Notch signaling regulates macrophage-mediated inflammation in metabolic dysfunction-associated steatotic liver disease.

The liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and functions in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing (scRNA-seq) and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH.

Infection microenvironment-triggered nanoparticles eradicate MRSA by thermally amplified chemodynamic therapy and M1 macrophage.

It is of great significance to develop a novel approach to treat bacterial infections, as the frequent misuse of antibiotics leads to the serious problem of bacterial resistance. This study proposed antibiotic-free antibacterial nanoparticles for eliminating methicillin-resistant Staphylococcus aureus (MRSA) based on a multi-model synergistic antibacterial ability of chemodynamic therapy (CDT), photothermal effect, and innate immunomodulation. Specifically, a polydopamine (PDA) layer coated and Ag nanoparticles loaded core-shell structure FeO nanoparticles (FeO@PDA-Ag) is prepared.

Identification of key candidate genes and pathways in rheumatoid arthritis and osteoarthritis by integrated bioinformatical analysis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common joint disorders. Although they have shown analogous clinical manifestations, the pathogenesis of RA and OA are different. In this study, we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE153015 to identify gene signatures between RA and OA joints.

Approaches to Biofunctionalize Polyetheretherketone for Antibacterial: A Review.

Due to excellent mechanical properties and similar elastic modulus compared with human cortical bone, polyetheretherketone (PEEK) has become one of the most promising orthopedic implant materials. However, implant-associated infections (IAIs) remain a challenging issue since PEEK is bio-inert. In order to fabricate an antibacterial bio-functional surface, modifications of PEEK had been widely investigated.

Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection.

Orthopedic implants account for 99% of orthopedic surgeries, however, orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality. Current antibiotic treatments still lack the capacity to target bone infection sites, thereby resulting in unsatisfactory therapeutic effects. Here, the bone infection site targeting efficacy of D6 and UBI peptides was investigated, and bone-and-bacteria dual-targeted nanoparticles (NPs) with D6 and UBI peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site.

p300/CBP inhibitor A-485 inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss.

Osteoporosis is one of the most common metabolic bone diseases among pre- and post-menopausal women. Despite numerous advances in the treatment of osteoporosis in recent years, the outcomes remain poor due to severe side effects. In this study, we investigated whether A-485, a highly selective catalytic p300/CBP inhibitor, could attenuate RANKL-induced osteoclast differentiation and explored the underlying molecular mechanisms.

Overcoming Planktonic and Intracellular -Associated Infection with a Cell-Penetrating Peptide-Conjugated Antimicrobial Peptide.

is a primary pathogen responsible for causing postoperative infections as it survives and persists in host cells, including osteoblasts and macrophages. These cells then serve as reservoirs resulting in chronic infections. Most traditional antibiotics have poor effects on intracellular because they cannot enter the cell.

KR-12 coating of polyetheretherketone (PEEK) surface polydopamine improves osteointegration and antibacterial activity .

Polyetheretherketone (PEEK) is considered to be a promising bone implant material owing to its biocompatibility and elastic modulus, which is similar to that of natural bone. However, the clinical potential of PEEK is severely limited by its bioinertness, which leads to poor osseointegration, and the lack of antibacterial properties. In this study, the antimicrobial peptide, KR-12, was immobilized on the surface of PEEK implants with the assistance of polydopamine (PDA) to inhibit bacterial infection as well as to promote osteogenesis and osseointegration.

Hydrofluoric acid and nitric acid cotreatment for biofunctionalization of polyetheretherketone in M2 macrophage polarization and osteogenesis.

Due to its excellent mechanical and low-friction properties, polyetheretherketone (PEEK) has been widely investigated for use in orthopedic applications over the past decade. However, the bioinertness and poor osteogenic properties of PEEK have hampered its clinical application. In this study, the surface of PEEK was modified by co-treatment with hydrofluoric acid and nitric acid (AFN).

Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are one of the most serious surgery complications, and their prevention is of utmost importance. Flufenamic acid is a non-steroid anti-inflammatory drug approved for clinical use to relieve inflammation and pain in rheumatoid arthritis patients. In this study, we explored the antibacterial efficacy of flufenamic acid and the mechanisms underlying this effect.

Improved antibacterial properties of collagen I/hyaluronic acid/quaternized chitosan multilayer modified titanium coatings with both contact-killing and release-killing functions.

Implant infection is one of the most severe complications after orthopedic surgery. The construction of an antibacterial coating on orthopedic implants with release-killing or contact-killing is one of the most efficient strategies to prevent implant-related infections. Here we reported a hydroxypropyltrimethyl ammonium chloride chitosan (HACC) based multilayer modified plasma-sprayed porous titanium coating generated via the layer-by-layer covalent-immobilized method.

Trends in Bone Mineral Density, Osteoporosis, and Osteopenia Among U.S. Adults With Prediabetes, 2005-2014.

Objective: We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture.

Effects of staphylococcal infection and aseptic inflammation on bone mass and biomechanical properties in a rabbit model.

Background/objective: Orthopaedic implants are important devices aimed at relieving pain and improving mobility. Staphylococcal infection and aseptic loosening are two common events associated with inflammatory osteolysis that lead to implant failures. Bone mass and biomechanical properties are important indicators that could influence patient outcomes after revision surgery.

Flufenamic acid inhibits osteoclast formation and bone resorption and act against estrogen-dependent bone loss in mice.

Postmenopausal osteoporosis is one of the most common types of osteoporosis resulting from estrogen deficiency in elderly women. Nonsteroidal anti-inflammatory drugs (NSAIDs) are important drugs for pain relief in patients with osteoporosis. In this study, we report for the first time that flufenamic acid, a clinically approved and widely used NSAID, not only has analgesic properties but also shows a significant effect in terms of preventing postmenopausal osteoporosis.

KR-12-a5 Reverses Adverse Effects of Lipopolysaccharides on HBMSC Osteogenic Differentiation by Influencing BMP/Smad and P38 MAPK Signaling Pathways.

KR-12-a5 is an analogue of the antimicrobial peptide KR-12. Both of these two agents can play key effects in the treatment of infections such as osteomyelitis. Our previous work demonstrated that the osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs) can be enhanced by KR-12.

Effects of magnesium coating on bone-implant interfaces with and without polyether-ether-ketone particle interference: A rabbit model based on porous Ti6Al4V implants.

We investigated the effects of magnesium (Mg) on osteogenesis and bone resorption at a porous structure interface. A three-dimensional (3D)-printed porous Ti6Al4V implant coated with Mg was introduced, and polyether-ether-ketone wear particles were added to generate an animal model of implant loosening. We also examined the effects of Mg leach liquor on osteoblast/osteoclast gene expression, alkaline phosphatase activity, collagen secretion, tartrate-resistant acid phosphatase activity, and bone resorption in vitro.

Immobilization of type I collagen/hyaluronic acid multilayer coating on enoxacin loaded titania nanotubes for improved osteogenesis and osseointegration in ovariectomized rats.

Titania nanotubes (Ti-NTs) have been proven to be good drug carriers and can release drugs efficiently around implants. Enoxacin (EN) is a broad-spectrum antibiotic that has the ability of anti-osteoclastogenesis. Immobilization of extracellular matrix components on the surface of the material can greatly enhance the biological activity of the implant and slow down the release rate of the drug in Ti-NTs.

The antimicrobial peptide KR-12 promotes the osteogenic differentiation of human bone marrow stem cells by stimulating BMP/SMAD signaling.

KR-12 is the smallest fragment of human antimicrobial peptide cathelicidin (LL-37), and could play key roles in the treatment of multiple infections, including osteomyelitis. Our preliminary work found that KR-12 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs). The present study investigated whether KR-12 affects HBMSC osteogenic differentiation, as well as the molecular mechanisms involved.

Bacitracin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by stimulating the bone morphogenetic protein-2/Smad axis.

Bacitracin, a widely used metallopeptide antibiotic, has been reported to be locally used in treating wounds without systemic adverse reactions. Our preliminary study showed that bacitracin might enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs). The present study investigated whether bacitracin affects the osteogenic differentiation of HBMSCs and the molecular mechanisms involved.

Approaches based on passive and active antibacterial coating on titanium to achieve antibacterial activity.

Titanium (Ti) and its alloys are widely applied as orthopedic implants for hip and knee prosthesis, fixation, and dental implants. However, Ti and its alloys are bioinert and susceptible to bacteria and biofilm formation. Strategies for improving the antibacterial properties of Ti can be divided into two approaches, namely, passive coating and active coating on the Ti surface.

How to accurately determine the distal femoral valgus cut angle in the valgus knee arthroplasty.

Purpose: Distal femoral resection in total knee arthroplasty (TKA) is commonly performed using intramedullary jigs with a pre-operatively planned valgus cut angle (VCA). For valgus knees with lateral femoral condyle hypoplasia, the method of determining the accurate VCA has not been clarified. The aim of the present study is to introduce a method that can accurately determine the distal femoral VCA in the valgus knee arthroplasty.