Advances in the study of plant-derived extracellular vesicles in the skeletal muscle system.

Plant-derived extracellular vesicles (PDEV) constitute nanoscale entities comprising lipids, proteins, nucleic acids and various components enveloped by the lipid bilayers of plant cells. These vesicles play a crucial role in facilitating substance and information transfer not only between plant cells but also across different species. Owing to its safety, stability, and the abundance of raw materials, this substance has found extensive utilization in recent years within research endeavors aimed at treating various diseases. This article provides an overview of the pathways and biological characteristics of PDEV, along with the prevalent methods employed for its isolation, purification, and storage. Furthermore, we comprehensively outline the therapeutic implications of diverse sources of PDEV in musculoskeletal system disorders. Additionally, we explore the utilization of PDEV as platforms for engineering drug carriers, aiming to delve deeper into the significance and potential contributions of PDEV in the realm of the musculoskeletal system.

Causal associations between sarcopenia-related traits and intervertebral disc degeneration: a two-sample mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. METHODS: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. RESULTS: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). CONCLUSION: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice.

Lycopene inhibits IL-1ß-induced inflammation in mouse chondrocytes and mediates murine osteoarthritis.

Osteoarthritis (OA) is a common chronic degenerative condition in the elderly, in which inflammation plays a key role in disease pathology. Lycopene (Lye), a member of the carotenoid family, has been reported to have anti-inflammatory effects. The purpose of this study was to investigate the effect of Lye on the inflammation of chondrocytes and the mouse OA model. Chondrocytes were treated with interleukin (IL)-1ß, and the mouse OA model was induced by the surgical destabilization of the medial meniscus (DMM). The results showed that Lye could inhibit the expression of inflammatory factors and alleviate the degradation of extracellular matrix (ECM). Additionally, Lye could activate the Nrf2/HO-1 pathway and reverse the activations of NF-κB and STAT3 signal pathway induced by IL-1ß, suggesting that its anti-inflammatory effect may be mediated via these pathways. The animal experiments showed that Lye could decrease the Osteoarthritis Research Society International (OARSI) scores of the knee, indicating that it could inhibit the occurrence and development of OA in mouse. Overall, our results indicated that Lye might be used as a novel drug for OA treatment.

Activating Nrf2 signalling alleviates osteoarthritis development by inhibiting inflammasome activation.

Osteoarthritis (OA), which is characterized by proliferation of subchondral bone and the degeneration of articular cartilage, is the most prevalent human arthritis. Nod-like receptor pyrin domain 3 (NLRP3) inflammasome is a hot spot in recent year and has been reported to be associated with OA synovial inflammation. However, there are few studies on NLRP3 inflammasome in chondrocyte. Licochalcone A (Lico A), a compound extracted from Glycyrrhiza species, has various biological effects such as anti-inflammation, anti-apoptotic, anti-cancer and anti-oxidation. In this study, we investigated the protective effect of Lico A on chondrocytes stimulated by lipopolysaccharide (LPS) and surgically induced OA models. In vitro, Lico A could reduce the expression of NLRP3, apoptosis-associated speck-like protein (ASC), Gasdermin D (GSDMD), caspase-1, interleukin-1beta (IL-1ß) and IL-18, which indicated that Lico A attenuates LPS-induced chondrocytes pyroptosis. In addition, Lico A ameliorates the degradation of extracellular matrix (ECM) by enhancing the expression of aggrecan and collagen-II. Meanwhile, we found that Lico A inhibits NLRP3 inflammasome via nuclear factor erythroid-2-related factor 2 (Nrf2)/haeme oxygenase-1(HO-1)/nuclear factor kappa-B (NF-κB) axis. And the Nrf2 small interfering RNA (siRNA) could reverse the anti-pyroptosis effects of Lico A in mouse OA chondrocytes. In vivo, Lico A mitigates progression OA in a mouse model and reduces OA Research Society International (OARSI) scores. Thus, Lico A may have therapeutic potential in OA.

Astilbin prevents osteoarthritis development through the TLR4/MD-2 pathway.

Osteoarthritis has become one of the main diseases affecting the life of many elderly people with high incidence of disability, and local chronic inflammation in the joint cavity is the most crucial pathological feature of osteoarthritis. Astilbin is the main active component in a variety of natural plants such as Hypericum perforatum and Sarcandra glabra, which possess antioxidant and anti-inflammatory effects. At present, there is no study about the protective effect of Astilbin for osteoarthritis. The purpose of this study was to investigate the effect of Astilbin in human OA chondrocytes and mouse OA model, which was established by surgery-mediated destabilization of the medial meniscus (DMM). In vitro, we found that Astilbin pre-treatment inhibited lipopolysaccharide (LPS)-induced overproduction of inflammation-correlated cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and suppressed overexpression of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Astilbin, on the other hand, prevented the LPS-induced degradation of extracellular matrix (ECM) by down-regulating MMP13 (matrix metalloproteinases 13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5). Moreover, by inhibiting the formation of the TLR4/MD-2/LPS complex, Astilbin blocked LPS-induced activation of TLR4/NF-κB signalling cascade. In vivo, Astilbin showed the chondro-protective effect in the surgical-induced OA mouse models. In conclusion, our findings provided evidence that develops Astilbin as a potential therapeutic drug for OA patients.

Downregulating STAT1/caspase-3 signaling with fludarabine to alleviate progression in a rat model of steroid-induced avascular necrosis of the femoral head.

Steroid-induced avascular necrosis of the femoral head (SANFH) is mainly induced by glucocorticoids. Fludarabine (Flu) is a specific signal transducer and activator of transcription 1 (STAT1) inhibitor. In this study, we investigated the effect of Flu on SANFH and the role played by the STAT1/caspase-3 signaling pathway. Sprague-Dawley rats were divided into control, SANFH, and Flu-treated SANFH groups. Femoral head tissues were collected for hematoxylin-eosin (H&E) staining and Western blot analysis. The latter was used to measure the levels of stat1, phospho-stat1, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, Bax, cytochrome C, Bak, B-cell lymphoma-extra large, and B-cell lymphoma-2 protein expression. The results showed that Flu regulates protein expression in dexamethasone (Dex)-induced SANFH. H&E staining showed a decrease in the ratio of empty lacunae induced by Dex. Taken together, our study demonstrated the involvement of the STAT1/caspase-3 signaling pathway in SANFH and the potential of Flu as a therapeutic agent for patients with SANFH.

Investigating the causal relationship between thyroid dysfunction diseases and osteoporosis: a two-sample Mendelian randomization analysis.

The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.

Candida parapsilosis-Caused Arthritis with Rice Body Formation: A Case Presentation and Literature Review.

A 68-year-old male patient came to the orthopedics department because of swelling and pain in his left shoulder joint. He received more than 15 intraarticular steroid injections in the shoulder joint at a local private hospital. MRI showed that the synovial membrane of the joint capsule was thickened and swollen, and there were extensive "rice body-like" low T2 signal shadows filling. Arthroscopic removal of rice bodies and subtotal bursectomy were performed. The observation channel was placed through the posterior approach, and a large amount of rice bodies in yellow bursa fluid were observed to flow out. Rice bodies with a diameter of approximately 1-5 mm filled the joint cavity were seen in the observation channel. The histopathological examination of the rice body showed that it was mainly composed of fibrin without a clear tissue structure. Bacterial and fungal cultures of synovial fluid suggested Candida parapsilosis infection, so the patient received antifungal treatment. However, the shoulder swelled again after three weeks, MRI revealed that there was significant fluid accumulation in the subacromial-subdeltoid region with necrotic synovial tissue floating and ultrasound examination showed joint cavity effusion, synovial hyperplasia, and some synovium looked like "floating weeds". After 2 weeks, there were recurrent rice bodies in the articular cavity. Arthroscopic surgery was performed again to clean the joint and a catheter was placed for irrigation and drainage, and a large amount of necrotic synovial tissue floating as seen in ultrasound. Finally, patient received sensitive antifungal treatment and did not relapse within 6 months. During the recurrence in the current case, we recorded the process of rice body formation, which has for the first time been reported.

Establishment and validation of nomogram models for overall survival and cancer-specific survival in spindle cell sarcoma patients.

Spindle cell sarcoma (SCS) is rare in clinical practice. The objective of this study was to establish nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. The data of patients with SCS between 2004 and 2020 were extracted from the SEER database and randomly allocated to a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to screen for independent risk factors for both overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate Cox analysis. Then, we validated the nomograms by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, Kaplan‒Meier curves and log-rank tests were applied to compare patients with SCS at three different levels and in different treatment groups. A total of 1369 patients with SCS were included and randomly allocated to a training cohort (n = 1008, 70%) and a validation cohort (n = 430, 30%). Age, stage, grade, tumour location, surgery, radiation and diagnosis year were found to be independent prognostic factors for OS by Cox regression analysis, while age, stage, grade, tumour location and surgery were found to be independent prognostic factors for CSS. The nomogram models were established based on the results of multivariate Cox analysis for both OS and CSS. The C-indices of the OS model were 0.76 and 0.77 in the training and validation groups, respectively, while they were 0.76 and 0.78 for CSS, respectively. For OS, the 3- and 5-year AUCs were 0.801 and 0.798, respectively, in the training cohort and 0.827 and 0.799, respectively, in the validation cohort; for CSS, they were 0.809 and 0.786, respectively, in the training cohort and 0.831 and 0.801, respectively, in the validation cohort. Calibration curves revealed high consistency in both OS and CSS between the observed survival and the predicted survival. In addition, DCA was used to analyse the clinical practicality of the OS and CSS nomogram models and revealed that they had good net benefits. Surgery remains the main treatment method for SCS patients. The two nomograms we established are expected to accurately predict the personalized prognosis of SCS patients and may be useful for clinical decision-making.

The Tight-Rope Technique versus Clavicular Hook Plate for Treatment of Acute Acromioclavicular Joint Dislocation: A Systematic Review and Meta-Analysis.

Objective: The efficacy of the tight-rope (TR) technique and clavicular hook plate (CHP) for the treatment of acute acromioclavicular (AC) joint dislocation is controversial. This meta-analysis aimed to evaluate which method is more appropriate for the treatment of acute AC joint dislocation. Methods: We systematically searched the PubMed, EMBASE, Scopus, ISI Web of Science, Chinese VIP Database, and Chinese Wan-Fang databases from inception to January 2018 using the search term "acromioclavicular joint dislocation AND hook plate." All prospective and retrospective controlled trials that had compared functional scores, pain scores, reduction loss rates, coracoclavicular (CC) distances, and complications between TR and CHP for acute AC joint dislocation were identified. A total of 13 of 587 studies with 732 patients were included. TR was preferential to CHP for AC joint dislocation given its higher Constant-Murley score, lower Visual Analog Scale pain score, and comparable reduction loss rate and CC distance. Subgroup analyses of the surgical type of TR did not affect the outcome. Results: The TR technique appears to be associated with better functional recovery and less pain than CHP. In addition, it does not increase the risk of reduction loss, CC distance, or operation time. It is also not associated with other complications except the implant migration, and does not require removal of the internal fixation. Conclusions: Thus, our results indicated that for AC joint dislocation, the TR technique may be preferential.

Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis.

Osteoarthritis (OA) is one of the most common degenerative diseases, ultimately leading to long-term joint pain and severe articular malformation. Controlling local chronic inflammation is a crucial strategy for delaying OA development. Linarin is a natural flavonoid glycoside that is widely available in Compositae, Chrysanthemum indicum and Dendrocalamus and processes protective effects in several animal models. The purpose of our work was to study the protective effect of Linarin for OA. Cellular experiments data showed that Linarin suppressed lipopolysaccharide (LPS)-caused the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in chondrocyte. In addition, LPS-stimulated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide nitrate (iNOS) was decreased by Linarin pre-treatment. Together, Linarin prevented the catabiosis of extracellular matrix caused by LPS. For mechanism, Linarin inhibited the formation of Toll-like receptor 4 (TLR4) / myeloid differentiation protein-2 (MD-2) dipolymer complex and subsequently intervened NF-κB activation. Our mouse DMM model further clarified the protection of Linarin in vivo. In summary, our results suggested that Linarin may be a potential effective agent for OA.

The Protective Effect of Luteolin in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a frequently occurring type of nontraumatic osteonecrosis. A failure of the timely treatment can eventually result in the collapse of the subchondral bone structure. Luteolin (Lut), a compound extracted from Rhizoma Drynariae, is reported to possess multiple pharmacological properties including anticancer, antioxidant, antiapoptosis, and antiinflammatory properties. However, whether Lut has a protective effect on the development of GIONFH remains unclear. In this study, we evaluated the effect of Lut on Dexamethasone (Dex)-induced STAT1/caspase3 pathway in vitro and evaluated GIONFH model in vivo. In vitro, Lut inhibited the upregulation of Dex-induced phospho-STAT1, cleaved caspase9, and cleaved caspase3. In addition, Lut inhibited Dex-induced expression of Bax and cytochrome c and increased the expression of B cell lymphoma-2(Bcl-2). In vivo, Lut decreased the proportion of empty lacunae in rats with GIONFH. Taken together, these findings indicate that Lut may have therapeutic potential in the treatment of GIONFH. Further, this effect might be achieved by suppressing mitochondrial apoptosis of osteoblasts via inhibition of STAT1 activity.

Allicin inhibits osteoblast apoptosis and steroid-induced necrosis of femoral head progression by activating the PI3K/AKT pathway.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a major complication of long-term or excessive clinical use of glucocorticoids. Allicin is a classical ingredient extracted from garlic and has many functions such as anti-apoptosis and antibacterial effects. The purpose of this study was to investigate the effect and the mechanism of allicin on apoptosis of osteoblasts induced by dexamethasone (Dex) and SANFH in rats. In vitro, we performed CCK-8, western blotting, TUNEL and other experiments, and the results of these experiments showed that allicin could inhibit the Dex-induced abnormal expression of C-caspase3, C-caspase9, Bax, cytochrome C and Bcl-2 by activating the PI3K/AKT pathway. In vivo, the results of micro-CT, hematoxylin-eosin staining and immunohistochemical analysis suggested that allicin could effectively inhibit the progress of SANFH in rats. In summary, our experiments indicate that allicin is a potential drug for the treatment of SANFH.

The protective effect of myricitrin in osteoarthritis: An in vitro and in vivo study.

Osteoarthritis (OA) is a long-term, chronic, progressive joint condition caused by a pathology characterized by the deterioration of joint cartilage and proliferation of subchondral bone. Myricitrin (Myr) is a flavonoid compound extracted from myrica rubra with potent anti-inflammatory properties, as demonstrated in various studies. However, the mechanisms by which Myr plays a protective role in OA are not completely understood. In this study, the anti-inflammatory properties and potential mechanisms of Myr on mouse chondrocytes treated with interleukin (IL) -1beta (ß) were explored in vitro and the role of Myr in a mouse model of OA in vivo. The production of pro-inflammatory factors, such as IL-6, tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) and nitric oxide (NO) were assessed by enzyme linked immunosorbent assay (ELISA) and the Griess reaction. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Collagen-II, matrix metalloproteinase(MMP)-13, MMP-3, thrombospondin motifs 5(ADAMTS5), inhibitor ofnuclear factor kappa-B (IκB), p-IκB, p65, p-p65, c-jun-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 and p-p38 were quantified using Western blot analysis. In the present study, we found that Myr inhibited IL-1ß-induced production of NO and PGE2, expression of MMP-13, MMP-3 and ADAMTS5 and degradation of collagen-II in mouse chondrocytes. Mechanistically, Myr inhibited the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) treated with IL-1ß in mouse chondrocytes. In vivo, Myr decreased OA Research Society International (OARSI) scores in a surgically-induced mouse model of OA. These data suggest that Myr could be developed as a potential therapyfor OA.

Arthroscopic treatment of posterior instability of the shoulder with an associated reverse Hill-Sachs lesion using an iliac bone-block autograft.

Posterior dislocation of the shoulder is often accompanied by an impression fracture in the anterior surface of the humeral head, called a reverse Hill-Sachs injury. This bone defect can engage on the posterior glenoid rim, which can lead to recurrent instability and progressive joint destruction. We describe a new arthroscopic procedure that fills the reverse Hill-Sachs lesion with an iliac bone-block autograft and repairs the posterior articular capsule arthroscopically, which can stabilize the posterior shoulder. It avoids the need to detach the subscapularis tendon and can reduce the risks associated with open procedures. LEVEL OF EVIDENCE: V, technical note.

An arthroscopic technique for full-thickness rotator cuff repair by transposition of the long head of biceps.

Arthroscopic rotator cuff (RC) repair is now considered as an effective treatment for patients with symptomatic rotator cuff tears. We reported a new method for repairing a full-thickness RC tear by using the double-row technique with transposition of the long head of biceps (LHB). The novelty of this technique is using the long head of the biceps as an augmentation. The indication of this technique consists of two aspects including LHB lesions and RC tears. Three patients were enrolled. An ideal reconstruction of the anatomic footprint of the tendon and stabilization of glenohumeral joint was achieved after the double-row technique with the transposition of the long head of biceps. At 6-month postoperation, the mean VAS score was 1.23±0.15 and the mean Constant score was 88.00±9.17. Transposition of the long head of biceps is a choice for full-thickness RC tear. LEVEL OF EVIDENCE: IV, case series.

A technique combining "U" shape suture and shared tunneling to treat the posterior cruciate ligament rupture and posterior root tears of the medial meniscus.

BACKGROUND: The standard treatment of the posterior cruciate ligament (PCL) rupture accompanied with the posterior root of medial meniscus (PRMM) tears is controversial. Our research describes a minimally invasive technique for the PCL rupture accompanied with the PRMM tears. METHODS: We described a "U" shape suture and shared tunneling technique to treat the PCL rupture accompanied with PRMM tears. Three patients (ages 28, 42, and 59 years old) who underwent this surgery have been followed up for more than 1 year at most. The MRI was done, and the hospital for special surgery (HSS) score was adopted to evaluate the clinical effect. Firstly, we built both femoral and tibial bone tunnels for the PCL reconstruction. Secondly, we used the suture hook to pass the suture line through the PRMM. Thirdly, we passed the prepared tendon through the bone tunnel and fixed the prepared tendon by an endobutton plate and an interference screw (Smith & Nephew) respectively on the side of the femur and tibia. At last, we used an endobutton plate (Smith & Nephew) outside the tibial bone tunnel to fix the PRMM. RESULTS: These three patients did not show any complications. At 1 year after the operation, we found good knee stability, negative posterior drawer test, and normal range of motion compared with the contralateral knee joint. The MRI also showed a good union of the PRMM and PCL. The hospital for special surgery (HSS) score was 90 points. CONCLUSIONS: With an ideal therapeutic effect, this technique is worthy to be promoted for patients with the PCL rupture and PRMM tears.

Isofraxidin inhibits interleukin-1ß induced inflammatory response in human osteoarthritis chondrocytes.

Osteoarthritis (OA) is the most prevalent disease of knee especially in the aged people. Isofraxidin (IF) is a coumarin compound refined from traditional Chinese medicines with potential anti-inflammatory ability. This study aimed to evaluate protective anti-inflammatory effects of IF in human OA chondrocytes. The chondrocytes were isolated from OA patients and pretreated with IF before treatment with IL-1ß. The results showed that IF blocked IL-1ß-stimulated production of NO and PGE2. In addition, IF inhibited the expression of COX-2, iNOs, MMP-1, MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5, and increased the levels of aggrecan and collagen-II. Mechanistically, IF suppressed IL-1ß-induced IκB-α degradation and NF-κB activation. In conclusion, our results demonstrate that IF inhibits inflammation in OA via the regulation of NF-κB signaling, and suggest that IF may be a potential therapeutic agent for OA.