factor in macrophages and a positive regulator of OX40/OX40L by sponging hsa-miR-1179.
Macrophages activation is crucial in pathogenesis of rheumatic diseases like ankylosing spondylitis (AS). Circular RNAs (circRNAs)-induced macrophage-associated inflammation participates in many ...autoimmune diseases but remains elusive in AS. Here, we verified increased expression of circIFNGR2 in peripheral blood mononuclear cells from patients with AS and its expression levels were correlated with the AS severity. In vitro assays revealed that circIFNGR2 enhances macrophage proliferation, and regulates M1/M2 macrophage polarization and NF-κB/Akt pathways. We identified that circIFNGR2 promoted the expression of iNOS/TNFα and M1 polarization, and restrained M2 polarization by sponging miR-939. Additionally, the RNA-binding protein, eIF4A3, was found to enhance the production of circIFNGR2. Interestingly, miR-939 attenuated joint damage in collagen-induced arthritis mice, whereas circIFNGR2 reversed this effect. Our findings highlight the pro-inflammatory roles of eIF4A3-induced circIFNGR2 in AS by modulating macrophage-associated inflammation through miR-939.
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•CircIFNGR2 is associated with disease status of ankylosing spondylitis•CircIFNGR2 promotes M1 macrophage but restrains M2 macrophage polarization•EIF4A3-induced circIFNGR2 regulates macrophage-associated inflammation via miR-939•CircIFNGR2/miR-939 collaboratively regulated inflammatory arthritis
Clinical genetics; Pathophysiology; Disease
Increasing evidence suggests that the pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with FUN14 domain protein 1 (FUNDC1)-mediated mitophagy. Recently, studies have ...reported that puerarin has protective effects against excessive oxidative damage in cells. Therefore, we hypothesized that puerarin may be involved in COPD progression via regulating FUNDC1 mediated mitophagy. We found that the viability of cigarette smoke extract (CSE)-stimulated human bronchial epithelial cells (HBECs) was enhanced and apoptosis was reduced after treatment with different concentrations of puerarin. Puerarin reversed mitochondrial membrane potential (MMP) levels and ATP content, and decreased reactive oxygen species (ROS) content in CSE stimulated HBECs. Moreover, puerarin significantly inhibited apoptosis related proteins, as well as the expression of mitophagy related proteins. After inhibition of FUNDC1 phosphorylation by protein phosphatase inhibitor (PH0321), puerarin restored MMP level, decreased ROS content, promoted ATP synthesis, and downregulated autophagy related protein expression in HBECs. In addition, mitochondrial division inhibitor (Mdivi) inhibited the expression of autophagy related proteins and reduced apoptosis after blocking cell autophagy, which was the same as the inhibition of puerarin. Finally, puerarin activated the PI3K/Akt/mTOR signaling pathway to participate in COPD progression by up regulating the phosphorylation levels of PI3K, Akt and mTOR.
•Mechanical overloading is regarded as the key feature and major trigger of osteoarthritis pathogenesis.•Chondrocyte mitochondrial dysfunction acts as an important hallmark of ...osteoarthritis.•Mechanisms underlying the mitochondrial function alteration induced by mechanical stimulation are barely known.•Further research on AMPK function may provide more insights in the pathogenesis of mechanical loading-induced OA.
Mechanical loading is essential for chondrocyte health. Chondrocytes can sense and respond to various extracellular mechanical signals through an integrated set of mechanisms. Recently, it has been found that mitochondria, acting as critical mechanotransducers, are at the intersection between extracellular mechanical signals and chondrocyte biology. Much attention has been focused on identifying how mechanical loading-induced mitochondrial dysfunction contributes to the pathogenesis of osteoarthritis. In contrast, little is known regarding the mechanisms underlying functional alterations in mitochondria induced by mechanical stimulation. In this review, we describe how chondrocytes perceive environmental mechanical signals. We discuss how mechanical load induces mitochondrial functional alterations and highlight the major unanswered questions in this field. We speculate that AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis, may play an important role in coupling force transmission to mitochondrial health and intracellular biological responses.
Within a density-dependent relativistic mean-field model and using in-medium meson-hadron coupling constants and meson masses, we explore the effects of in-medium hyperon interactions on the ...properties of neutron stars. We found that hyperonic constituents in large-mass neutron stars cannot be simply ruled out, while the recently measured mass of the millisecond pulsar J1614-2230 can significantly constrain in-medium hyperon interactions. In addition, we discuss the effects of nuclear symmetry energy on hyperonization in neutron stars.
In this work, we have systemically investigated the ground-state properties of the rare-earth even–even nuclei with the parameter set FSUGold that includes the isoscalar–isovector coupling to soften ...the symmetry energy. It is the first time that this parameter set is applied to investigate the properties of deformed nuclei. The present study is mainly focused on the nuclei with the known experimental binding energies ranging from
Z
=
58
to
Z
=
70
. The calculated binding energies, quadrupole deformations, and charge radii are in good agreement with the available experimental data. It has been shown that the parameter set FSUGold is as successful as the NL3 in reproducing the known ground-state properties of deformed nuclei.
Effects of the density dependence of the nuclear symmetry energy on ground-state properties of superheavy nuclei are studied in the relativistic mean-field theory. It is found that the softening of ...the symmetry energy plays an important role in the empirical shift Phys. Rev. C 67, 024309 (2003) of spherical orbitals in superheavy nuclei. The calculation based on the relativistic mean-field models NL3 and FSUGold supports the double shell closure in {sup 292}120 with the softening of the symmetry energy. In addition, the significant effect of the density dependence of the symmetry energy on the neutron skin thickness in superheavy nuclei is investigated.
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