ABSTRACT
Simultaneously elevating loading and activity of single atoms (SAs) is desirable for SA-containing catalysts, including single-atom catalysts (SACs). However, the fast self-nucleation of SAs limits the loading, and the activity is confined by the adsorption-energy scaling relationships on monotonous SAs. Here, we theoretically design a novel type of SA-containing catalyst generated by two-step structural self-regulation. In the thermodynamic self-regulation step, divacancies in graphene spontaneously pull up SAs from transition metal supports (dv-g/TM; TM = fcc Co, hcp Co, Ni, Cu), leading to the expectably high loading of SAs. The subsequent kinetic self-regulation step involving an adsorbate-assisted and reversible vacancy migration dynamically alters coordination environments of SAs, helping circumvent the scaling relationships, and consequently, the as-designed dv-g/Ni can catalyze NO-to-NH3 conversion at a low limiting potential of -0.25 V vs RHE.
ABSTRACT
BACKGROUND AND OBJECTIVE: Bone loss occurs in several inflammatory diseases because of chronic persistent inflammation that activates osteoclasts (OCs) to increase bone resorption. Currently available antiresorptive drugs have severe side effects or contraindications. Herein, we explored the effects and mechanism of Alpinetin (Alp) on receptor activator of nuclear factor κB ligand (RANKL)-mediated OCs differentiation, function, and in inflammatory osteolysis of mice. METHOD: Primary mouse bone marrow-derived macrophages (BMMs) induced by RANKL and macrophage colony-stimulating factor (M-CSF) were utilized to test the impact of Alp on OCs differentiation, function, and intracellular reactive oxygen species (ROS) production, respectively. Expression of oxidant stress relevant factors and OCs specific genes were assessed via real-time quantitative PCR. Further, oxidative stress-related factors, NF-κB, MAPK, PI3K/AKT/GSK3-ß, and NFATc1 pathways were examined via Western blot. Finally, LPS-induced mouse calvarial osteolysis was used to investigate the effect of Alp on inflammatory osteolysis in vivo. RESULT: Alp suppressed OCs differentiation and resorption function, and down-regulated the ROS production. Alp inhibited IL-1ß, TNF-α and osteoclast-specific gene transcription. It also blocked the gene and protein expression of Nox1 and Keap1, but enhanced Nrf2, CAT, and HO-1 protein levels. Additionally, Alp suppressed the phosphorylation of PI3K and P38, and restrained the expression of osteoclast-specific gene Nfatc1 and its auto-amplification, hence minimizing LPS-induced osteolysis in mice. CONCLUSION: Alp is a novel candidate or therapeutics for the osteoclast-associated inflammatory osteolytic ailment.
Subject(s)
Bone Density Conservation Agents , Osteolysis , Animals , Bone Density Conservation Agents/pharmacology , Cell Differentiation , Flavanones , Glycogen Synthase Kinase 3/metabolism , Inflammation/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Lipopolysaccharides/pharmacology , Macrophage Colony-Stimulating Factor/metabolism , Macrophage Colony-Stimulating Factor/pharmacology , Macrophage Colony-Stimulating Factor/therapeutic use , Mice , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Osteoclasts , Osteolysis/chemically induced , Osteolysis/drug therapy , Oxidants/metabolism , Oxidants/pharmacology , Oxidants/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RANK Ligand/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Chinese herbal medicine has well-established therapeutic effects in various diseases. Corilagin (Cor), a gallic acid tannin in Phyllanthus niruri L., has anti-inflammatory and antioxidant effects in many diseases. However, its role in osteoclast-related bone diseases has not been determined. In vitro, bone marrow macrophages (BMMs) were extracted and isolated to differentiate into osteoclasts. The effects of Cor on osteoclast formation, bone resorption, and reactive oxygen species (ROS) production were performed. In addition, quantitative real-time polymerase chain reaction and western blot analysis were used to evaluate the effect of Cor on oxidative stress-related pathways, which are nuclear factors-κB ligand-receptor activator (RANKL) stimulates important downstream pathways. Furthermore, microcomputed tomography and bone histomorphometry were performed to analyze the therapeutic effect of Cor in mouse models of lipopolysaccharide (LPS)-mediated bone defects in vivo. Cor influenced the nuclear factor of activated T cells 1 (NFATc1) signaling pathway and reduced ROS in RANKL-treated osteoclasts, thereby inhibiting osteoclast formation and bone resorption. Moreover, Cor protected against LPS-mediated skull defects in vivo. In sum, our results confirm that Cor can inhibit osteoclastogenesis and intracellular oxidative stress. In addition, the inflammatory bone defect induced by LPS was also attenuated by Cor. Accordingly, Cor is a new candidate therapeutic agent for osteoclast-mediated osteolytic diseases.
Subject(s)
Osteoclasts , Osteolysis , Animals , Cell Differentiation , Glucosides , Hydrolyzable Tannins , Lipopolysaccharides/pharmacology , Mice , Mice, Inbred C57BL , Osteoclasts/metabolism , Osteogenesis , Osteolysis/chemically induced , Osteolysis/drug therapy , Osteolysis/metabolism , Reactive Oxygen Species/metabolism , X-Ray MicrotomographyABSTRACT
OBJECTIVE: Closed reduction of pelvic injuries is a prerequisite and critical step in minimally invasive treatment. Achieving non-invasive closed reduction of pelvic injuries is a challenging clinical problem. This study demonstrated a non-invasive traction technique for closed reduction called countertraction closed reduction technique (CCRT) and evaluated its effectiveness for type C pelvic ring injuries. METHOD: The data of patients with unstable pelvic fractures treated with CCRT and minimally invasive fixation were retrospectively reviewed from January 2017 to February 2022. Sacroiliac screws were placed to fix the posterior pelvic ring, and internal or external fixation was used to fix the anterior pelvic ring. Operation time, intraoperative blood loss, duration of hospital stay, fracture union and postoperative complications were recorded. Fracture reduction quality was evaluated using the Matta scoring criteria. Functional recovery and general quality of life were evaluated using the Majeed functional scoring criteria. RESULTS: Thirteen patients (nine males and four females), with an average age of 49.6 years were treated with CCRT and followed up for a mean of 18.5 months. The average operation time was 137.2 minutes (range 92-195 minutes), the average intraoperative blood loss was 31.2 mL (range 10-120 mL) and the average duration of hospital stay was 14.3 days (range 4-32 days). All patients achieved bony union with an average union time of 11.9 weeks (range 10-16 weeks). According to the Matta radiographic criteria, the quality of fracture reduction was excellent in eight patients, good in four, and fair in one. The average Majeed functional score was 89.7 (range 78-100). The functional evaluation revealed that the outcomes were excellent in nine patients, and good in four patients. Complications included incision fat liquefaction in one patient, and heterotopic ossification in another patient. There were no surgical complications as a result of CCRT. CONCLUSION: CCRT is a non-invasive closed reduction method for minimally invasive fixation of fresh Tile C1 and C2 pelvic fractures. The advantages of CCRT combined with minimally invasive treatment include a small surgical incision, reduced intraoperative bleeding, satisfactory fracture reduction, bone healing and functional recovery.
Subject(s)
Fractures, Bone , Pelvic Bones , Male , Female , Humans , Middle Aged , Fracture Fixation, Internal/methods , Retrospective Studies , Blood Loss, Surgical , Quality of Life , Fractures, Bone/surgery , Pelvic Bones/surgery , Pelvic Bones/injuries , Treatment OutcomeABSTRACT
Heterotopic ossification (HO) denotes the presence of mature bone tissue in soft tissues or around joints. Inflammation is a key driver of traumatic HO, and macrophages play an important role in this process. Ethyl caffeate (ECF), a critical active compound found in Petunia, exerts significant anti-inflammatory effects. Herein, we established a mouse model of HO by transection of the Achilles tendon and back burn and found abundant macrophage infiltration in the early stage of HO, which decreased with time. In vitro and in vivo experiments indicated that ECF inhibited macrophage polarization, and mechanistic studies showed that it inhibited the SIRT1/NF-κB signalling pathway, thereby suppressing the release of downstream inflammatory cytokines. ECF reduced HO in mice, and its effect was comparable to indomethacin (INDO). In vitro studies revealed that ECF did not directly affect the mineralization of mesenchymal stem cells (MSCs) or osteogenic differentiation but inhibited these processes by reducing the level of inflammatory cytokines in the conditioned medium (CM). Thus, M1 macrophages may play a crucial role in the pathogenesis of HO, and ECF is a prospective candidate for the prevention of trauma-induced HO. DATA AVAILABILITY: Data will be made available on request.
Subject(s)
NF-kappa B , Ossification, Heterotopic , Mice , Animals , NF-kappa B/metabolism , Osteogenesis , Sirtuin 1 , Macrophages/metabolism , Cytokines/pharmacologyABSTRACT
BACKGROUND: Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are widely used for the treatment of medial unicompartmental knee osteoarthritis (OA). However, the best approach remains controversial. This study aimed to present a systematic review and a meta-analysis to directly compare the clinical outcomes between HTO and UKA. We hypothesized that the clinical outcomes after UKA and HTO would be similar. METHODS: Electronic databases (Web of Science, PubMed, Embase, CENTRAL, and Biosis Preview) were searched for related studies published before November 30, 2021. Retrospective and prospective studies that directly compared the postoperative outcomes between UKA and HTO were included. Odds ratio (ORs) and 95% confidence interval (CIs) for complications, revision to total knee arthroplasty (TKA), and weighted mean difference (MD) and 95% CIs in range of motion (ROM), pain, walking speed and function score were evaluated. Two reviewers independently assessed the quality of the studies. Subgroup and sensitivity analyses were performed to explore the heterogeneity. RESULTS: Twenty-three retrospective and 6 prospective studies were included. A total of 3004 patients (3084 knees) were evaluated for comparison. Complications (OR, 4.88, 95% CI: 2.92-6.86) were significantly greater in the HTO group than in the UKA group. Postoperative function scores including Lysholm score (MD, -2.78, 95% CI: -5.37 to -0.18) and Hospital for Special Surgery (HSS) score (MD, -2.80, 95% CI: -5.39 to -0.20) were significantly lower in the HTO group than the UKA group. The postoperative ROM was similar between HTO and mobile-bearing UKA (MD, -3.78, 95% CI: -15.78 to 8.22). However, no significant differences were observed between the HTO and UKA group in terms of postoperative pain, walking speed, and revision to TKA. CONCLUSIONS: UKA is superior to HTO in minimizing complications and enhancing postoperative function scores. Mobile-bearing UKA has a similar ROM compared with HTO. Both HTO and UKA provide satisfactory clinical outcomes in terms of walking speed, relieving pain, and revision to TKA. UKA appears to be more suitable for the elderly, and both mobile-bearing UKA and HTO are viable surgical options for younger active individuals.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Aged , Arthroplasty, Replacement, Knee/adverse effects , Humans , Knee Joint/surgery , Osteoarthritis, Knee/complications , Osteotomy/adverse effects , Pain, Postoperative/etiology , Prospective Studies , Reoperation/adverse effects , Retrospective Studies , Tibia/surgery , Treatment OutcomeABSTRACT
Wear debris after total joint arthroplasty can attract the recruitment of macrophages, which release pro-inflammatory substances, triggering the activation of osteoclasts, thereby leading to periprosthetic osteolysis (PPOL) and aseptic loosening. However, the development of pharmacological strategies targeting osteoclasts to prevent periprosthetic osteolysis has not been fruitful. In this study, we worked toward researching the effects and mechanisms of a farnesyltransferase (FTase) inhibitor Lonafarnib (Lon) on receptor activator of nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis and bone resorption, as well as the impacts of Lon on titanium particle-induced osteolysis. To investigate the impacts of Lon on bone resorption and osteoclastogenesis in vitro, bone marrow macrophages were incubated and stimulated with RANKL and macrophage colony-stimulating factor (M-CSF). The influence of Lon on osteolysis prevention in vivo was examined utilizing a titanium particle-induced mouse calvarial osteolysis model. The osteoclast-relevant genes expression was explored by real-time quantitative PCR. Immunofluorescence was used to detect intracellular localization of nuclear factor of activated T cells 1 (NFATc1). SiRNA silence assay was applied to examine the influence of FTase on osteoclasts activation. Related signaling pathways, including NFATc1 signaling, NF-κB, mitogen-activated protein kinases pathways were identified by western blot assay. Lon was illustrated to suppress bone resorptive function and osteoclastogenesis in vitro, and it also reduced the production of pro-inflammatory substances and prevented titanium particle-induced osteolysis in vivo. Lon decreased the expression of osteoclast-relevant genes and suppressed NFATc1 nuclear translocation and auto-amplification. Mechanistically, Lon dampened FTase, and inhibition of FTase reduced osteoclast formation by suppressing ERK signaling. Lon is a promising treatment option for osteoclast-related osteolysis diseases including periprosthetic osteolysis by targeted inhibition of FTase through suppressing ERK signaling.
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OBJECTIVES: To discuss the mutational features and their relationships with disease in a family with hereditary multiple osteochondroma (HMO) from Guangxi Province (GXBB-1 family), China. METHODS: Genomic DNA and total mRNA were extracted from peripheral blood cells of GXBB-1 family members. Whole elements of the EXT1gene and its transcript, including exons, introns, exon-intron boundaries, and coding sequence (CDS) clones, were amplified and sequenced. Allele-specific PCR was used to confirm the position and type of mutation. RESULTS: All patients from the GXBB-1 family harbored the cosegregating heterozygous c.1056+1G>A mutation located in EXT1at an exon-intron boundary. Another three single-nucleotide polymorphisms (SNPs) were also detected in the patients, including IVS2+1G>A in intron 2, c.1844 T>C [p.Pro (CCT) 614Pro (CCC)] in exon 3, and c.2534G>A [p.Glu (GAG) 844Glu (GAA)] in exon 9. The latter two SNPs were synonymous variations. CONCLUSIONS: The heterozygous c.1056+1G>A mutation cosegregated with the phenotype, indicating that it is a pathogenic mutation in the GXBB-1 family. This mutation is reported for the first time in Chinese HMO patients. IVS2+1G>A and c.2534G>A have no relationship with the occurrence of disease. However, c.1844 T>C and c.1056+1G>A are linked, and their interaction needs to be further studied. c.1844T>C is a new SNP that has not been reported internationally.