Calcipotriol suppresses GPX4-mediated ferroptosis in OA chondrocytes by blocking the TGF-ß1 pathway.

Globally, tens of millions of individuals experience osteoarthritis (OA), a degenerative joint condition for which a definitive cure is currently lacking. This condition is characterized by joint inflammation and the progressive deterioration of articular cartilage. In this study, western blotting, quantitative reverse-transcription polymerase chain reaction, and immunofluorescence analysis were performed to elucidate the molecular mechanisms by which calcipotriol alleviates chondrocyte ferroptosis. The effect of calcipotriol on reactive oxygen species and lipid peroxidation levels in chondrocytes was assessed using dihydroethidium staining and the fluorescent dye BODIPY. To replicate OA, the destabilized medial meniscus model was employed, followed by the injection of calcipotriol into the knee articular cavity. Morphological analysis was conducted through hematoxylin and eosin staining, safranin O-Fast green staining, and micro-computed tomography analysis. Immunohistochemical analysis was performed to validate the effect of calcipotriol in vivo. Our results demonstrate that the expression of SOX9, col2a1, and Aggrecan, as well as MMP13 and ADAMTS5 protein expression levels, decrease upon treatment with calcipotriol in interleukin-1ß stimulated chondrocytes. Despite these promising outcomes, the exact mechanism underlying calcipotriol's therapeutic effect on OA remains uncertain. We discovered that calcipotriol inhibits chondrocyte GPX4-mediated ferroptosis by suppressing the expression of transforming growth factor-ß1. Furthermore, our study established an in vivo model of OA using rats with medial meniscus instability. Our experiments on rats with OA revealed that intra-articular calcipotriol injection significantly reduces cartilage degradation caused by the disease. Our findings suggest that calcipotriol can mitigate OA by impeding GPX4-mediated ferroptosis of chondrocytes, achieved through the suppression of the TGF-ß1 pathway.

Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling in cartilage.

Osteoarthritis (OA) is a widespread chronic degenerative joint disease characterized by the degeneration of articular cartilage or inflamed joints. Our findings indicated that treatment with artemisinin (AT) downregulates the protein levels of MMP3, MMP13, and ADAMTS5, which are cartilage degradation-related proteins in OA, and inhibits the expression of inflammatory factors in interleukin-1ß (IL-1ß)-stimulated chondrocytes. However, the mechanism of the role of AT in OA remains unclear. Here, we performed gene sequencing and bioinformatics analysis in control, OA, and OA + AT groups to demonstrate that several mRNA candidates were enriched in the PI3K/AKT/mTOR signaling pathway, and TNFSF11 was significantly downregulated after AT treatment. TNFSF11 was downregulated in the OA + AT group, whereas it was upregulated in rat OA tissues and OA chondrocytes. Therefore, we confirmed that TNFSF11 was the target gene of AT. In addition, our study revealed that AT relieved cartilage degradation and defection by activating mitochondrial autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway in IL-1ß-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. Injecting AT into the knee joints of OA rat alleviated surgical resection-induced cartilage destruction. Thus, these findings revealed that AT relieves OA by activating mitochondrial autophagy by reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling.

The effects of Peptide Mel4-coated titanium plates on infection rabbits after internal fixation of open fractures.

INTRODUCTION: Infection after internal fixation surgery is an orthopedic serious complication which affect the fracture healing. The primary objective of this study was to verify the effects of a Peptide Mel4-coated titanium plate applied in the treatment of infection after internal fixation of open fracture. MATERIALS AND METHODS: Eighty-eight rabbits were intravenously inoculated with Staphylococcus aureus or Pseudomonas aeruginosa suspensions. Bacterial cultures were obtained from titanium plates at 1st, 3rd, 5th, 7th and 9th days. Blood samples were collected at 1st, 3rd, 5th, 7th and 9th days after the infection. RESULTS: Mel4-coated titanium plates have significant inhibitory effects on Staphylococcus aureus and Pseudomonas aeruginosa (P < 0.05), and there are significant differences in serum IL-1 and TNF-α levels (P < 0.05). CONCLUSION: We suggest that the use of Mel4-coated titanium plates may be a promising way to control postoperative infection of open fracture in vivo.

The IL-6 rs12700386 polymorphism is associated with an increased risk of developing osteoarthritis in the knee in the Chinese Han population: a case-control study.

BACKGROUND: This case-control study aims to examine the association between the Interleukin-6 (IL-6) rs12700386 polymorphism and the increased risk of developing osteoarthritis (OA) in the knee in the Chinese Han population. METHODS: We extracted DNA from 763 subjects (352 OA patients and 411 healthy controls). The relative expression levels of IL-6 in blood samples of patients with knee OA was determined by quantitative reverse transcription PCR (qRT-PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene polymorphism. RESULTS: We found that the IL-6 polymorphism rs12700386 enhanced patient susceptibility to developing knee OA. Based on a subgroup analysis, the risk of developing knee OA was elevated in smokers, drinkers, and subjects ≥55 years old or with BMI ≥ 25 kg/m2. The combination of smoking, drinking, and having the rs12700386 genotype led to an increase in the risk of developing knee OA, indicating that an underlying interaction between gene and environment exists. The rs12700386 genotype was found to be correlated with an increase in IL-6 expression. We also found that IL-6 levels were significantly higher in the CC genotype compared to the GG genotype carriers in OA patients. CONCLUSION: These data suggest that the rs12700386 polymorphism in the IL-6 gene leads to an increase in the risk of knee OA in Chinese Han individuals.

A functional polymorphism in the paired basic amino acid-cleaving enzyme 4 gene confers osteoarthritis risk in a population of Eastern China.

Paired basic amino acid-cleaving enzyme 4 (PACE4), a proprotein convertase, is involved in the activation of aggrecanases (ADAMTS-4 and ADAMTS-5) in osteoarthritic and cytokine-stimulated cartilage. Activated aggrecanases cause aggrecan degradation and thus, contribute to osteoarthritis (OA). In this study, we investigated the association between PACE4 gene polymorphisms and OA risk. One single-nucleotide polymorphism (rs4965833) in the PACE4 gene was genotyped in 432 OA patients and 523 healthy controls using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expression of PACE4 in blood samples from 90 OA patients (30 for each genotype). The relative expression level of PACE4 mRNA was higher in the GG genotype as compared to the AA/AG group. Moreover, the PACE4 rs4965833 polymorphism was associated with increased risk of OA, especially among individuals aged ≥55 years and with a body mass index ≥25. There was no significant association between the PACE4 rs4965833 polymorphism and clinical parameters of OA patients, such as erythrocyte sedimentation rate, C-reactive protein, Visual Analog Scale for pain and Lequesne's index. In conclusion, the rs4965833 polymorphism in the 3'-UTR of PACE4 is associated with OA susceptibility.

Variations of Wnt/ß-catenin pathway-related genes in susceptibility to knee osteoarthritis: A three-centre case-control study.

Excessive activation of the Wnt signalling pathway in the articular cartilage is demonstrated to be related to the onset and severity of osteoarthritis (OA). However, few studies have investigated the association between variants in Wnt-pathway-related genes and the risk of OA by searching Pubmed and EMBASE. Totally, 471 knee OA patients and 532 controls were recruited from three hospitals to evaluate the associations of five genetic variants (rs61735963, rs2908004, rs10795550, rs1799986 and rs1127379) with the risk of knee OA. These polymorphisms were genotyped through polymerase chain reaction and Sanger sequencing. Genetic risk scores (GRSs) were calculated to evaluate the combined effect of these genetic variants. No significant association was found between OA risk and polymorphisms (rs61735963, rs10795550 or rs1127379). However, WNT16 rs2908004 polymorphism was correlated with a decreased risk of OA, especially among females, smokers, non-drinkers and individuals with age < 60 years or BMI ≥ 25. This SNP was also associated with Kellgren-Lawrence grade and CRP. Similarly, LRP1 rs1799986 polymorphism decreased the risk of OA among males, smokers, drinkers and individuals with age < 60 years or BMI ≥ 25. TT genotype was more frequent in the group of VAS ≥ 6 versus VAS < 6. A low GRS was positively correlated with a decreased risk of OA. In addition, rs2908004 or rs1799986 polymorphism reduces the expression of WNT16 or LRP1. In conclusion, two SNPs (rs2908004 and rs1799986) are associated with the decreased risk of OA by regulating the Wnt pathway.

The Combined Use of Tea Polyphenols and Lactobacillus Plantarum ST8SH Bacteriocin in a Rabbit Model of Infection Following Femoral Fracture with Internal Fixation.

BACKGROUND Worldwide, the increasing use of antibiotics has resulted in antimicrobial resistance, leading to studies to find alternative antimicrobial treatments. Tea polyphenols have antibacterial properties. Bacteriocins produced by probiotic lactobacilli can inhibit Gram-positive bacteria. This study used a rabbit model of infection, following femoral fracture with internal fixation, to evaluate the efficacy of the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin. MATERIAL AND METHODS Twenty-four New Zealand White rabbits underwent femoral fracture, internal fixation, and insertion of a mini-titanium implant, and were inoculated intravenously with suspensions of Staphylococcal bacteria. Four treatment groups included group A, injected with tea polyphenols and bacteriocins (N=6); group B, injected with cefradine and bacteriocins (N=6); group C, injected with tea polyphenols and cefradine (N=6); and group D (controls), injected with saline (N=6). Blood samples were collected at 1, 6, 12, 24, and 48 hours after the injection of bacteriocins. Biofilms that formed on the mini-titanium implant were studied by fluorescence microscopy. Serum levels of level of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS The combination of tea polyphenols and bacteriocins (group A) had a significant inhibitory effect on Staphylococcus aureus (P<0.05) and significant differences in serum levels of IL-8, TNF-α, and IL-6 levels in serum (P<0.05) when compared with groups, B, C, and D. CONCLUSIONS In a rabbit model of femoral fracture with internal fixation, the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin effectively controlled Staphylococcus aureus infection.

Comparison of 2 Different Fixation Implants for Operative Treatment of Mid-Shaft Clavicle Fractures: A Retrospective Study.

BACKGROUND This retrospective analysis was designed to compare the outcomes of mid-shaft clavicle fracture operative treatment using bridge combined fixation system (BCFS) versus clavicular locking plate (CLP). MATERIAL AND METHODS Operative surgeries performed between January 2016 and July 2018 were included in the analysis. The surgical internal fixation implants were chosen according to surgeon preference and the choice of patients between the BCFS and CLP. Functional outcomes, fracture union, complications, pain, and patient satisfaction post-operation were assessed at a follow-up of 12 to 24 months. RESULTS Two hundred and seventeen (217) patients, aged 21-79 years, were operated, 87 using BCFS and 130 using CLP. The operation time of the BCFS group was significantly less than the CLP group (P<0.01). We also found that BCFS group had higher degree of satisfaction (100% vs. 97%, P<0.03) and less VAS scale (0.25±0.18 vs. 0.35±0.21, P<0.001) compared with the CLP group, but the significance could only be obtained during the follow-up at 3 months after surgery. No significant differences were observed between the 2 groups when compared for fracture unions, functional scores, or complications. CONCLUSIONS BCFS significantly reduced the operation time when compared with CLP. No significant differences were observed for functional outcomes, including fracture union and complications, and there was less pain and higher patient satisfaction. Both methods appeared to be safe in terms of complications. However, the effectiveness and safety of BCFS in treating comminuted multi-fragmentary mid-shaft clavicle fractures (AO/OTA 15-2C classification) need further confirmation.

Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population.

INTRODUCTION: The aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population. MATERIALS AND METHODS: We studied IL-12A rs2243115 T/G and IL-12B rs3212227 A/C polymorphisms in 615 RA patients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48-Plex SNPscan™ Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RA patients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians. RESULTS: A significantly increased risk for RA associated with the IL-12A rs2243115 GG (GG versus TT: OR=4.81, 95% CI 1.33-17.36, P=0.017; and GG versus TG+TT: OR=4.55, 95% CI 1.27-16.36, P=0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12B rs3212227 AC (AC versus AA) and AC+CC (AC+CC versus AA) genotypes were evident among older patients (OR=1.48, 95% CI 1.06-2.06, P=0.020), RF positive patients (OR=1.35, 95% CI 1.04-1.75, P=0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR=1.53, 95% CI 1.11-2.10, P=0.009). The plasma level of IL-12 was significantly higher in RA patients (P<0.001). IL-12 plasma level of IL-12A rs2243115 TT (P<0.001) and IL-12B rs3212227 C allele (P<0.001) were significantly higher in RA patients than controls respectively. The plasma level of IL-12 of RF positive RA patients was significantly higher than RF negative patients (P=0.008), especially in rs3212227 AC patients (P=0.01). CONCLUSIONS: These findings suggested that the functional single nucleotide polymorphism (SNP) IL-12A rs2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12B rs3212227 AC and AC+CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12A rs2243115 T/G and IL-12B rs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA.

Current Status and Influencing Factors of Secondary Traumatic Stress in Emergency and Intensive Care nurses:A Cross-Sectional Analysis.

Objective: Secondary traumatic stress (STS) is stress caused by helping or wanting to help someone who has suffered a traumatic event. STS has adverse effects on nurses and their work, such as reduced career achievement, an increased staff turnover rate, inability to complete work, avoidance of contact with patients, mental exhaustion, negative emotions which seriously affect the quality of their work and life. The study to investigate secondary traumatic stress in emergency and intensive care nurses and analyze factors that influence it. Material and Methods: The study was a cross-sectional survey. Convenience sampling was used to select hospital emergency and intensive care department nurses (n=434) who met the inclusion and exclusion criteria from August to October 2021 to participate in this study. They provided demographic data and completed measures of secondary traumatic stress, emotional intelligence, anxiety and depression. Data analysis included independent samples t-tests, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis. Results: Almost one-third (30.7%) of participants were at moderate risk for Secondary Traumatic Stress Scale or above, with high average scores on measures of anxiety (GAD-7 average = 6.05 ± 4.13), and depression (PHQ-9 average = 6.35 ± 4.85). The results of multiple linear regression analysis showed that the average daily amount of sleep in the past week, the number of night shifts in the past month, emotional intelligence, anxiety, and depression influenced secondary traumatic stress, explaining 70.8% of the variance. Conclusion: The STS of emergency and intensive care nurses in Changzhou is at a high level. Sleep time, number of night shifts and emotional intelligence are related to secondary traumatic stress and anxiety and depression significantly predicted the degree of secondary traumatic stress. Nurses need to master effective treatment methods for secondary traumatic stress, to improve their work efficiency and nursing quality and ensure nursing safety.

Gossypol Acetic Acid alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, usually accompanied by degeneration of the articular cartilage, fibrosis, bone hyperplasia around the joint, and damage to the entire articular surface. Gossypol is a natural phenolic compound isolated from the seed of cotton plants, and gossypol acetic acid (GAA) is a medicinal form of Gossypol. Recently, various biological activities of GAA, including anti-inflammatory and anti-tumor effects, have been widely reported. However, its effect on chondrocytes in OA has yet to be determined. METHODS: In this study, we investigated the effect of GAA on ferroptosis in OA chondrocytes. The effect of GAA on the cell viability and cytotoxicity of chondrocytes in rat cells was investigated using CCK8. Western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescence staining were used to elucidate the molecular mechanisms and signaling pathways of GAA inhibition of ferroptosis in OA chondrocytes. The effect of GAA on reactive oxygen species (ROS) production and lipid peroxidation levels in chondrocytes was examined using dihydroethidium (DHE) staining and fluorescent dye BODIPY581/591 C11. in vivo, micro-CT imaging, hematoxylin and eosin staining, Safranin O-Fast staining, and immunohistochemistry were performed to evaluate the effects of GAA on OA cartilage. RESULTS: The results showed that GAA treatment regulated the expression of chondrocyte extracellular matrix (ECM) related factors, including ADAMTS5, MMP13, SOX9, Aggrecan, and COL1A2 and reduced the ROS and lipid peroxidation levels. Besides, Erastin could reverse the effects of GAA on chondrocytes. Similar to GAA, 5-AZA caused the reduction of ROS and lipid peroxidation levels and reversed the effect of IL-1ß on the expression of ECM-related factors in OA chondrocytes. The above results clarified that GAA alleviated the ferroptosis of chondrocytes in OA by inhibiting GPX4 methylation. CONCLUSION: Our findings revealed that GAA might be developed as a drug for treating OA clinically.

Neutrophil membrane-coated multifunctional biomimetic nanoparticles for spinal cord injuries.

Spinal cord injury (SCI) is one of the most complex diseases. After SCI, severe secondary injuries can cause intense inflammatory storms and oxidative stress responses, leading to extensive neuronal apoptosis. Effective regulation of inflammation and oxidative stress after SCI remains an unresolved challenge. In this study, resveratrol-loaded nanoparticles coated with neutrophil membranes (NMR) were prepared using the emulsion-solvent evaporation method and membrane encapsulation technology. Multifunctional biomimetic nanoparticles retain neutrophil membrane-related receptors and possess a strong adsorption capacity for inflammatory factors. As a drug carrier, NMR can sustainably release resveratrol for >72 h. Moreover, co-culture studies in vitro show that the NMR help regulate macrophage polarization to relieve inflammatory response, reduce intracellular reactive oxygen species by approximately 50%, and improve mitochondrial membrane potential to alleviate oxidative stress. After injecting NMR into the injury site, it reduces early apoptosis, inhibit scar formation, and promote neural network recovery to improve motor function. This study demonstrates the anti-inflammatory, antioxidant, and neuroprotective effects of NMR, thus providing a novel therapeutic strategy for SCI.

Increased serum levels and chondrocyte expression of nesfatin-1 in patients with osteoarthritis and its relation with BMI, hsCRP, and IL-18.

BACKGROUND: Adipokines have been proved to relate with osteoarthritis (OA). As a recently discovered adipokine, nesfatin-1 relationship with OA has not been reported. AIM: To determine the levels of nesfatin-1 in serum and synovial fluid (SF) from patients with and without OA; to examine the correlation between nesfatin-1 levels and high sensitivity C-reactive protein (hsCRP), Type IIA Collagen N Propeptide (PIIANP), and IL-18 (interleukin-18) levels in serum or synovial fluid. METHODS: Serum and SF were collected from knee OA patients and healthy persons, respectively. Five articular tissues were obtained during TKR for immunohistochemistry (IHC). Nesfatin-1 levels, hsCRP, PIIANP, and IL-18 in serum and SF were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Nesfatin-1 gene was expressed in OA-affected articular cartilage. OA serum contained significantly higher levels of nesfatin-1, as compared to serum from healthy controls (P < 0.05), and nesfatin-1 levels in OA serum exceeded those in paired SF samples (P < 0.001). Significant correlation was found between serum nesfatin-1 and hsCRP levels in OA patients (r = 0.593, P = 0.00005) and also synovial nesfatin-1 and IL-18 levels (r = 0.560, P = 0.0017). CONCLUSION: Nesfatin-1 is present in articular tissues and may contribute to the physiopathologic changes in OA. Nesfatin-1, accompanied with hsCRP and IL-18, could be new molecular makers to speculate OA progression.

Do we really need closed-suction drainage in total hip arthroplasty? A meta-analysis.

PURPOSE: The clinical use of closed-suction drainage, which aims to reduce postoperative wound haematomas and infection, is common. This study was performed to determine whether closed-suction drainage is safe and effective in promoting wound healing and reducing blood loss and other complications compared with no-drainage in total hip arthroplasty. METHODS: The literature search was based on PubMed, the Cochrane Library, MEDLINE, and EMBASE. The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group, and then analysed using RevMan 5.0. Twenty randomised controlled trials involving 3,186 patients were included in our analysis. RESULTS: The results of our meta-analysis indicate that closed-suction drainage reduces the requirement for dressing reinforcement, but increases the rate of homologous blood transfusion. No significant difference was observed in the incidence of infection, blood loss, changes in haemoglobin and haematocrit, functional assessment, or other complications when the drainage group was compared with the no-drainage group. CONCLUSIONS: Our results of the comparison between closed-suction drainage and no drainage in THA have indicated that the routine use of closed-suction drainage for elective total hip arthroplasty may be of more harm than benefit.

Do we really need tranexamic acid in total hip arthroplasty? A meta-analysis of nineteen randomized controlled trials.

BACKGROUND: Studies have shown that tranexamic acid reduces blood loss and transfusion need in patients undergoing total hip arthroplasty. However, no to date, no study has been large enough to determine definitively whether the drug is safe and effective. We examined whether intravenous tranexamic acid, when compared with placebo, was safe and effective in total hip arthroplasty. METHODS: The literature search was conducted using the PubMed, Cochrane Library, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. Data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. Ultimately, 19 randomized controlled trials involving 1,030 patients were included. RESULTS: The use of tranexamic acid significantly reduced total blood loss by a mean of 305.27 mL [95 % confidence interval (CI) -397.66 to -212.89, p < 0.001], intraoperative blood loss by a mean of 86.33 mL(95 % CI -152.29 to -20.37, p = 0.01), postoperative blood loss by a mean of 176.79 mL (95 % CI -236.78 to -116.39, p < 0.001), and "hidden" blood loss by a mean of 152.70 mL (95 % CI -187.98 to -117.42, p < 0.001), resulting in a meaningful reduction in the proportion of patients requiring blood transfusion (odds ratio 0.28, 95 % CI 0.19 to 0.42, p < 0.001). There was no significant difference in occurrence of deep vein thrombosis, pulmonary embolism, or other complications among the study groups, or cost or hospitalization duration. CONCLUSIONS: The data from this meta-analysis indicate that intravenous tranexamic acid may reduce blood loss and transfusion need in patients undergoing total hip arthroplasty without increasing the risk of complications. However, high-quality randomized controlled trials are required to validate the results.

Isorhynchophylline alleviates cartilage degeneration in osteoarthritis by activating autophagy of chondrocytes.

CONTEXT: Osteoarthritis is a common degenerative disease, the cause of it is still unknown, and the treatment mainly focuses on improving symptoms. Studies have found that Isorhynchophylline (Isorhy) has antioxidant, anti-inflammatory, antiproliferative and neuroprotective effects. OBJECTIVE: This study investigates the role and mechanism of Isorhy in OA. METHODS: The destabilized medial meniscus model was used to mimic OA. Fifteen male Sprague Dawley rats were partitioned into three portions: Normal group, OA group (surgery; normal saline treatment) and OA + Isorhy group (surgery; 50 µM Isorhy treatment) were performed on the first day of every week from the 5th to the 8th week after surgery. After 4 weeks of drug treatment, the rats have been processed without debridement of the knee specimens and fixed using 4% paraformaldehyde for two days. The morphological analysis was performed by H&E, Safranin O-Fast green staining and micro-CT analysis. The specimens were researched employing Micro-CT. In the part of the aggregate methods that were evaluated by qRT-PCR and western blot of the following proteins LC3II/LC3I, Beclin-1, ATG5, ATG7, MMP3 andMMP13. Akt/PI3K signaling related proteins (p-AKT, AKT, p-PI3K, PI3K, p-mTOR, mTOR) were detected by Western blot. BECLIN1 and MMP3 were detected by Immunofluorescence assay. RESULTS: In this present research, it was proved that autophagy-related and cartilage matrix-related proteins in osteoarthritis could be regulated by Isorhynchophylline treatment. The transcriptome sequencing results suggested the regulation was closely associated with PI3K/AKT/mTOR pathway, thereby alleviating osteoarticular inflammation. In-depth study showed that Isorhy could also affect OA in rat OA models, that was indicated by H&E, Safranin O-Fast green staining, and also micro-CT analysis. CONCLUSION: Our findings indicated that Isorhy could be regarded as a prospective candidate for OA treatment.

Resistin targets TAZ to promote osteogenic differentiation through PI3K/AKT/mTOR pathway.

Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) contributes significantly to the regeneration of bone defects. Resistin, an adipose tissue-specific secretory factor, has been shown to involve many different functions, including metabolism, inflammation, cancer, and bone remodeling. However, the effects and mechanisms of resistin on OD of BMSCs remain unclear. Herein, we demonstrated that resistin was highly expressed in BMSCs with OD. Upregulation of resistin contributed to the progression of OD of BMSCs by activating PI3K/AKT/mTOR signaling pathway. In addition, resistin facilitated OD by targeting transcriptional co-activator with PDZ-binding motif (TAZ). In a rat femoral condyle bone defect model, local injection of resistin significantly promoted bone repair and improved bone formation. This work contributes to better understanding the mechanism of resistin directly involved in the OD and might provide a new therapeutic strategy for bone defect regeneration.

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study.

BACKGROUND: Despite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal. OBJECTIVE: The aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation. METHODS: We performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery. RESULTS: A total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively. CONCLUSION: Pharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.

CK1ε drives osteogenic differentiation of bone marrow mesenchymal stem cells via activating Wnt/ß-catenin pathway.

The treatment of bone defects is a difficult problem in orthopedics. At present, the treatment mainly relies on autologous or allogeneic bone transplantation, which may lead to some complications such as foreign body rejection, local infection, pain, or numbness at the bone donor site. Local injection of conservative therapy to treat bone defects is one of the research hotspots at present. Bone marrow mesenchymal stem cells (BMSCs) can self-renew, significantly proliferate, and differentiate into various types of cells. Although it has been reported that CK1ε could mediate the Wnt/ß-catenin pathway, leading to the development of the diseases, whether CK1ε plays a role in bone regeneration through the Wnt/ß-catenin pathway has rarely been reported. The purpose of this study was to investigate whether CK1ε was involved in the osteogenic differentiation (OD) of BMSCs through the Wnt/ß-catenin pathway and explore the mechanism. We used quantitative reverse transcription-polymerase chain reaction (qRT-qPCR), Western blots, immunofluorescence, alkaline phosphatase, and alizarin red staining to detect the effect of CK1ε on the OD of BMSCs and the Wnt/ß-catenin signaling pathway. CK1ε was highly expressed in BMSCs with OD, and our study further demonstrated that CK1ε might promote the OD of BMSCs by activating DLV2 phosphorylation, initiating Wnt signaling downstream, and activating ß-catenin nuclear transfer. In addition, by locally injecting a CK1ε-carrying adeno-associated virus (AAV5- CK1ε) into a femoral condyle defect rat model, the overexpression of CK1ε significantly promoted bone repair. Our data show that CK1ε was involved in the regulation of OD by mediating Wnt/ß-catenin. This may provide a new strategy for the treatment of bone defects.

Adipokines regulate mesenchymal stem cell osteogenic differentiation.

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.