Deciphering the pathogenic role of rare RAF1 heterozygous missense mutation in the late-presenting DDH.

Background: Developmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic basis of DDH is not fully understood despite known genetic predispositions. Methods: We employed Whole Genome Sequencing (WGS) to explore the genetic factors in late-presenting DDH in two unrelated families, supported by phenotypic analyses and in vitro validation. Results: In both cases, a novel de novo heterozygous missense mutation in RAF1 (c.193A>G [p.Lys65Glu]) was identified. This mutation impacted RAF1 protein structure and function, altering downstream signaling in the Ras/ERK pathway, as demonstrated by bioinformatics, molecular dynamics simulations, and in vitro validations. Conclusion: This study contributes to our understanding of the genetic factors involved in DDH by identifying a novel mutation in RAF1. The identification of the RAF1 mutation suggests a possible involvement of the Ras/ERK pathway in the pathogenesis of late-presenting DDH, indicating its potential role in skeletal development.

A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM.

Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.

Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.

Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by traumatic brain injury, spinal cord injury, and burns. Despite a wide range of evidence underscoring the significance of neurogenic signals in proper bone remodeling, a clear understanding of HO induced by nerve injury remains rudimentary. Recent studies suggest that injury to the nervous system can activate various signaling pathways, such as TGF-ß, leading to neurogenic HO through the release of neurotrophins. These pathophysiological changes lay a robust groundwork for the prevention and treatment of HO. In this review, we collected evidence to elucidate the mechanisms underlying the pathogenesis of HO related to nerve injury, aiming to enhance our understanding of how neurological repair processes can culminate in HO.

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.

Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to joint pain, disability, and a diminished quality of life. Although considerable research has been conducted, the precise molecular mechanisms propelling OA pathogenesis continue to be elusive, thereby impeding the development of effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in the early stage of OA. This development is marked by escalated osteoclast-mediated bone resorption, subsequent imbalances in bone metabolism, accelerated bone turnover, and a decrease in bone volume, thereby contributing significantly to the pathological changes. While the role of aging hallmarks in OA has been extensively elucidated from the perspective of chondrocytes, their connection with osteoclasts is not yet fully understood. There is compelling evidence to suggest that age-related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, and mitochondrial dysfunction, can stimulate osteoclast activity. This review intends to systematically discuss how aging hallmarks contribute to OA pathogenesis, placing particular emphasis on the age-induced shifts in osteoclast activity. It also aims to stimulate future studies probing into the pathological mechanisms and therapeutic approaches targeting osteoclasts in OA during aging.

Association between combined exposure to dioxins and arthritis among US adults: a cross-sectional study.

Dioxins and dioxin-like compounds (DLCs) are common pollutants hazardous to human health. We applied 12 dioxins and DLCs data of 1851 participants (including 484 arthritis patients) from National Health Examination Survey (NHANES) 2001-2004 and quadrupled them into rank variables. Multivariate logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were used to explore the relationship between individual or mixed exposure to the pollutants and arthritis after adjusting for multiple covariates. In multivariable logistic regression with an individual dioxin or DLC, almost every chemical was significantly positively associated with arthritis, except PCB66 (polychlorinated biphenyl 66) and 1,2,3,4,6,7,8-heptachlorodibenzofuran (hpcdf). The WQS model indicated that the combined exposure to the 12 dioxins and DLCs was positively linked to arthritis (OR: 1.884, 95% CI: 1.514-2.346), with PCB156 (weighted 0.281) making the greatest contribution. A positive trend between combined exposure and arthritis was observed in the BKMR model, with a posterior inclusion probability (PIP) of 0.987 for PCB156, which was also higher than the other contaminants.

Inhibition of Protein Disulfide Isomerase Attenuates Osteoclast Differentiation and Function via the Readjustment of Cellular Redox State in Postmenopausal Osteoporosis.

Due to the accumulation of reactive oxygen species (ROS) and heightened activity of osteoclasts, postmenopausal osteoporosis could cause severe pathological bone destruction. Protein disulfide isomerase (PDI), an endoplasmic prototypic thiol isomerase, plays a central role in affecting cellular redox state. To test whether suppression of PDI could inhibit osteoclastogenesis through cellular redox regulation, bioinformatics network analysis was performed on the causative genes, followed by biological validation on the osteoclastogenesis in vitro and ovariectomy (OVX) mice model in vivo. The analysis identified PDI as one of gene targets for postmenopausal osteoporosis, which was positively expressed during osteoclastogenesis. Therefore, PDI expression inhibitor and chaperone activity inhibitor were used to verify the effects of PDI inhibitors on osteoclastogenesis. Results demonstrated that PDI inhibitors could reduce osteoclast number and inhibit resorption function via suppression on osteoclast marker genes. The mechanisms behind the scenes were the PDI inhibitors-caused intracellular ROS reduction via enhancement of the antioxidant system. Micro-CT and histological results indicated PDI inhibitors could effectively alleviate or even prevent bone loss in OVX mice. In conclusion, our findings unveiled the suppressive effects of PDI inhibitors on osteoclastogenesis by reducing intracellular ROS, providing new therapeutic options for postmenopausal osteoporosis.

[Retracted] Acetylsalicylic acid combined with diclofenac inhibits cartilage degradation in rabbit models of osteoarthritis.

[This retracts the article DOI: 10.3892/etm.2016.3560.].

Macrophages in aseptic loosening: Characteristics, functions, and mechanisms.

Aseptic loosening (AL) is the most common complication of total joint arthroplasty (TJA). Both local inflammatory response and subsequent osteolysis around the prosthesis are the fundamental causes of disease pathology. As the earliest change of cell behavior, polarizations of macrophages play an essential role in the pathogenesis of AL, including regulating inflammatory responses and related pathological bone remodeling. The direction of macrophage polarization is closely dependent on the microenvironment of the periprosthetic tissue. When the classically activated macrophages (M1) are characterized by the augmented ability to produce proinflammatory cytokines, the primary functions of alternatively activated macrophages (M2) are related to inflammatory relief and tissue repair. Yet, both M1 macrophages and M2 macrophages are involved in the occurrence and development of AL, and a comprehensive understanding of polarized behaviors and inducing factors would help in identifying specific therapies. In recent years, studies have witnessed novel discoveries regarding the role of macrophages in AL pathology, the shifts between polarized phenotype during disease progression, as well as local mediators and signaling pathways responsible for regulations in macrophages and subsequent osteoclasts (OCs). In this review, we summarize recent progress on macrophage polarization and related mechanisms during the development of AL and discuss new findings and concepts in the context of existing work.

Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

RNA expression profiling from the liquid fraction of synovial fluid in knee joint osteoarthritis patients.

OBJECTIVE: To investigate the RNA profile of synovial fluid (SF) from osteoarthritis (OA) patients and carry out cluster analysis of OA-related genes. METHODS: RNA of SF from OA patients was isolated using RNA-specific Trizol. A cDNA library was built and subjected to the second-generation sequencing using HisSeq4000 with a data size of 8G. The sequencing reads were aligned to the UCSC human reference genome (hg38) using Tophat with default parameters. Gene function enrichment was generated using DAVID. RESULTS: The minimum weight 0.096 µg RNA of SF sample was used for sequencing analysis, which produced 66,154,562 clean reads, 91.28% of which were matched to the reference with 2,682 genes identified. Some of the unmatchable reads matched RNAs of bacteria, mainly Pseudomonas. The detected human RNAs in samples fell into different categories of genes, including protein-coding ones, processed and unprocessed pseudogenes, and long noncoding, antisense and miscellaneous RNAs that mediate various biological functions. Interestingly, 80% of the expressed genes belonged to the mitochondrial genome. CONCLUSION: These results suggest that less than 0.1 µg RNA is sufficient for establishing a cDNA library and deep sequencing, and that the liquid fraction of SF contains a whole RNA repertoire that may reflect a history of previous microorganism infections.

Wnt3a knockdown promotes collagen type II expression in rat chondrocytes.

Osteoarthritis (OA) is a chronic condition caused by cartilage degradation, and there are currently no effective methods for preventing the progression of this disease; gene therapy is a relatively novel method for treating arthritis. Decreased collagen type II (Col2) expression within the cartilage matrix is an important factor for the development of OA, and Wnt3a serves a significant role in cartilage homeostasis. The present study assessed whether Wnt3a knockdown promoted Col2 expression in chondrocytes. Lentivirus-introduced small interfering RNA was used to knock down the expression of Wnt3a in primary rat chondrocytes, and then IL-1ß treatment was used to establish an OA chondrocyte model. The expression of target genes (Wnt3a, Col2, MMP-13 and ß-catenin) was analyzed using reverse transcription-quantitative PCR, western blotting and immunocytochemistry. There was significantly less MMP-13 and ß-catenin expression in the Wnt3a knockdown cells compared with the other controls. Col2 expression was significantly higher in the Wnt3a-knockdown cells compared with the control cells, indicating that knockdown of Wnt3a may promote Col2 expression. Consequently, Wnt3a was indicated to be an important factor in cartilage homeostasis, and Wnt3a knockdown may serve as a novel method for OA therapy.

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance.

Oxidative stress involves enormously in the development of chronic inflammatory bone disease, wherein the overproduction of reactive oxygen species (ROS) negatively impacts the bone remodeling via promoting osteoclastogenesis and inhibiting osteogenesis. Lacking effective therapies highlights the importance of finding novel treatments. Our previous study screened a novel bioactive peptide D7 and demonstrated it could enhance the cell behaviors and protect bone marrow mesenchymal stem cells (BMSCs). Since BMSCs are progenitor cells of osteoblast (OB), we therefore ask whether D7 could also protect against the progress of inflammatory osteolysis. To validate our hypothesis and elucidate the underlying mechanisms, we first performed network pharmacology-based analysis according to the molecule structure of D7, and then followed by pharmacological evaluation on D7 by in vitro lipopolysaccharide(LPS)-induced models. The result from network pharmacology identified 20 candidate targets of D7 for inflammatory osteolysis intervention. The further analysis of Gene Ontology (GO)/KEGG pathway enrichment suggested the therapeutic effect of D7 may primarily affect osteoclast (OC) differentiation and function during the inflammatory osteolysis. Through validating the real effects of D7 on OC and OB as postulated, results demonstrated suppressive effects of D7 on LPS-stimulated OC differentiation and resorption, via the inhibition on OC marker genes. Contrarily, by improving the expression of OB marker genes, D7 displayed promotive effects on OB differentiation and alleviated LPS-induced osteogenic damage. Further mechanism study revealed that D7 could reduce LPS-induced ROS formation and strengthen antioxidants expressions in both OC and OB precursors, ameliorating LPS-triggered redox imbalance in bone remodeling. Taken together, our findings unveiled therapeutic effects of D7 against LPS-induced inflammatory osteolysis through the suppression of oxidative stress and the restoration of the bone remodeling process, providing a new therapeutic candidate for chronic inflammatory bone diseases.

Indole alkaloids of Alstonia scholaris (L.) R. Br. alleviated nonalcoholic fatty liver disease in mice fed with high-fat diet.

Alstonia scholaris (L.) R. Br (Apocynaceae) is a well-documented medicinal plant for treating respiratory diseases, liver diseases and diabetes traditionally. The current study aimed to investigate the effects of TA on non-alcoholic fatty liver disease (NAFLD). A NAFLD model was established using mice fed a high-fat diet (HFD) and administered with TA (7.5, 15 and 30 mg/kg) orally for 6 weeks. The biochemical parameters, expressions of lipid metabolism-related genes or proteins were analyzed. Furthermore, histopathological examinations were evaluated with Hematoxylin-Eosin and MASSON staining. TA treatment significantly decreased the bodyweight of HFD mice. The concentrations of low-density lipoprotein (LDL), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also decreased significantly in TA-treated mice group, accompanied by an increase in high-density lipoprotein (HDL). Furthermore, TA alleviated hepatic steatosis injury and lipid droplet accumulation of liver tissues. The liver mRNA levels involved in hepatic lipid synthesis such as sterol regulatory element-binding protein 1C (SREBP-1C), regulators of liver X receptor α (LXRα), peroxisome proliferator activated receptor (PPAR)γ, acetyl-CoA carboxylase (ACC1) and stearyl coenzyme A dehydrogenase-1 (SCD1), were markedly decreased, while the expressions involved in the regulation of fatty acid oxidation, PPARα, carnitine palmitoyl transterase 1 (CPT1A), and acyl coenzyme A oxidase 1 (ACOX1) were increased in TA-treated mice. TA might attenuate NAFLD by regulating hepatic lipogenesis and fatty acid oxidation.

Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that is closely associated with the clinical application of high-dose glucocorticoids. Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7 against ONFH in BMSCs and evaluated the underlying mechanisms. First, we screened for ONFH risk factors. Then, we applied D7 treatment to steroid-induced ONFH (SONFH) in an in vitro model produced by dexamethasone (DEX) to further elucidate the underlying mechanisms. We found negative correlations among oxidative stress marker expression, growth differentiation factor 15 (GDF15) levels, and ONFH. Furthermore, we demonstrated that DEX inhibited the proliferation and induced apoptosis of BMSCs by suppressing GDF15/AKT/mammalian target of rapamycin (mTOR) signaling. D7 alleviated DEX-induced BMSCs injury and restored the chondrogenic function of BMSCs by activating GDF15/AKT/mTOR signaling. In addition, DEX-induced excessive reactive oxygen species (ROS) generation was an upstream trigger of GDF15-mediated signaling, and D7 ameliorated this DEX-induced redox imbalance by restoring the expression of antioxidants, including superoxide dismutase (SOD) 1, SOD2, and catalase, via regulation of GDF15 expression. In conclusion, our findings revealed the potential therapeutic effects of D7 in SONFH and showed that this protective function may be mediated via inhibition of DEX-induced ROS and activation of GDF15/AKT/mTOR signaling, thereby providing insights into the potential applications of D7 in SONFH treatment.

Evaluation of the therapeutic efficacy of human bone marrow mesenchymal stem cells with COX-2 silence and TGF-ß3 overexpression in rabbits with antigen-induced arthritis.

OBJECTIVE: Mesenchymal stem cells (MSCs), especially genetically modified MSCs, have become a promising therapeutic approach for the treatment of rheumatoid arthritis (RA) through modulating immune responses. However, most MSCs used in the treatment of RA are modified based on a single gene. In this study, we evaluated the therapeutic effects of human BMSCs (hBMSCs) with COX-2 silence and TGF-ß3 overexpression in the treatment of RA in a rabbit model. MATERIALS AND METHODS: hBMSCs were cotransfected with shCOX-2 and TGF-ß3 through lentiviral vector delivery. After SPIO-Molday ION Rhodamine-B™ (MIRB) labeling, lenti-shCOX2-TGF-ß3 hBMSCs, lenti-shCOX2 hBMSCs, lenti-TGF-ß3 hBMSCs, hBMSCs without genetic modification, or phosphate-buffered saline (PBS) were injected into the knee joint of rabbits with antigen-induced arthritis (AIA). The diameter of the knee joint and soft-tissue swelling score (STS) were recorded, and the levels of inflammatory mediators, including interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) were evaluated by ELISA. Clinical 3.0T MR imaging (MRI) was used to track the distribution and dynamic migration of hBMSCs in the joint. Histopathological and immunohistochemical assays were conducted to localize labeled hBMSCs and assess the alteration of synovial hyperplasia, inflammatory cell infiltration, and cartilage damage. RESULTS: COX-2 silencing and TGF-ß3 overexpression in hBMSCs were confirmed through real-time PCR and Western blot analyses. Reduced joint diameter, soft-tissue swelling (STS) score, and PGE2, IL-1ß, and TNF-α expression were detected 4 weeks after injection of MIRB-labeled lenti-shCOX2-TGF-ß3 hBMSCs into the joint in rabbits with AIA. Eight weeks after hBMSC injection, reduced inflammatory cell infiltration, improved hyperplasia of the synovial lining, recovered cartilage damage, and increased matrix staining were observed in joints injected with lenti-shCOX2-TGF-ß3 hBMSCs and lenti-shCOX2 hBMSCs. Slight synovial hyperplasia, no surface fibrillation, and strong positive expression of collagen II staining in chondrocytes and cartilage matrix were detected in the joints 12 weeks after injection of lenti-shCOX2-TGF-ß3 hBMSCs. In addition, hBMSCs were detected by MRI imaging throughout the process of hBMSC treatment. CONCLUSION: Intra-articular injection of hBMSCs with COX-2 silence and TGFß3 overexpression not only significantly inhibited joint inflammation and synovium hyperplasia, but also protected articular cartilage at the early stage. In addition, intra-articular injection of hBMSCs with COX-2 silence and TGFß3 overexpression promoted chondrocyte and matrix proliferation. This study provides an alternative therapeutic strategy for the treatment of RA using genetically modified hBMSCs.

miR-590-5p affects chondrocyte proliferation, apoptosis, and inflammation by targeting FGF18 in osteoarthritis.

OBJECTIVE: To investigate the potential miRNA targeting FGF18, and its role in regulating the proliferation, apoptosis and inflammation in human primary chondrocytes. METHODS: The normal human chondrocytes were induced by IL-1ß to mimic OA in vitro. qPCR and Western blotting were performed to evaluate the expression of FGF18. Target Scan analysis was performed to predict the miRNA targeting FGF18. Then, the expression of miR-590-5p was quantified by qPCR in IL-1ß-induced chondrocytes. After transfection of miR-590-5p mimics or inhibitors, CCK-8 assay was conducted to determine the cell viability and apoptosis-related proteins, and cartilage degeneration related biomarkers were assayed by qPCR and Western blotting. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 were determined by ELISA. The targeting relationship between miR-590-5p and FGF18 was assayed by luciferase reporter assay in IL-1ß-induced chondrocytes. RESULTS: Target Scan analysis predicted that FGF18 is directly targeted by miR-590-5p. miR-590-5p was up-regulated, whereas FGF18 expression was inhibited in IL-1ß-induced chondrocytes. miR-590-5p mimics reduced the expression of FGF18 protein, inhibited the cell viability of chondrocytes, and promoted secretion of inflammatory factors in chondrocytes, while miR-590-5p inhibitors increased FGF18 levels in IL-1ß-treated chondrocytes. Furthermore, expression of inflammatory factors in chondrocytes was reduced by miR-590-5p inhibitors. The luciferase reporter assay showed that miR-590-5p could target FGF18. CONCLUSIONS: miR-590-5p promotes OA progression by targeting FGF18, which serves as a potential therapeutic target for OA.

Therapeutic Applications of Nanozymes in Chronic Inflammatory Diseases.

Since the discovery of horseradish peroxidase-like activity of magnetite nanoparticles in 2007, many researchers have investigated different types of nanoparticles that show enzyme-like activities, namely, nanozymes. Nanozymes possess high efficiency, stability, and low production costs compared to natural enzymes. Thus, nanozymes have already been widely studied in various domains including medical science, food industry, chemical engineering, and agriculture. This review presents the utilization of nanozymes in medicine and focuses particularly on their therapeutic applications in chronic inflammatory diseases because of their antioxidant-like activity. Furthermore, the treatment of chronic inflammatory diseases with nanozymes of different materials was introduced emphatically.

Thromboelastography parameters in diagnosing periprosthetic joint infection and predicting reimplantation timing.

BACKGROUND: Coagulation-related biomarkers are drawing new attention in the diagnosis of periprosthetic joint infection (PJI). The thromboelastography (TEG) assay provides a comprehensive assessment of blood coagulation; therefore, it could be a promising test for PJI. This study aims to assess the value of TEG in diagnosing PJI and to determine the clinical significance of TEG in analysing reimplantation timing for second-stage revision. METHODS: From October 2017 to September 2020, 62 patients who underwent revision arthroplasty were prospectively included. PJI was defined by the 2011 Musculoskeletal Infection Society criteria, in which 23 patients were diagnosed with PJI (Group A), and the remaining 39 patients were included as having aseptic loosening (Group B). In group A, 17 patients completed a two-stage revision in our centre. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, and TEG parameters (clotting time, α-angle, MA [maximum amplitude], amplitude at 30 min, and thrombodynamic potential index) were measured preoperatively in all included patients. In addition, receiver operating characteristic curves were used to evaluate the diagnostic value of these biomarkers. RESULTS: ESR (area under curve [AUC], 0.953; sensitivity, 81.82; specificity, 94.87) performed best for PJI diagnosis, followed by MA (AUC, 0.895; sensitivity, 82.61; specificity, 97.44) and CRP (AUC, 0.893; sensitivity, 82.61; specificity, 94.74). When these biomarkers were combined in pairs, the diagnostic value improved compared with any individual biomarker. The overall success rate of the two-stage revision was 100%. Furthermore, ESR and MA were valuable in determining the time of reimplantation, and their values all decreased below the cut-off values before reimplantation. CONCLUSION: TEG could be a promising test in assisting PJI diagnosis, and a useful tool in judging the proper timing of reimplantation.